NINTEDANIB and Malignant Pleural Mesothelioma

Posted on December 6, 2017 by Ellie and Lisa

The drug Offev or Nintedanib, also known as BIBF 1120, is currently showing promise in treating patients with malignant pleural mesothelioma. Nintedanib is classified as an oral triple angiokinase inhibitor. Nintedanib targets receptors that play a role in tumor growth and development of metastasis in malignant pleural mesothelioma. The cancer cells release growth factors, bind to activate growth factor. In order for the tumor to spread or metastasize angiogenesis takes place. Angiogenesis is blood vessel formation. The tumor needs new blood vessels to grow. Nintedanib uses anti-angiogenic strategy that is different from other approved treatments. Nintedanib is a small molecule that targets three receptors known to be involved in angiogenesis.

The pathways that the drug uses are a potent intracellular inhibitor of tyrosine kinases. It targets platelet derived growth factor receptors (PDGFR) a and B, vascular endothelial growth factor receptor VEGFR 1,2, and 3. FGFR 1,2 1nd 3 fibroblast growth factor receptors.

The LUME-Meso phase 11 trial in patients, showed patients given this drug by mouth plus the standard chemotherapy of pemetrexed and cisplatin had significantly longer progression –free survival than those treated with a placebo and the standard therapy. Overall survival was also longer with Nintedanib (18.3 vs. 14.5 months.)

The company Boehringer Ingelheim applied and was granted approval as an orphan drug status for the drug Nintedanib for the treatment of malignant pleural mesothelioma by the United States Food and Drug Administration in December 2016. Currently Nintedanib, under the tradename Offev, is approved for the treatment of idiopathic pulmonary fibrosis.

In 2011, a clinical trial of patients who have idiopathic pulmonary fibrosis, a debilitating disease that affects the lungs, characterized by disease progression that includes lung deterioration and scarring. The disease is difficult to predict but the mean survival time from diagnosis is 2.5 to 3.5 years. This study in which 432 patients compared BIBF 1120 with a placebo and found those who took the drug Ofev had a decline in their rate of reduction of lung function, with fewer acute exacerbations and preserved the quality of life of the participants. Nintedanib was approved by the Federal Drug Administration in 2014 for the treatment of idiopathic pulmonary fibrosis.

The recommended dose is 150mg of Nintedanib is twice a day by mouth. It should be taken with food. It is not recommended for patients with liver disease, depending on the stage of the disease.

One of the most important thing to know is that OFEV can cause birth defects. Women should not become pregnant while taking OFEV,

Some of the more common side effects are elevation in liver function tests, diarrhea, nausea and vomiting. Decreased appetite was also reported. A small number of patients had thromboembolic events that have led to myocardial infarctions- heart attacks, strokes, and small number of gastrointestinal perforation.

Currently there are 4 Clinical Trials on www.clinicaltrials.gov listed for mesothelioma and Nintedanib. Three are recruiting and one is not yet recruiting. The LUME-Meso phase ll trial is a multicenter worldwide trial, with sites in the United States. The second trial is to be based in Europe, and is not yet recruiting. The third trial listed is based in the United States and is for treatment of recurrent mesothelioma with Nintedanib. The fourth trial is based in France for many solid tumor cancers, including mesothelioma and nintedanib.

We have reviewed the 2 clinical trials for Nintedanib and malignant pleural mesothelioma. One is being tested as a drug option for recurrence. The second is being given along with first line chemotherapy. The research is exciting and the results promising. Ask your mesothelioma doctor if your disease might benefit from these clinical trials.

MESOTHELIOMA CLINICAL TRIAL REVIEW – NINTEDANIB IN TREATING PATIENTS WITH MALIGNANT PLEURAL MESOTHELIOMA THAT IS RECURRENT

Posted on December 6, 2017 by Ellie and Lisa

We encourage participation in clinical trials for research leading to a cure for mesothelioma. It is known that nationally the statistics for participation in adult cancer trials is between 3-5% of adults who have a cancer diagnosis.

For mesothelioma patients and families who are interested in clinical trials, researching clinical trials and eligibility can be a time- consuming barrier to participation. The information about clinical trials is available on www.clinicaltrials.gov

CLINICAL TRIAL– NCT02568449

Official Title– A Phase II Trial of BIBF 1120 (Nintedanib) in Recurrent Malignant Pleural Mesothelioma

Listing on- www.clinicaltrials.gov

Sponsor- Barbara Ann Karmanos Cancer Institute Wayne State University 4100 John R Detroit, Michigan 48201

Collaborator: National Cancer Institute

Location: 4 total sites- 2 are recruiting 2 not yet recruiting-

University of Michigan Comprehensive Cancer Center Ann Arbor, Michigan, United States 48109 contact Gregory P. Kalemkerian 734 615 4762 kalemker@umich.edu- recruiting
Wayne State University/Karmanos Cancer Institute Detroit Michigan, United States 48201 contact Antoinette J. Wozniak 313 576 8752 wozniakt@karmanos.org -recruiting
University of California Davis Comprehensive Cancer Center Sacramento California, United States 95817 contact David R. Gandara 916 734 8452 david.gandara@ucdmc.ucdavis.edu- not yet recruiting
Memorial Sloan Kettering Cancer Center New York, New York, United States, 10065 contact Marjorie G. Zauderer MD zauderem@mskcc.org – not yet recruiting

Principal Investigator Antoinette J. Wozniak, Barbara Ann Karmanos Cancer Institute Wayne State University 4100 John R Detroit Michigan 48201

Contact– Listed above by site.

