Testing the Effects of MK-3475 (Pembrolizumab) with or without the Usual Chemotherapy Treatment for Patients 70 Years of Age and Older with Advanced Non-small Cell Lung Cancer
- Documentation of Disease: Histologic or cytologic diagnosis of non-small cell lung cancer (adenocarcinoma). Stage IV or recurrent metastatic non-small cell lung cancer. No planned initiation of definitive (potentially curative) concurrent chemo-radiation
- Planning to begin MK-3475 (pembrolizumab) treatment within 14 days of registration, with or without combination chemotherapy. Treating physician considers pembrolizumab as appropriate and plans to proceed with one of the following treatment schedules: * MK-3475 (pembrolizumab) 200 mg IV flat dose every 21 days * MK-3475 (pembrolizumab) 200 mg IV + carboplatin area under the curve (AUC) = 5 + pemetrexed 500 mg/m^2 (20% chemotherapy dose reduction is permitted per the discretion of the treating physician)
- Patients will be ineligible if they have an autoimmune disorder, are post-organ transplantation, or are receiving ongoing immunosuppression treatment
- Prior adjuvant therapy is allowed and must have been completed at least 6 months prior to registration
- No planned radiation or other cancer treatment in the 3 months following registration
- No untreated brain metastases. Patients must be off corticosteroids and asymptomatic at registration
- Absolute neutrophil count (ANC) >= 1500/mm^3 (1.5 x 10^9/L)
- Platelet count: >= 100,000/mm^3 (100 x 10^9/L)
- Creatinine >= 30 mL/min* for patients enrolled to pembrolizumab alone and > 45 mL/min for patients enrolled to chemotherapy + pembrolizumab * Calculated using the Cockcroft-Gault formula
- Total serum bilirubin =< 1.5 upper limit of normal (ULN) (< 3 ULN if Gilbert's disease)
- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 3 x ULN (=< 5.0 x ULN if liver metastases present)
- Alkaline phosphatase =< 2.5 x ULN (=< 5 x ULN if bone or liver metastases present)
- Language: Patients must be able to speak and comprehend English in order to complete the mandatory patient-completed measures
West Des Moines
Saint Louis Park
I. To estimate the adverse event profile of MK-3475 (pembrolizumab) over the first six months of treatment, in non-small cell lung cancer patients who are 70 years of age or older and who are treated with MK-3475 (pembrolizumab) +/- chemotherapy in a first-line setting.
I. To disaggregate the adverse events and identify potential causes of individual adverse events.
II. To estimate overall survival.
III. To describe patient quality of life during the treatment using the Linear Analogue Self-Assessment (LASA) questionnaire.
IV. To explore whether Comprehensive Geriatric Assessment (CGA) -derived risk score is able to predict rates of severe adverse events in older cancer patients who receive MK-3475 (pembrolizumab) or MK-3475 (pembrolizumab) + chemotherapy.
I. To describe patient fatigue level as measured with the Multidimensional Fatigue Symptom Inventory – Short Form (MFSI-SF); exercise level using the Godin Leisure Time Exercise Questionnaire (GLTE); and other symptoms and concerns using the LASA questionnaires.
II. To estimate time-to-treatment failure for single-agent MK-3475 (pembrolizumab) and MK-3475 (pembrolizumab) + chemotherapy in older patients.
CORRELATIVE SCIENCE OBJECTIVES:
I. To evaluate whether older patients who experience fatigue or other adverse effects would be correlated with a change of PD-L1 therapy-responsive T cell subset (i.e. CX3CR1+CD11ahighCD8+ T-cells) in their peripheral blood from baseline (prior to therapy) to post therapy.
II. To determine the extent to which MK-3475 (pembrolizumab) demonstrates time dependent decrease in clearance in older adult patients (aged >= 70 years) with non-small cell lung cancer being treated with pembrolizumab monotherapy or in combination with cytotoxic chemotherapy.
III. To determine the intrapatient and interpatient variability in clearance in older adult (>= 70 years) patients with non-small cell lung cancer receiving pembrolizumab monotherapy and when combined with cytotoxic chemotherapy.
IV. To preliminarily explore the correlation between pembrolizumab exposure (AUC) with observed immune related toxicities in this older adult (aged >= 70 years) patient population receiving pembrolizumab monotherapy and when combined with cytotoxic chemotherapy.
OUTLINE: Patients are assigned to 1 of 2 groups.
GROUP A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 or 42 days in the absence of disease progression or unacceptable toxicity.
GROUP B: Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles with pembrolizumab repeat every 21 or 42 days in the absence of disease progression or unacceptable toxicity. Patients also receive pemetrexed IV over 10 minutes, and carboplatin IV per institutional guidelines on day 1. Cycles with pemetrexed and carboplatin repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up annually for up to 5 years after registration.
Trial Phase Phase II
Trial Type Treatment
Alliance for Clinical Trials in Oncology
- Primary ID A171901
- Secondary IDs NCI-2020-00544
- Clinicaltrials.gov ID NCT04533451