Neoadjuvant Durvalumab and Tremelimumab With and Without Chemotherapy for Mesothelioma
ConditionMesothelioma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorBaylor College of Medicine
About this trial
Objectives: The investigators will test whether combination of chemoimmunotherapy or dual agent immunotherapy alone improves efficacy for patients with MPM.
Primary Objectives:
The primary objective is to test whether the combination of platinum-based chemotherapy and pemetrexed with durvalumab / tremelimumab or durvalumab / tremelimumab alone improves recurrence-free survival for patients with resectable MPM compared to historical, published data for surgery with chemotherapy.
Secondary Objective(s):
The secondary objectives are to determine the safety of and whether the platinum-based chemotherapy and pemetrexed with durvalumab / tremelimumab or durvalumab / tremelimumab alone improves response rate, resectability, major pathological response, and complete pathological response.
Exploratory Objective(s):
The exploratory objectives are to determine the safety of and whether the platinum-based chemotherapy and pemetrexed with durvalumab / tremelimumab or durvalumab / tremelimumab alone improves response rate, resectability, major pathological response, and complete pathological response for patients with epithelioid and non-epithelioid histologies.
The scientific exploratory objectives include:
1. Develop an NGS plasma assay of common mutations identified from our previous grant cycle to prospectively measure minimal residual disease (MRD) after resection as a potential, novel biomarker test in mesothelioma. 2. Determine the predictive role of BH3 profiling in patients undergoing neoadjuvant ICI followed by surgery: With patient samples collected from our neoadjuvant ICI trial, the investigators will test whether BH3 profiling from pre-treatment tumor biopsies and PBMC predicts clinical, radiological, and pathological responses to ICIs. The investigators will identify TAMs from the TiME in MPM tumor samples before and after treatment to compare differences in polarization induced by ICI in clinical and pathologically responding versus non-responding patients.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Potentially Surgically resectable MPM. Computed tomography (CT) and positron emission tomography (PET) without disease beyond ipsilateral hemithorax. CT and PET scan without obvious invasion through the chest wall or mediastinum. Surgical evaluation for resectability by an experienced mesothelioma surgeon to assess whether tumor appears resectable on CT and PET. (Final resectability determination is based on intra-operative exploratory thoracotomy to assess chest wall and/or mediastinal invasion that is not apparent based on pre-operative radiological assessment. Given this assessment after enrollment, this determination will be utilized for the safety phase). Based on above criteria, patients will undergo planned resectional surgery for MPM [extrapleural pneumonectomy (EPP) or pleurectomy and decortication (P/D)]
Any MPM histology (epithelial, mixed, sarcomatoid)
N0 or N1 nodal disease, as present on preoperative chest CT and/or PET/CT
N2 nodal disease.
Disqualifiers
Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) or previous enrollment or randomization in the present study.
Participation in another clinical study with an investigational product during the last 3 months.
Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab.
Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, or other investigational agent) <28 days
Trial design
Design model
Parallel
Treatments tested in this trial
Durvalumab / tremelimumab
DrugDurvalumab concentrate for solution for infusion will be supplied in glass vials containing 500 mg durvalumab at a concentration of 50 mg/mL. Tremelimumab concentrate for solution for infusion will be supplied in glass vials containing 400 mg or 25 mg tremelimumab at a concentration of 20 mg/mL.
Platinum cisplatin or carboplatin and pemetrexed chemotherapy plus durvalumab/tremelimumab
DrugCisplatin 75mg/ m2 (or carboplatin AUC 5-6) + pemetrexed 500 mg/m2 will be provided as per standard of care. Durvalumab concentrate for solution for infusion will be supplied in glass vials containing 500 mg durvalumab at a concentration of 50 mg/mL. Tremelimumab concentrate for solution for infusion will be supplied in glass vials containing 400 mg or 25 mg tremelimumab at a concentration of 20 mg/mL.
Treatment groups
52 Participants
are divided into 2 treatment groupsGroup A: Induction dual immunotherapy with durvalumab / tremelimumabExperimental treatment 1 intervention
Group B: Platinum cisplatin or carboplatin and pemetrexed chemotherapy plus durvalumab/tremelimumabExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Recurrence-free survival of greater than 60% at one year.
Recurrence-free survival of greater than 60% at one year.
Time frame
Recurrence-free survival of greater than 60% at one year.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Baylor College of Medicine
Lead sponsor
Duke Cancer Institute
Collaborator
Source ClinicalTrials.gov