Phase I Trial of Adjuvant Pembrolizumab After Radiation Therapy for Lung-Intact Malignant Pleural Mesothelioma
Overview
- Phase
- Phase 1
- Intervention
- Laboratory Biomarker Analysis
- Conditions
- Pleural Malignant Mesothelioma
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Safety/Toxicity
- Status
- Active, not recruiting
- Last Updated
- last month
Overview
Brief Summary
This phase I trial studies the side effects and best way to give pembrolizumab after radiation therapy in treating patients with pleural malignant mesothelioma. Radiation therapy uses high energy radiation to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving pembrolizumab after radiation therapy may kill more tumor cells.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the safety and tolerability of pembrolizumab administered after radiation therapy in patients with malignant pleural mesothelioma (MPM) who have not undergone extrapleural pneumonectomy. SECONDARY OBJECTIVES: I. To assess progression-free and overall survival (progression free survival \[PFS\] and overall survival \[OS\], respectively) in patients receiving pembrolizumab after radiation therapy for malignant pleural mesothelioma (MPM). EXPLORATORY OBJECTIVES: I. To evaluate biomarkers of interest, including cytokines, measurements of T-cell activation, and serum exosome micro ribonucleic acid (RNA)s with the delivery of pembrolizumab after radiation therapy for MPM. OUTLINE: Patients are assigned to 1 of 2 cohorts. COHORT 1: Patients undergo hemithoracic radiation therapy. COHORT 2: Patients undergo palliative radiation therapy over 1-3 weeks to only the region of palliation (a region that does not include the entire side of the chest or thorax). After radiation therapy, both cohorts receive pembrolizumab intravenously (IV) over about 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, every 6 weeks for 48 weeks, then every 12 weeks for up to 5 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have a histologic diagnosis of malignant pleural mesothelioma, with histologic diagnosis from the pleura or relevant lymph node stations, including mediastinal, hilar, or supraclavicular lymph nodes
- •Be willing and able to provide written informed consent/assent for the trial
- •Have measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; however, note that patients in Cohort 1 that have undergone an R0 resection will be eligible for the trial
- •Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
- •Absolute neutrophil count (ANC) \>=1,500 /mcL (within 10-15 days of treatment initiation)
- •Platelets \>= 100,000 /mcL (within 10-15 days of treatment initiation)
- •Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) (within 10-15 days of treatment initiation)
- •Serum creatinine =\< 1.5 X upper limit of normal (ULN) or measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN (within 10-15 days of treatment initiation)
- •Serum total bilirubin =\< 1.5 X ULN or direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN (within 10-15 days of treatment initiation)
- •Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) =\< 2.5 X ULN or =\< 5 X ULN for subjects with liver metastases (within 10-15 days of treatment initiation)
Exclusion Criteria
- •Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
- •Has a diagnosis of immunodeficiency; note that patients should not receive steroids during pembrolizumab administration
- •Has a known history of active tuberculosis (TB) (Bacillus tuberculosis)
- •Hypersensitivity to pembrolizumab or any of its excipients
- •Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
- •Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 and who have not recovered adequately from this treatment (=\< grade 2 toxicity at the time of enrollment)
- •Has a known additional malignancy that is progressing or requires active treatment; patients with a stage I-III cancer that has been cured over two years ago are not excluded in the study
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
- •Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- •Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
Arms & Interventions
Cohort 1 (hemithoracic radiation therapy, pembrolizumab)
Patients undergo hemithoracic radiation therapy. After radiation therapy, patients receive pembrolizumab IV over about 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Cohort 1 (hemithoracic radiation therapy, pembrolizumab)
Patients undergo hemithoracic radiation therapy. After radiation therapy, patients receive pembrolizumab IV over about 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Intervention: Pembrolizumab
Cohort 1 (hemithoracic radiation therapy, pembrolizumab)
Patients undergo hemithoracic radiation therapy. After radiation therapy, patients receive pembrolizumab IV over about 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Intervention: Radiation Therapy
Cohort 2 (palliative radiation therapy, pembrolizumab)
Patients undergo palliative radiation therapy over 1-3 weeks to only the region of palliation (a region that does not include the entire side of the chest or thorax). After radiation therapy, patients receive pembrolizumab IV over about 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Cohort 2 (palliative radiation therapy, pembrolizumab)
Patients undergo palliative radiation therapy over 1-3 weeks to only the region of palliation (a region that does not include the entire side of the chest or thorax). After radiation therapy, patients receive pembrolizumab IV over about 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Intervention: Palliative Radiation Therapy
Cohort 2 (palliative radiation therapy, pembrolizumab)
Patients undergo palliative radiation therapy over 1-3 weeks to only the region of palliation (a region that does not include the entire side of the chest or thorax). After radiation therapy, patients receive pembrolizumab IV over about 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Safety/Toxicity
Time Frame: Baseline to 4-months after the start of radiation therapy
To determine the safety and tolerability of pembrolizumab administered after radiation therapy in patients with MPM. The primary endpoint was "unaccepable" high grade adverse events (AEs) from baseline to 4-month after the start of radiation therapy.
Secondary Outcomes
- Overall Survival (OS)(Every 6 weeks (42 +/- 7 days) until to 48 weeks, then every 12 weeks (+/- 7 days) to 5 years)
- Progression-Free Survival (PFS)(Every 6 weeks (42 +/- 7 days) until to 48 weeks, then every 12 weeks (+/- 7 days) to 5 years)