Number of Participants– 55 starting date October 2015- estimated completion date January 1, 2018

Purpose- A phase ll trial to study how well Nintedanib works in treating patients with malignant pleural mesothelioma that has come back. Nintedanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Eligibility Criteria- Adults over age 18 male or female

Inclusion and Exclusion Criteria:

Patients must have histologically confirmed diagnosis of unresectable malignant pleural mesothelioma
Patients must have a Ct scan within 28 days of beginning trial to measure disease- all disease must be assessed by the RECIST criteria.
Patients must have had prior systemically administered platinum-based chemotherapy; pleural space washing with cisplatin does not constitute systemic administration; no more than two prior systemic therapeutic regimens are allowed (including biologics, targeted and immunotherapies), and at least one regimen must have been platinum-based
No prior treatment with BIBF 1120 or any other vascular endothelial growth factor receptor (VEGFR) inhibitor
No known hypersensitivity to BIBF 1120, to its excipients or to contrast media
Patients may have received prior surgery (e.g., pleurectomy, pleurodesis) provided that at least 28 days have elapsed since surgery (thoracic or other major surgeries) and patients have recovered
No active brain metastases (e.g. stable for < 4 weeks, no adequate previous treatment with radiotherapy, symptomatic, requiring treatment with anti-convulsants; dexamethasone therapy will be allowed if administered as stable dose for at least one month before randomization); no leptomeningeal disease
No radiographic evidence of cavitary or necrotic tumors
No centrally located tumors with radiographic evidence (CT or magnetic resonance imaging [MRI]) of local invasion of major blood vessels
Institutions must offer patients the opportunity to submit tissue for future correlative studies
Patients may have received prior radiation therapy provided that at least 14 days have elapsed since the last treatment and patients have recovered from all associated toxicities at the time of registration
Patients must have a Zubrod performance status of 0-1
Absolute neutrophil count (ANC) >= 1,500/mcl
Platelet count >= 100,000/mcl
Serum bilirubin =< institutional upper limit of normal (IULN)
Liver tests- SGOT, AST, SGPT must be less than institution upper limit of normal
Renal tests- less than IULN obtained within 14 days
No proteinuria Common Terminology Criteria For Adverse Events (CTCAE) grade 2 or greater
No therapeutic anticoagulation (except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous device) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid < 325mg per day); no history of clinically significant hemorrhagic or thromboembolic event in the past 6 months
Patients must have no evidence of bleeding or coagulopathy; patients must have no pathologic condition other than mesothelioma that carries a high risk of bleeding
No major injuries within the past 10 days prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period
Patients must not have gastrointestinal tract disease resulting in an inability to take oral or enteral medication via a feeding tube or a requirement for intravenously (IV) alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease
No significant cardiovascular diseases ( i.e. uncontrolled hypertension, unstable angina, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure > NYHA [New York Heart Association Class] II, serious cardiac arrhythmia, pericardial effusion)
No active serious infections in particular if requiring systemic antibiotic or antimicrobial therapy
No active or chronic hepatitis C and/or B infection
Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method
No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years
No psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule
No active alcohol or drug abuse
All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

How the Research Study is Designed to Work-

PRIMARY OBJECTIVES:

To assess the 4-month progression-free survival (PFS) in patients with recurrent, unresectable malignant pleural mesothelioma (MAM) treated with Nintedanib.

SECONDARY OBJECTIVES:

To assess response rate (confirmed and unconfirmed, complete and partial responses) and disease control rate (response or stable disease) in the subset of patients with measurable disease by both RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 criteria and Modified RECIST criteria for pleural tumors.
To assess overall survival.

III. To evaluate the frequency and severity of toxicities associated with this treatment regimen.

To collect tissue samples for future correlative studies related to overall study objectives.

With any clinical trial, all participation is voluntary. Before enrollment a detailed consent form will be reviewed with the participant and signed. The participant can withdraw from a clinical trial at any point in time. Think about participating if able, the only way to progress to a cure for mesothelioma is through clinical trials.

Please do not hesitate to contact us with any questions.

MESOTHELIOMA CLINICAL TRIAL REVIEW – NINTEDANIB

Posted on December 6, 2017 by Ellie and Lisa

We encourage participation in clinical trials for research leading to a cure for mesothelioma. It is known nationally the statistic for participation in adult cancer trials is between 3-5% of adults who have a cancer diagnosis.

For mesothelioma patients and families who are interested in clinical trials, researching clinical trials and eligibility can be a time-consuming barrier to participation. The information about clinical trials is available on www.clinicaltrials.gov.

CLINICAL TRIAL- NCT01907100

Nintedanib (BIBF 1120) in Mesothelioma

Official Title- LUME-Meso: Double Blind Randomized, Multicentre, Phase 11/111 Study of Nintedanib in Combination with Pemetrexed /Cisplatin Followed by Continuing Nintedanib Monotherapy Versus Placebo in Combination with Pemextred/ Cisplatin Followed by Continuing Placebo Monotherapy for the Treatment of Patients with Unresectable Malignant Pleural Mesothelioma.

Listing on www.clinicaltrials.gov

Sponsor: Boehringer Ingelheim

Location: Multiple locations throughout the world. In the United States, there are 10 different locations.

