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

Phase 2

Active, not recruiting

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

Interventions: Drug: Pembrolizumab
Other: Comprehensive Geriatric Assessment
Drug: Pemetrexed
Other: Questionnaire Administration
Drug: Carboplatin
Other: Quality-of-Life Assessment

Registration Number: NCT04533451

Lead Sponsor: Alliance for Clinical Trials in Oncology

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 101

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A (pembrolizumab)	Quality-of-Life Assessment	Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Group B (pembrolizumab, pemetrexed, carboplatin)	Quality-of-Life Assessment	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.
Group A (pembrolizumab)	Questionnaire Administration	Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Group A (pembrolizumab)	Comprehensive Geriatric Assessment	Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Group B (pembrolizumab, pemetrexed, carboplatin)	Comprehensive Geriatric Assessment	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.
Group B (pembrolizumab, pemetrexed, carboplatin)	Questionnaire Administration	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.
Group B (pembrolizumab, pemetrexed, carboplatin)	Carboplatin	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.
Group A (pembrolizumab)	Pembrolizumab	Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Group B (pembrolizumab, pemetrexed, carboplatin)	Pemetrexed	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.
Group B (pembrolizumab, pemetrexed, carboplatin)	Pembrolizumab	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.

Primary Outcome Measures

Name	Time	Method
Incidence of Grade 3 or Worse Adverse Events Post Registration	Up to 7 days of last day of treatment, up to 6 months	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	From study registration to death or the last follow-up whichever occurs first, assessed up to 3 years	Will be summarized using the Kaplan-Meier estimator, separately by monotherapy or combination therapy as well as by the combined cohort.
Quality of Life (QOL): Linear Analogue Self-Assessment [LASA] Questionnaire	Up to 9 weeks	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.
Comprehensive Geriatric Assessment Risk Score	At baseline. Per the protocol section 13.5,Comprehensive geriatric assessment would be examined combined by arm.	The geriatric risk score, measured as low, medium, or high, will be summarized in a 3X2 frequency table with adverse events.

Trial Locations

Locations (505): Anchorage Associates in Radiation Medicine
🇺🇸
Anchorage, Alaska, United States
Anchorage Radiation Therapy Center
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Anchorage, Alaska, United States
Alaska Breast Care and Surgery LLC
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Anchorage, Alaska, United States
Alaska Oncology and Hematology LLC
🇺🇸
Anchorage, Alaska, United States
Alaska Women's Cancer Care
🇺🇸
Anchorage, Alaska, United States
Anchorage Oncology Centre
🇺🇸
Anchorage, Alaska, United States
Katmai Oncology Group
🇺🇸
Anchorage, Alaska, United States
Providence Alaska Medical Center
🇺🇸
Anchorage, Alaska, United States
Fairbanks Memorial Hospital
🇺🇸
Fairbanks, Alaska, United States
Kingman Regional Medical Center
🇺🇸
Kingman, Arizona, United States
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Anchorage Associates in Radiation Medicine
🇺🇸Anchorage, Alaska, United States