Phase II MEDI4736 in Combination With Chemotherapy for First-Line Treatment of Unresectable Mesothelioma (PrE0505)
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|ClinicalTrials.gov Identifier: NCT02899195|
Recruitment Status : Active, not recruiting
First Posted : September 14, 2016
Results First Posted : April 6, 2021
Last Update Posted : November 12, 2021
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).
|Condition or disease||Intervention/treatment||Phase|
|Mesothelioma Pleural Mesothelioma||Drug: Durvalumab||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||55 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Concurrent therapy with Durvalumab, Pemetrexed and Cisplatin (or Carboplatin) for up to 6 cycles followed by Maintenance Therapy with Durvalumab|
|Masking:||None (Open Label)|
|Official Title:||Open Label, Phase II Study of Anti - Programmed Death - Ligand 1 Antibody, Durvalumab (MEDI4736), in Combination With Chemotherapy for the First-Line Treatment of Unresectable Mesothelioma|
|Actual Study Start Date :||June 13, 2017|
|Actual Primary Completion Date :||February 16, 2020|
|Estimated Study Completion Date :||June 2023|
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).
On Day 1 of each 21 day cycle: Durvalumab 1120 mg IV will be administered before pemetrexed and cisplatin chemotherapy over approximately 60 minutes. Approximately 30 minutes after the durvalumab infusion is complete, pemetrexed 500 mg/m² IV will be administered over 10 minutes. Cisplatin 75 mg/m² IV over 2 hours will begin approximately 30 minutes after the end of pemetrexed administration. If carboplatin is substituted for cisplatin, carboplatin Area Under the Concentration-Time Curve (AUC) 5 will be infused over 30 minutes beginning approximately 15-30 minutes after the end of the pemetrexed administration. Maintenance: On Day 1 of each 21 day cycle: Durvalumab 1120 mg IV over approximately 60 minutes.
Other Name: MEDI4736
- Overall Survival (OS) [ Time Frame: 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.
- Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: From randomization until end of treatment, up to 15 months ]ORR assessed in accordance with RECIST 1.1 (modified for malignant mesothelioma).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02899195
|Study Chair:||Patrick Forde, MD||John Hopkins|