University of Alabama at Birmingham Alabama 35249
University of California San Francisco California 94115
Rocky Mountain Cancer Centers, Colorado Springs, Colorado 80907
Comprehensive Cancer Centers of Nevada- Peak Office Henderson, Nevada 89052
University of Pittsburg Medical Center, Pittsburg Pennsylvania 15232
Greenville Health System, Greenville South Carolina 29615
University of Texas MD Anderson Cancer Center, Houston Texas 77030
Texas Oncology McAllen Texas 78503
Texas Oncology San Antonio Northeast San Antonio Texas 78217
Cancer Care Northwest Centers, PS Spokane Valley, Washington 99216

Principal Investigator: Giorgio V. Scagliotti MD, PhD, university of Torino Italy and Nicholas J. Vogelzang MD, Comprehensive Cancer Centers of Nevada- in the United States

Contact: Boehringer Ingelheim Call Center 1-800-243-0127 clintriage.rdg@boehringer-ingelheim.com

Number of Participants: Estimated – 537 – September 19, 2013 – October 30,2019

Purpose: This is a Phase ll/lll study to confirm that by adding nintedanib (BIBF 1120) in combination with first line therapy pemextred and cisplatin in one arm of the study- and a second arm having the first line therapy pemextred and cisplatin along with a placebo instead of Nintedanib.

The study will then primarily measure progression free survival measured by the time of randomization for the trial until disease progression, or death from any cause, whichever happens first. The time frame for this follow up is up to 3 years.

The secondary outcomes that will be measured are overall survival measured from the time of randomization to the time of death of any cause. Objective response according to the modified RECIST score. Disease control measured according to modified RECIST by disease control rate. The time frame on all these objectives is up to 3 years.

Screening: 18 years or older- male or female

Not have sarcomatoid sub type of malignant pleural mesothelioma

Eligibility Criteria: Histologically confirmed malignant pleural mesothelioma – Phase ll epithelioid or biphasic subtype only- Phase lll epithelioid subtype only

Life expectancy of at least 3 months- decision by the investigator
Eastern Cooperative Oncology Group (EGOG) score of 0 or1
Measurable disease according to modified RECIST (Response Evaluation in Solid Tumors) criteria

Exclusion Criteria: Previous systemic chemotherapy for malignant pleural mesothelioma

Prior treatment with Nintedanib or any other prior line of therapy

Phase ll patients with sarcomatoid subtype malignant pleural mesothelioma or Phase

lll patients with biphasic or sarcomatoid subtype malignant pleural mesothelioma

Patients with symptomatic neuropathy

Radiotherapy (except extremities) within 3 months prior to baseline imaging

Active brain metastases (e.g. stable for < 4 weeks)

Radiographic evidence of cavitary or necrotic tumors or local invasion of major blood

Vessels by malignant pleural mesothelioma

Significant cardiovascular diseases

Inadequate hematologic, renal, or hepatic function

How the Research Study is Designed to Work: By administering Nintedanib and a placebo to two different randomized groups of patients who have epithelial type malignant pleural mesothelioma, along with the first line chemotherapy agents, cisplatin and pemextred. The results will then be analyzed with attention to overall survival, time to progression of disease recurrence, and time toward death by any cause.

Sources: www.ClinicalTrials.gov

Raising Awareness About Rare Orphan Diseases Such as Mesothelioma

Posted on December 6, 2017 by Ellie and Lisa

Malignant mesothelioma is a rare disease. It is one of approximately 6,000 rare diseases that have been recognized. These diseases are often referred to as “orphan diseases” Rare diseases are those that affect fewer than 200,000 people in the United States, with a population of 330 million people. In other countries, the numbers are different –with numbers varying from 1 to 8 per 10,000 people. Having a rare disease, it follows that few medical professionals are experts as they see so few of these diseases in their practices. Some of the web sites that you can find information on are the National Organization of Rare Disorders (NORD) www.rarediseases.org. The United States government offers on its National Institute of Health web site, information on Genetics and Rare Disease Information Center www.rarediseases.info.nih.gov. GARD, created in 2002 by the National Human Genome Research Institute (NHGRI) and the Office of Rare Diseases Research (ORDR) to help people find information about rare diseases. Orphanet is another option for rare diseases and orphan drugs, the site is Europe focused and based.

It has been recognized that it is vital for patients and families to obtain, reliable up to date medical information for rare diseases. It is also important that they have the option of a supporting community, either on line or in person at conferences.

Some of the rare diseases we have all heard about such as mesothelioma, cystic fibrosis, Tourette’s Syndrome and Amyotrophic Lateral Sclerosis-“Lou Gehrig’s ” disease.

Rare diseases also have a day every year to increase awareness. It is held internationally on the last day of February. The theme for 2018 is research. February 28, 2018 is the next one planned.

Another issue when dealing with rare diseases is to get the pharmaceutical companies interested in research and development of drugs that will have a limited market. Research and development of drugs cost millions of dollars and many years to develop. According to the web site www.fda.gov/Drugs/ResourcesForYou/Consumers ; In 1983 Congress passed the Orphan Drug Act (ODA). The ODA created financial incentives for drug and biologics manufactures, including, tax credits for costs of clinical research, government grant funding, assistance for clinical research, and a seven-year period of exclusive marketing given the first sponsor of an orphan-designated product who obtains market approval from the Food and Drug Administration for the same indication. At the same time, federal programs at the FDA and the NIH began encouraging product development, as well as clinical research for products targeting rare diseases.

