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

Study Overview
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Brief Summary
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This trial studies the side effects of pembrolizumab with or without chemotherapy in treating patients with stage IV non-small cell lung cancer that has come back (recurrent) and has spread to other places in the body (advanced). 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. Drugs used in chemotherapy, such as pemetrexed and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab with or without chemotherapy may shrink the tumor in older patients with non-small cell lung cancer.

Detailed Description
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The primary and secondary objectives of the study: PRIMARY OBJECTIVE: I. To estimate the adverse event profile of MK-3475 (pembrolizumab) in non-small cell lung cancer patients who are age 70 years of age or older and who are treated with MK-3475 (pembrolizumab) +/- chemotherapy in a first-line setting. SECONDARY OBJECTIVES: I. To estimate overall survival. II. To describe patient quality of life during the treatment using the Linear Analogue Self-Assessment (LASA) questionnaire. III. 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. 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 days in the absence of disease progression or unacceptable toxicity. GROUP B: Patients receive pembrolizumab IV over 30 minutes, pemetrexed IV over 10 minutes, and carboplatin IV per institutional guidelines on day 1. Cycles 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.

Official Title
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Older Non-Small Cell Lung Cancer Patients (>/= 70 Years of Age) Treated With First-Line MK-3475 (Pembrolizumab)+/- Chemotherapy (Oncologist's/Patient's Choice)

Conditions
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Metastatic Lung Adenocarcinoma, Metastatic Lung Non-Small Cell Carcinoma, Recurrent Lung Adenocarcinoma, Recurrent Lung Non-Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8

Intervention / Treatment
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* Drug: Pembrolizumab
* Drug: Pemetrexed
* Drug: Carboplatin
* Other: Comprehensive Geriatric Assessment
* Other: Questionnaire Administration
* Other: Quality-of-Life Assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 or 400 mg IV every 42 days. MK-3475 (pembrolizumab) 200 mg IV or 400 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

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A (pembrolizumab)<br>Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. | Drug: Pembrolizumab<br>* Given IV<br>Other: Comprehensive Geriatric Assessment<br>* Ancillary studies<br>Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>|
| Experimental: Group B (pembrolizumab, pemetrexed, carboplatin)<br>Patients receive pembrolizumab IV over 30 minutes, pemetrexed IV over 10 minutes, and carboplatin IV per institutional guidelines on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. | Drug: Pembrolizumab<br>* Given IV<br>Drug: Pemetrexed<br>* Given IV<br>Drug: Carboplatin<br>* Given IV<br>Other: Comprehensive Geriatric Assessment<br>* Ancillary studies<br>Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of grade 3 or worse adverse events post registration | Assessed by National Cancer Institute Common Terminology Criteria in Adverse Events version 5.0. The proportion of patients experience grade 3 or worse adverse events (AEs) will be summarized by frequency and percentage along with a 95% confidence interval (CI) separately by type of therapy (monotherapy or combination therapy) as well as combining the two cohorts. All other individual AEs will be analyzed in an exploratory and hypothesis generating manner; including and not limited to multi-variate logistic regression models considering the baseline demographics and the presence/absence of the AE. | Up to 7 days of last day of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Will be summarized using the Kaplan-Meier estimator, separately by monotherapy or combination therapy as well as by the combined cohort. | From study registration to death or the last follow-up whichever occurs first, assessed up to 5 years | 
| Quality of life (QOL): Linear Analogue Self-Assessment [LASA] questionnaire | The overall quality of life score (the first question of the Linear Analogue Self-Assessment [LASA] questionnaire) at each time point as well as change from baseline will be summarized by mean (standard deviation), median (range) along with a longitudinal plot. The median quality of life (QOL) change from baseline along with a 95% confidence interval (CI) will be estimated using the Hodges-Lehmann method. The overall quality of life score will be measured on a scale from 0-10, with higher being better. | Up to 5 years | 
| Comprehensive geriatric assessment risk score | The geriatric risk score, measured as low, medium, or high, will be summarized in a 3X2 frequency table with adverse events. | At baseline |