NCT01675765

Safety and Efficacy of Listeria in Combination With Chemotherapy as Front-line Treatment for Malignant Pleural Mesothelioma

A Phase 1B Study to Evaluate the Safety and Induction of Immune Response of CRS-207 in Combination With Pemetrexed and Cisplatin as Front-line Therapy in Adults With Malignant Pleural Mesothelioma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 60 (actual)
• Sponsor: Aduro Biotech, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This clinical trial will evaluate the safety and immune response of the sequential administration cancer vaccine CRS-207 (with or without cyclophosphamide) followed by standard of care chemotherapy (pemetrexed and cisplatin). CRS-207 is a weakened (attenuated) form of Listeria monocytogenes that has been genetically-modified to reduce its capacity to cause disease, while maintaining its ability to stimulate potent immune responses. CRS-207 has been engineered to elicit an immune response against the tumor-associated antigen mesothelin, which has been shown to be present at higher levels on certain tumor cells (such as mesothelioma) than on normal cells. Pemetrexed and cisplatin are the standard chemotherapy regimen to treat malignant pleural mesothelioma. This trial will evaluate whether giving CRS-207 cancer vaccine with chemotherapy will induce anti-tumor immune responses and/or objective tumor response.

Detailed description

Up to 60 subjects will be enrolled in this study. Eligible subjects will receive 2 prime vaccinations of CRS-207 (1×10\^9 colony-forming units \[CFU\] given intravenously \[i.v.\] over 2 hours) (with or without cyclophosphamide) 2 weeks apart followed 2 weeks later by up to 6 cycles of pemetrexed and cisplatin 21 days apart. Three weeks after completion of chemotherapy, subjects will receive an additional 2 infusions (boost vaccinations) of CRS-207 3 weeks apart. Subjects will be followed every 8 weeks until disease progression by immune-related response criteria. Subjects who continue to meet dosing eligibility may receive additional CRS-207 (with or without cyclophosphamide) infusions (maintenance vaccinations) at each follow-up visit. Study assessments include blood draws for safety and immune response monitoring and CT scans \[with optional fluorodeoxyglucose positron emission tomography (FDG-PET)\] or magnetic resonance imaging (MRI) to monitor disease status. In addition, optional tumor biopsies may be performed before, during and after treatment.

Conditions

• Malignant Pleural Mesothelioma

Interventions

Type	Name	Description
BIOLOGICAL	Immunotherapy plus chemotherapy	live attenuated double deleted Lm
BIOLOGICAL	Immunotherapy with cyclophosphamide plus chemotherapy	live attenuated double deleted Lm

Timeline

• Start date: 2014-09-03
• Primary completion: 2018-09-05
• Completion: 2019-08-19
• First posted: 2012-08-30
• Last updated: 2020-09-30
• Results posted: 2020-09-30

Locations

5 sites across 1 country: United States