In 1983, the United States Food and Drug Administration established the Office of Orphan Product Development. Since this law was signed by President Reagan in 1983, more than 200 companies have brought almost 450 orphan drugs to market. Some of the drugs have been approved to treat other more common diseases and then are “repurposed” to treat rare diseases. For some rare diseases, the drug approval process is based on one well run clinical trial.

Please let us know if you have any questions.

MESOTHELIOMA CLINICAL TRIAL REVIEW – DANA-FARBER CANCER INSTITUTE (BOSTON, MASSACHUSETTS)

Posted on August 25, 2017 by Ellie and Lisa

For mesothelioma patients and families that are interested in clinical trials, researching clinical trials and eligibility can be a time-consuming barrier to participation. The information about clinical trials is available on www.clinicaltrials.gov.

Our goal is to feature one mesothelioma clinical trial monthly and break it down to understandable terms, to decipher the eligibility requirements, and to possibly encourage participation in these trials.

Listing-Clinical Trial.gov – NCT03075527

Title– A Phase 2 Study of Durvalumab in Combination with Tremelimumab in Malignant Pleural Mesothelioma

Official Title– A Phase 2 Study of Durvalumab in Combination with Tremelimumab in Malignant Pleural Mesothelioma

Sponsor- Dana-Farber Cancer Institute

Astra Zeneca- collaborator

Location- Dana-Farber Cancer Institute Boston Massachusetts

Principle Investigator– Mark M Awad MD Dana-Farber Cancer Institute

Contact- Mark M. Awad, MD, PhD 617 632 3468 mark_awad@dfci.harvard.edu

Patients will receive Durvalumab and tremelimumab both intravenous infusion once per day for every 28-day cycle. Participant s will receive tremelimumab for up to 4 cycles beginning with cycle 5 day 1. Patients will continue to receive durbalumab alon until clinical or radiological progression of disease

Tremelimumab blocks a receptor on immune cell that normally suppresses immune attack

Durvalumab is a drug that block a protein often produced by cancer cells or surrounding cells to suppress immune cells from attacking cancer cell

Number of Participants-40 Start Date April 10, 2017 Estimated Study Completion September 30, 2024

Purpose– The study is studying two immunotherapies as possible treatment for malignant pleural mesothelioma. Those drugs are Durvalumab and Tremelimumab. This is a phase 11 clinical trial

Eligibility Criteria– 18 Years and older

Inclusion Criteria:

Written informed consent prior to any study-specific procedures not considered part of routine medical care
Histologically or cytological confirmed unresectable or medically inoperable malignant pleural mesothelioma
Disease progression after treatment with at least one line of chemotherapy that include a first line platinum agent in combination with an anti-folate
Participants must have measurable disease according to modified RECIST for pleural malignant mesothelioma. (Bone metastasis are not considered measurable) Prior radiation to the only site of measurable disease will make the participant ineligible unless the lesion has been demonstrated to grow after the completion of radiation therapy
Participants must be willing to undergo a biopsy at the start of this study and an on –treatment biopsy if safe and feasible
Participants must be at least 28 days from any major surgery
ECOG performance status of 0 to 1
Patients must t have adequate hematologic renal, organ and marrow function
Must be 18 years and older
Female and Males who are of childbearing ages must consent to one form of contraception from the time of screening and must continue until 180 days after last dose of investigational product.
Patient is willing to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examination including follow up

Exclusion Criteria–

previous treatment with an immune checkpoint inhibitor, CTLA-4, PD-1, or PD-L1, including prior treatment with either durvalumab or tremelimumab
Known central nervous system metastasis. Patients with known brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease may be enrolled if they have been treated, and are no longer taking corticosteroids and have been stable in imaging for at least 3 weeks
Patient receiving corticosteroids doses greater than 10 mg per day for more than 14 days
Patients receiving other systemic immunosuppressive drugs for more than 14 days
Patients with a history of interstitial lung disease or pneumonitis that has required steroid administration
Active or prior documented autoimmune disease within the past 2 years including but not limited to systemic lupus erythematosus, sarcoidosis syndrome, or Wegener’s granulomatosis Patients with Grave’s disease or psoriasis not requiring systemic treatment within the past 2 years not excluded
Inflammatory bowel disease or any other serious gastrointestinal condition associated with diarrhea
History of primary immunodeficiency
History of allogenic organ transplant
History of hypersensitivity to tremelimumab, durvalumab or any excipient
Know history of tuberculosis
Receipt of live attenuated vaccination within 3o days prior to study entry or within 30 days of receiving durvalumab or trememlimumab
Patient with history of secondary primary malignancy. If patient had curative malignancies with no recurrence within 5 years prior to study. Resected basal and squamous cell carcinomas of the skin, and completely resected carcinoma in situ of any type.
Patient who have had chemotherapy, biologic therapy or investigational therapy with 21 days including bevizumab or radiotherapy with 7 days prior to entering the study or those who have not recovered from adverse events due to the administration of these agents
If you have received any previous immunotherapy agent with adverse event at least or greater than grade 3
You cannot receive any other investigational agents
Active infections, gastritis symptomatic heart failure, hypertension, ( sbp greater than 160/100with medications)
Unstable angina
Cardiac arrhythmia
Active bleeding diatheses
Active peptic ulcer disease
Psychiatric illness or social situations that would limit compliance with study
Mean QT interval corrected for heart rate greater than 470 ms calculated from 3 electrocardiograms using Frederica’s correction
Known history of HIV
Acute or chronic hepatitis B or hepatitis C
Pregnant women
If involved with planning and/or conduct of Astra Zeneca staff and or staff at the study site
If patient has had a pneumonectomy
How the research Study is Designed to Work

Phase 11 clinical trial tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. The drugs durvalumab or tremelimumab are being studied to see how the drugs help as compared to the usual treatment for malignant mesothelioma.

