Phase I Trial of Adjuvant Pembrolizumab After Radiation Therapy for Lung-Intact Malignant Pleural Mesothelioma
Phase I Trial of Adjuvant Pembrolizumab After Radiation Therapy for Lung-Intact Malignant Pleural Mesothelioma
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.
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.
Inclusion Criteria:
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
Has an active infection requiring systemic therapy
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
Has received a live vaccine within 30 days of planned start of study therapy
Evidence of interstitial lung disease
COHORT 1 EXCLUSION CRITERIA
Patients undergoing an extrapleural pneumonectomy (EPP); lung sparing surgeries, such as pleurectomy/decortication, are acceptable
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
COHORT 2 EXCLUSION CRITERIA
Patients in which hemithoracic radiation therapy is planned
Patients who have received EPP for mesothelioma
COHORTS 1 AND 2 EXCLUSION CRITERIA
Patients with inherited syndromes associated with hypersensitivity to ionizing radiation, specifically patients with known history of ataxia-telengiectasia, Nijmegen breakage syndrome