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 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.

CLINICAL TRIAL- NCT02592551

Med14736 or Med14736 + Tremelimumab in Surgically Resectable Malignant Pleural Mesothelioma

Official Title- Window of Opportunity Phase 11 Study of MED14736 or MED14736 + Tremelimumab in Surgically Resectable Malignant Pleural Mesothelioma

Listing on www.clinicaltrials.gov

Sponsor:   Baylor College of Medicine

Location:   Baylor St. Lukes Houston Texas

Principal Investigator:   Bryan Burt MD. Baylor College of Medicine

Contact:     Michelle G Almarez BBA 713 798 3680 Michelle.Almarez@bcm.edu

Or:             Bryan Burt MD 713 798 8266   Bryan.Burt@bcm.edu

Purpose: The objective of this study is to determine whether MEDl4736 or combination therapy with MEDl4736 + tremelimumab are associated with favorable alterations of the intratumoral immunologic environment in subjects undergoing surgery for Malignant Pleural Mesothelioma.

Screening:

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Adequate normal organ and marrow function as defined below: Hemoglobin > 9.0 absolute neutrophil count (ANC) greater than 1.5 x109/lL, platelet count greater than 100,000, serum bilirubin less than 1.5x institutional limits, creatinine clearance less than 2.0 or calculated creatinine clearance greater than 50 ml/min as determined by the Cockcroft-Gault equation.

Any malignant pleural mesothelioma epithelial, mixed or sarcamatoid

N2 Nodal disease if no progression after 2 cycles of chemotherapy

NO or N1 nodal disease as present on perioperative chest ct or pet ct

Eligibility Criteria:

• Patients must be 18 years of age
• Eastern Cooperative performance status of 0 or 1 Females must be non-reproductive potential (post-menopausal, hysterectomy, bilateral tubular ligation, oophorectomy or have negative serum pregnancy test.
• Patient is willing to adhere to protocol
• Have pleural mesothelioma constricted to one lung. Patient is staged at NO or N1 determined by chest ct or pet ct
• Have N2 disease no progression after 2 cycles of chemotherapy. Patient will be considered if N1 or N2 develops during chemotherapy.

Exclusion Criteria:

• Patient involved in another clinical trial within 3 months
• Any treatment with PD1 or PDL-1 inhibitor including MEDI4736
• N3 nodal disease
• Uncontrolled seizures
• Previous diagnosis of tuberculosis
• History of transplant
• Pregnant or breastfeeding
• Uncontrolled brain metastasis requiring treatment
• Known history of immunodeficiency
• Hypersensitivity to MEDI4736 or tremelimumab
• Uncontrolled illness including heart failure, angina, peptic ulcer disease, gastritis, active bleeding, chronic hepatitis b or c, HIV, psychiatric illness
• History of leptomenigeal carcinomatosis
• Had drugs with laxative properties and herbal or natural remedies for constipation within 90 days of receiving MEDI 4736 or MEDI and tremelimumab
• Had vaccine within 30 days of receiving tremelimumab or within 6 months of receiving MEDI4736 or MEDI and Trememlimumab
• Had sunitinib within 3 months of receiving tremelimumab
• If you have had active or prior documented bowel disease
• Active or prior documented autoimmune disease within the last 2 years
• Any adverse event while receiving immunotherapy
• Any toxicity while receiving cancer treatment
• Any immunosuppressive drugs 28 days prior to to the clinical trial drugs and 90 days’ post infusion of treatment drug
• Mean QT interval corrected for heart rate (QTc) > 470 ms calculated from 3 electrocardiograms (ECG’s) using Bazett’s Correction
• Had any chemotherapy ,immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization ,monoclonal antibodies, other investigational drugs 30 days prior to first dose of study drug

How the Research Study is designed to work

Patients who have malignant pleural mesothelioma undergo a cervical mediastinal lymph node biopsy and also simultaneously undergo a biopsy of the pleura by thorcoscopy. The biopsy tissue must be 2 grams. In addition to these biopsies patient will also have blood drawn for this study. Approximately 1-2 weeks’ patients will be given MEDI-4736(15mg/kg once intravenously) or MEDI-4736(1500 mg once intravenous) also will receive tremelimumab (75 mg once intravenously) or a control group. There will be 2 treated arms and one controlled arm (untreated). Approximately two or three weeks’ patient will undergo surgical resection surgery either extra pleural pneumonectomy, or pleurectomy, and decortication. During this surgery the tumor will be removed and studied. At the initiation of surgery blood will be taken. Also the sixth rib will be removed at time of surgery. The surgery will include the standard treatment which includes intraoperative chemotherapy .

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 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.

Some of the terms used in the description of clinical trials can be confusing. For this clinical trial a definition of some of the terms are below.

Durvalumab- code name MEDI4736 or MEDI-4736- is a Fc optimized monoclonal antibody directed against cell death-1 ligand, with potential immune checkpoint inhibitory and anti-neoplastic activity. When given intravenously it binds to PD-L1- it then will reverse T-cell inactivation and activate the immune system to exert a cytotoxic T lymphocyte (CTL) response against PD-L1 expressing tumor cells.

Tremelimumab- code name CP-675 CP-675,206 – A human immunoglobulin (Ig) G2 monoclonal antibody directed against the human T-cell receptor protein cytotoxic T-lymphocyte associated protein 4 (CTLA4), with potential immune check point inhibitory and antineoplastic activities.

Source: National Cancer Institute Drug Dictionary