Durvalumab is a drug that blocks a protein often produced by cancer cells or surrounding cells to suppress immune cells from attacking cancer cells.

Tremelimumab blocks a receptor on immune cells that normally suppress immune attack.

Both of these drugs have been used for treatment of malignant mesothelioma, but the combination has not been tried in treatment in mesothelioma. They have been used successfully together in melanoma.

Sources:

www.ClinicalTrials.gov

With any clinical trial, all participation is voluntary. Before enrollment a detailed consent form will be reviewed with the participant and signed. The participant can withdraw from a clinical trial at any point in time. Think about participating is able, the only way to progress to a cure for mesothelioma is through clinical trials.

Please do not hesitate to contact us with any questions.

MESOTHELIOMA CLINICAL TRIAL REVIEW – INTRAPLEURAL CRYOTHERAPY FOR MALIGNANT PLEURAL MESOTHELIOMA

Posted on June 6, 2017 by Ellie and Lisa

Clinical Trial – NCT 02464904

Official Title: Intrapleural Cryotherapy for Malignant Pleural Mesothelioma

Listing on: www.clinicaltrials.gov

Sponsor: Mayo Clinic

Location: Mayo Clinic Rochester, Minnesota

Principal Investigator: Shanda H Blackmon, MD, MPH Mayo Clinic

Contact: Karlyn Pierson, RN, MAN 507-538-1960 pierson.karlyn@mayo.edu

Bettie Lechtenberg, MBA 507-266-4819 lechtenberg.bettie@mayo.edu

Purpose: To see if neoadjuvant cryotherapy be safely performed in patients with malignant pleural mesothelioma and will it trigger a systemic and or local pro-inflammatory response in the induction of anti-tumor immunity.

Primary outcome Measure Number of patients with adverse events. Patients will be monitored for adverse events that may have resulted from a pleuroscopy procedure.

Estimated Enrollment 15

Study Start time July 2015

Estimated study completion date June 2017

Estimated Primary completion date June 2017

The study is still open and actively recruiting

Interventions: Patient will have their blood drawn prior to pleuroscopy for staging purposes. The biopsy will consist of pleural fluid and pleural biopsies that will have consist of 4-8 biopsies. During the procedure, there will be 2-3 applications of cryospray applied to the disease. (Usually the chest wall area). The minimum area is a 2×2 cm area which will continue for 15-20 seconds then thaw for 60 seconds followed by 1 to 2 times of cryotherapy before moving on to the next area. The freezing procedure will be video recorded and freezing locations and times will be recorded. Approximately 14 days following the staging pleuroscopy patients will undergo surgical treatment as per standard of care. Blood and pleural fluid and tissue collection will be performed as well.

Description: Patient that have been diagnosed or thought to have malignant pleural mesothelioma. Prior to surgery for treatment a pleuroscopy or video camera exam of the pleura will be conducted to establish diagnosis or extent of the disease. The purpose of this research is to gather information on the safety and effectiveness for cryotherapy in patients with malignant pleural mesothelioma.

Eligibility: Must be 18 years old male or female

Inclusion Criteria

Patients provide informed consent
Patients 18 years of age
Patients competent for making informed decisions
Patient will undergo pleuroscopy as part of their standard care for pre-operative clinical staging of malignant pleural mesothelioma.
Pregnancy test is required to be negative
Patient is mentally capable of understanding process of study

Exclusion Criteria

Patient that have an INR 1.5 or greater
If patient is on anticoagulants such as heparin, warfarin, and other types of anticoagulation have not been held for the standard time
Vital signs will be stable heart rate greater than 120 unless deemed stable with these values by the surgical or interventional pulmonary attending physician. Also, systolic blood pressure will also not be less than 90 mmHG unless deemed stable
Hypoxia with oxygen saturation less than 88% or a PA02 less than 60 measured from arterial blood gas.
Participating in another study involving the investigational drugs or investigational medical devices
If there is limited access to the pleural space or absence when performing medical pleuroscopy
Inability to read and understand the necessary study documents

Sources:

www.ClinicalTrials.gov

Please do not hesitate to contact us with any questions.

Definition of Terms

Cryotherapy- is the therapeutic use of cold, is a technique that uses extremely cold liquid or an instrument to freeze and destroy abnormal cells. Used on common benign conditions such as warts and certain skin cancers.

Pleuroscopy- is the examination of the pleural cavity with an endoscope, through an incision on the thorax (chest).

Cryospray- the use of liquid nitrogen spray in cryosurgery

Cryosurgery- an operation using freezing temperature as an agent or an independent agent in an instrument to destroy tissue. It is the destruction of tissue using extreme cold: silver nitrate, and carbon dioxide are commonly used.

Source: www.medical-dictionary

MESOTHELIOMA CLINICAL TRIAL REVIEW – NYU IMMUNOTHERAPY

Posted on May 16, 2017 by Ellie and Lisa

For mesothelioma patients and families who are interested in clinical trials, researching clinical trials and eligibility can be a time-consuming barrier to participation. The information about clinical trials is available on www.clinicaltrials.gov

Our goal is to feature one mesothelioma clinical trial monthly and break down to understandable terms, to decipher the eligibility requirements, and to possibly encourage participation in these trials.

