Phase II MEDI4736 in Combination With Chemotherapy for First-Line Treatment of Unresectable Mesothelioma
- Registration Number
- NCT02899195
- Lead Sponsor
- PrECOG, LLC.
- Brief Summary
Patients with pleural mesothelioma that can not be surgically removed will receive durvalumab, in combination with standard chemotherapy of pemetrexed and cisplatin as first-line treatment.
Durvalumab is a type of drug called a monoclonal antibody (a type of protein). Laboratory tests show that it works by allowing the immune system to detect your cancer and reactivates the immune response. This may help to slow down the growth of cancer or may cause cancer cells to die.
The purpose of this study is to see whether adding durvalumab to standard chemotherapy will improve overall survival (OS).
- Detailed Description
Mesothelioma is a malignant tumor of the mesothelial surfaces primarily arising in the thoracic pleura and is estimated to cause 43,000 deaths worldwide each year with over 3300 cases occurring annually in the United States. Approximately 80% of cases of mesothelioma are due to inflammation induced by prior asbestos exposure with a lead time from exposure to development of cancer of 20-30 years.
This is a single arm, open label phase II study of the anti-PD-L1 antibody, durvalumab, in combination with standard chemotherapy. Pemetrexed and cisplatin will be given for up to six 3-week cycles with the addition of concurrent durvalumab dosed every 3 weeks. The first 6 patients who are enrolled and commence treatment will be monitored for safety of the combination. Use of carboplatin in place of cisplatin will be permitted for patients who are ineligible for cisplatin due to impaired renal function at screening, however these patients must otherwise fulfill the eligibility criteria for the study. For patients that receive cisplatin, carboplatin may also be substituted after Cycle 1 for cisplatin related toxicity (e.g., grade 3 ototoxicity, grade 3 nausea) at the investigator's discretion. After completion of Cycle 6 of concurrent therapy, patients with stable or responding disease per modified RECIST for malignant mesothelioma will continue on single agent durvalumab every 3 weeks until progression. Maximum duration of durvalumab treatment is 12 months starting from Cycle 1 of concurrent treatment (inclusive of any treatment delays or missed treatments).
Tumor assessments will be performed approximately every 6 weeks during concurrent therapy and every 9 weeks during the maintenance phase.
Mandatory pre-treatment tumor tissue sample (i.e., obtained during a previous procedure or biopsy) and blood samples (prior to Cycle 1, Cycle 2 and Cycle 5) for research will also be required.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 55
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Durvalumab Durvalumab Pemetrexed/cisplatin will be given for up to six 3-week cycles with the addition of concurrent durvalumab every 3 weeks. The first 6 patients who are enrolled and commence treatment will be monitored for safety of the combination. Use of carboplatin in place of cisplatin will be permitted for patients who are ineligible for cisplatin due to impaired renal function at screening. For patients that receive cisplatin, carboplatin may also be substituted after Cycle 1 for cisplatin related toxicity (e.g., grade 3 ototoxicity, grade 3 nausea) at the investigator's discretion. After completion of Cycle 6 of concurrent therapy, patients with stable or responding disease per modified RECIST for malignant mesothelioma will continue on single agent durvalumab every 3 weeks until progression. Maximum duration of durvalumab treatment is 12 months starting from Cycle 1 of concurrent treatment (inclusive of any treatment delays or missed treatments).
- Primary Outcome Measures
Name Time Method Overall Survival (OS) From randomization until death, up to 32 months Overall survival (OS) is defined as the time from randomization to death from any cause. Patients that have not had an event reported at analysis will be censored at their date of last follow-up.
- Secondary Outcome Measures
Name Time Method Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03 Up to 15 months from start of treatment Number of participants with abnormal laboratory values and/or adverse events related to treatment.
Progression-Free Survival (PFS) From randomization until disease progression or death from any cause, up to 32 months Progression-free survival (PFS) is defined as the time from randomization to documented disease progression or death from any cause, whichever occurs first. Patients who have not experienced an event of interest by the time of analysis will be censored at the date they are last known to be alive and progression-free.
Time to Progression (TTP) on Durvalumab From time concurrent treatment started until progression, up to 32 months TTP measured from the time concurrent treatment with chemotherapy/durvalumab begins until radiologic or clinical progression is noted.
Objective Response Rate (ORR) From randomization until end of treatment, up to 15 months ORR assessed in accordance with RECIST 1.1 (modified for malignant mesothelioma).
Trial Locations
- Locations (20)
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
University of Miami Hospital
🇺🇸Miami, Florida, United States
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
Hillman Cancer Center Research Pavilion
🇺🇸Pittsburgh, Pennsylvania, United States
University of Washington Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Metro Minnesota Community Oncology Research Consortium
🇺🇸Saint Louis Park, Minnesota, United States
University of Colorado, Anschutz Cancer Pavilion
🇺🇸Aurora, Colorado, United States
St. Joseph Mercy Hospital
🇺🇸Ann Arbor, Michigan, United States
University San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
Ronald Reagan UCLA Medical Center
🇺🇸Los Angeles, California, United States
Stanford Cancer Institute
🇺🇸Stanford, California, United States
NorthShore University HealthSystem
🇺🇸Evanston, Illinois, United States
New York University Laura and Isaac Perlmutter Cancer Center
🇺🇸New York, New York, United States
Washington University in St Louis
🇺🇸Saint Louis, Missouri, United States
UTSW Medical Center
🇺🇸Dallas, Texas, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Aurora Cancer Center
🇺🇸Wauwatosa, Wisconsin, United States