CLINICAL TRIAL- NCT02718911

A Study of LY-33022855 in Combination With Durvalumab or Tremelimumab in Participants With Advanced Solid Tumors

Official Title- A Phase 1a/1b Trial Investigating the CSF-1R Inhibitor LY3022855 in Combination With Durvalumab (MED14736) or Tremelimumab in Patients With Advanced Solid Tumors

Listing on www.clinicaltrials.gov

Sponsor: Eli Lilly and Company – Collaborator Astra Zeneca

Location: Multiple locations throughout the world

Principal Investigator: Leena Gandhi M.D.at NYU – Study Director 1-877-285-4559 at Eli Lilly

Contact: NYU- 212 731 6199

Number of Participants: Estimated 178

Purpose: -The focus of this study is to evaluate the safety of the colony-stimulating factor 1 receptor (CSF-1R) inhibitor LY3022855 in combination with durvalumab or tremelimmab in patients with advanced solid tumors

Screening: – Must be willing to undergo pretreatment and on-treatment core needle or excisional tumor biopsies

Lab test that include:

absolute neutrophil count> 1.5 x 10.9/Liters
Platelet count. 100,000/ cubic millimeters
Hemoglobin >9 gams per decliter
Serum creatine, 1.5 x institutional upper limit of normal (ULN)
Total billrubin <1.5 x institutional ULN
- Asparate aminotransferase (AST) and alanine aminotransferase (ALT), <2.5x institutional ULN or <5 x institutional ULN for participans with liver metastasis
- International normalized ratio (INR) or prothrombin time (PT) INR, 1.5 x institutional ULN or PT <% seconds above institutional ULN

Eligibility Criteria: Must have histological or cytological evidence of a diagnosis of cancer that is not amendable to curative therapy

Part B must have a type of malignancy that is being studied

Part A (all cohorts): Have the presence of measurable and/ or no measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST)

Part B (all cohorts) Have the presence of measurable disease as defined by the RECIST

PTT or activated partial thromboplastin time (aPTT) < 5 seconda above institutional ULN

Thyroid stimulating hormone (TSH) or free thyroxine (T4) within the normal limits

Have a performance status 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale

Exclusion Criteria: Are currently receiving or have used immunosuppressive medications within 28 days

Have symptomatic central nervous system (CNS) malignancy or metastasis

Have had any prior Grade>3 immune-related adverse event while receiving any previous immunotherapy agent

Have experienced a Grade>3 AE or a neurologic or ocular AE while receiving prior immunotherapy

How the Research Study Is Designed to Work: Trying to find the maximum dose tolerated by patients of drug LY3022855 when given in combination with Durvalumab- one group – another group LY3022855 and Tremelimumab. One group given escalating doses, the endpoint would be the maximum tolerated dose and measure the response through progression of disease, stable disease, complete response or death.

Sources: www.ClinicalTrials.gov

Please do not hesitate to reach out with any questions.

Definition of Terms

Phase 1a/1b- initial phase of testing of an investigational drug in humans. Used to determine the side effects of the drug and how it works. Phase 1 is sometimes sub-divided into phases 1a and 1b with different doses being measured. New drug being combined with standard of care to find out what dose is best tolerated

Colony- stimulating factor 1 receptor (CSF-1R)- protein encoded by this gene is the receptor for colony stimulating factor 1- cytokine which controls the production, differentiation and function of macrophages. macrophages are important cells of the immune system that are formed in response to an infection. They are large specialized cells that recognize engulf and destroy target cells.

LY3022855- Human monoclonal antibody designed to target CSF1R, preventing ligands CSF1. Being investigated in phase 1 clinical trials, including a collaboration clinical trial with another immuno-oncology agent.

Durvalumab- another name is Imfinzi-ANTI pd-L1 antibody- blocks PD-l1 binding to PD-1 and CD 80- monoclonal antibody being used in treatment of some cancers

Tremelimumab- human immunoglobulin (Ig) G2 monoclonal antibody directed against the human T-cell receptor protein cytotoxic T-lymphocyte- associated protein 4 (CTLA4 with potential immune checkpoint inhibitory and antineoplastic activities.

Solid Tumor- is an abnormal mass of tissue that usually does not contain cysts or liquid area. Solid tumors may be benign (not cancer), or malignant (cancer). Different types of solid tumors are named for the type of cells that form them. Examples of solid tumors are sarcomas, carcinomas, and lymphomas. Leukemias (cancers of the blood) generally do not form solid tumors.

Source www.cancer.gov

MESOTHELIOMA CLINICAL TRIAL REVIEW- GENETICALLY MODIFIED T CELLS IN TREATING PATIENTS WITH STAGE III-IV NON- SMALL CELL LUNG CANCER OR MESOTHELIOMA

Posted on February 17, 2017 by Ellie and Lisa

Listing- ClinicalTrials.gov- NCT02408016

Official Title- Phase I/II Study in WT1-Expressing Non- Small Cell Lung Cancer and Mesothelioma, Comparing Cellular Adoptive Immunotherapy With Polyclonal Autologous Central Memory to Naïve CD8+ T Cells That Have Been Transduced to Express a WT1- Specific T-Cell Receptor

Sponsor- Fred Hutchinson Cancer Research Center

Location- Fred Hutch/University of Washington Cancer Consortium Seattle Washington 98109

Principal Investigator-Sylvia M. Lee- 206 288 2274 smlee@fredhutch.org

Contact- Sylvia M. Lee 206 288 2274 smlee@fredhutch.org

Purpose- This phase 1/11 trial studies the side effects and best dose of genetically modified T cells in treating patients with stage 111-IV non-small cell lung cancer (NSCLC) or mesothelioma. Many types of cancer cells, including NSCLC and mesothelioma, but not most normal cells, have a protein called Wilms tumor (WT)1 on their surfaces. This study takes a type of immune cell from patients, called T cells, and modifies their genes in the laboratory so that they are programmed to find cells with WT1 and kill them. The T cells are then given back to the patient. Cyclophosphamide and aldesleukin may also stimulate the immune system to attack cancer cells. Giving cyclophosphamide and aldesleukin with laboratory – treated T cells may help the body build an immune response to kill tumor cells.

Screening– Documentation of NSCLC or mesothelioma by histopathological sample

Patient must be able to give informed consent
Patient must be able to provide blood and tumor samples and undergo the procedures
Required for this protocol

Eligibility Criteria—Inclusion therapy- Three arms of study- For Arm 1

Patient must express human leukocyte antigen (HLA)- A*0201
Evidence of WT1 tumor expression
Patients must have received at least one line of therapy for NSCLC or mesothelioma or previously documented to have declined therapy

NSCLC patients with a mutation in epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) must have demonstrated progression or intolerance to at least one of the corresponding targeted therapies (for example erlotinib or crizotinib)

Bi-dimensionally measurable disease by palpation, clinical exam, or radiological imaging (X-ray, computed tomography (CT) scan, positron emission tomography (PET) scan, magnetic resonance imaging (MRI) or ultrasound)

Ninety days must have passed since the last doses of radiation or chemoradiation treatment involving lung tissue or thorax prior to T cell infusion

Patients treated with prior immunotherapy including and not limited to vaccines, cytokines. T cell stimulating agents, cytokines, T cell stimulating agents, cytoxic T lymphocyte antigen 4 (CTLA4) inhibitors and programmed death (PD)-1 check point inhibitors are allowed on therapy provided they did not have any severe grade 4 toxicities due to prior therapy and any toxicities due to prior therapy should have resolved. If resolvable to less than or equal to grade one

ELIGIBILITY FOR TREATMENT ON ARM 2

Patients must express HLA-A*0201
Evidence of WT 1 tumor expression
Ninety days must have passed since the last definitive doses of radiation or chemoradiation treatment prior to T cell infusion

Exclusion Criteria– EXCLUSION FOR ENROLLMENT / SCREENING (ARMS 1 AND 2)

. Performance status by Eastern Cooperative Oncology Group (ECOG) performance status >=2
Active autoimmune disease in which possible progression during treatment would be considered unacceptable by the investigators
Any condition or organ toxicity deemed by the (PI) or the attending physician to place the patient at unacceptable risk for the treatment of the protocol
Men or women of reproductive ability who are willing to use effective contraception or abstinence; women of childbearing potential must have a negative urine test within two weeks prior to first infusion.
Pregnant women and nursing mothers will be eligible for screening only to test HLA type by saliva or buccal swab and WT1 expression from previously collected tissue sample
Clinically significant and ongoing immune suppression including, but not limited to, systemic immunosuppressive agents such as cyclosporine or corticosteroids

EXCLUSION FOR TREATMENT (ARMS 1 and 2)

Exclusions for the leukapheresis procedure (can be performed later as symptoms resolve)
Infection with or without antibiotic treatment
Recent hepatitis exposure
Pregnancy or nursing
HIV or human T-lymphotropic virus (HTLV) infection
Positive result on standard test for Syphilis
Unable to generate antigen-specific WT1-specific CD8+T cells for infusions; however, the patient will have the option to receive WT1-specific T- cells if a lower than planned number of cells is available
Documented infections or known oral temperatures >38.2 degrees Celsius © fewer than 72 hours prior to receiving study treatment or systemic infection requiring chronic maintenance; the start of treatment may be delayed
Systemic steroids should be stopped 2 weeks before the start of treatment; topical and inhaled steroids are allowed
Untreated central nervous system (CNS) metastasis that are > 1cm or symptomatic are not allowed; (patients with CNS metastases >1 cm or symptomatic that have been treated and demonstrated to be radiologically and clinically stable for at least 4 weeks are allowed
WBC- White blood cells < 2,000/ul
Hemoglobin (Hb) <8 g/dl
ANC- Absolute neutrophil count < 1000/ul
Platelets < 50,000/ul
Creatinine >1.5x the upper limit of normal
Aspartate aminotransferase/ alanine aminotransferase (AST/ALT) > 5x upper limits of normal (ULN)
Bilirubin >3 x ULN that cannot be attributed to NSCLC metastasis
HIV or HTLV infection
New York Heart Association functional class lll-lV heart failure, symptomatic pericardial effusion, stable or unstable angina, symptoms of coronary artery disease (CAD), congestive heart failure, clinically significant hypotension or history of an ejection fraction of =<30%

Clinically significant pulmonary dysfunction, as determined by medical history and physical exam, patients identified will undergo pulmonary functions testing and those with forced expiratory volume in the 1 second (FEV1) < 2.0 L or diffusion capacity of the lungs for carbon monoxide (DLCO) (corrected for Hb) < 50% will be excluded

How the Research Study is Designed to Work- Patients are assigned to 1 of 3 treatment arms. This is a phase 1, dose escalation study of autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes followed by a phase 11 study. Once the cells have been reconstucted the cells are given back to the patient with intent that cells will attack to tumor cells.

Sources: www.ClinicalTrials.gov

Please do not hesitate to contact us with any questions.

MESOTHELIOMA SPECIALIST SPOTLIGHT: DR. FARHOOD FARJAH

Posted on February 17, 2017 by Ellie and Lisa

Dr. Farhood Farjah is a thoracic surgeon and researcher. He holds an appointment as an Assistant Professor of Surgery at the University of Washington. Dr. Farhood Farjah obtained his medical degree at Oregon Health and Science University and trained at the University of Washington in general surgery. He did his residency at University at Washington Medical Center and his fellowship at Memorial Sloan-Kettering Cancer Center in New York in cardiothoracic surgery. Dr. Farjah’s postdoctoral research fellowship was funded by the National Institute of Health and National Cancer Institute. Dr. Farjah also has a master’s degree in epidemiology and is the Associate Medical Director of the Surgical Outcomes Research Center. (SORCE).

As a young man, he had always been interested in helping and working directly with people, service and science. Dr Farjah is committed to understanding patients’ goals and helping them achieve them. He plans to use his training, experience and network of colleagues to help patients achieve their goals.

He is involved with research that studies how doctors deliver care to lung cancer and mesothelioma patients in the United States. His goal is that all patients have the best possible outcome. Another of his goals during his research is to increase the quality and value of thoracic oncology patients experiences.

Dr. Farjah has a special interest in occupational related illnesses, including mesothelioma and lung cancer. In addition to treating mesothelioma and lung cancer patients, Dr. Farjah has lectured on the treatment of mesothelioma, including a recent continuing medical education course on “Multi-Modality Treatment of Pleural Mesothelioma.” Dr. Farjah has also taught at the American College of Surgeons. The mesothelioma community is fortunate to have Dr. Farjah to help in the fight against mesothelioma and to help patients, especially those in the Pacific Northwest.

MESOTHELIOMA CENTER REVIEW – UNIVERSITY OF WASHINGTON

Posted on February 17, 2017 by Ellie and Lisa

We recommend that when you or your family member is diagnosed with mesothelioma that you be evaluated at an academic, multidisciplinary, mesothelioma center. In order to help you become familiar with what a center can offer, we feature one center per month.

University of Washington Medical Center

1959 NE Pacific Street

Seattle Washington 98195

Phone: 206-598-3300

Mission – “To improve the health of the public.”

University of Washington has been recognized as one of the top five cancer centers in the United States. University of Washington Medical Center, in collaboration with the Seattle Cancer Care Alliance and Fred Hutchinson Cancer Research Center, is the only National Comprehensive Cancer Network in the Pacific Northwest.

History – The University of Washington Medical Center was founded on May 4, 1959. The University of Washington lung cancer team is composed of leading healthcare professionals with extensive clinical expertise. The team offers a multidisciplinary approach to your individual cancer. Based on the type and location of your cancer, the genetics, life circumstances, and other unique factors, the treatment plan is developed.

Depending on your diagnosis, you will receive care at University of Washington Medical Center, Northwest Hospital & Medical Center or the Seattle Cancer Care Alliance. The Seattle Cancer Care Alliance is a cooperative alliance of UW Medicine, Fred Hutchinson Cancer Research Center and Seattle Children’s Hospital.

Diagnosis of lung cancer and mesothelioma are seen at the Seattle Cancer Care Alliance, 825 Eastlake Ave. E PO Box 19023 Seattle, WA 98109-1023- Patient intake office 206 288 7222

Director – Seattle Cancer Care Alliance

Dr. Michael S. Mulligan MD- Director of Advanced Lung Disease Surgery Program He performs a range of lung cancer resections..

Team – Keith D. Eaton PHD Medical Oncologist Dr. Bernardo H.L. Goulart, MD MS Medical Oncologist Renato G. Martins, MD MPH medical director for thoracic/head and neck oncology.

Dr. Marcus Neubauer MD medical oncology , Dr. Patel is a radiation oncologist who specializes in the treatment of thoracic cancer including lung, thymic and tracheal tumorsDr. Christin Rodriguez Md medical oncologist

Dr Farhood Farjah M.D. – thoracic surgeon at University of Washington- trained at Memorial Sloan –Kettering Cancer Center in cardiothoracic surgery

Affiliations Thoracic Surgery Clinic at University of Washington Medical Center and Seattle Cancer Care Alliance at South Lake Union

Stats – University of Washington Medicine is one of the top academic research institutes in National Institute of Health funding.

UW is recognized as a national leader in biomedical research

Resources – The Seattle Cancer Care Alliance Hospitality House offers a variety of apartment style units within blocks of the SCCA outpatient clinic. Reservations: 206-204-3700 or email sccahouse@seattlecca.org

The Seattle Cancer Alliance Hospitality House offers a shuttle bus to local grocery store twice a day. The shuttle also offer rides to and from hospital

Seattle Cancer Care Alliance have computer workstations, internet connections, fax machines, copier and printer, free notary and wig fitting

They also offer a lending library which may help with ones cancer journey.

Seattle Cancer Center also offers support for children, teens and caregivers.

Contact – Schedule an appointment 1-855-557-0555

People diagnosed with Mesothelioma are seen in the general oncology clinic on 4^th floor at Seattle Cancer Care Alliance Clinic Building. Treatments for this disease may occur in this building. Surgical procedures however take place at University of Washington Medical Center where follow up appointments maybe necessary.

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