Study of Pembrolizumab With Single Agent Chemotherapy in Elderly Patients With Advanced NSCLC

NCT04754815 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: HFHS 21-01
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This Phase II trial is to see how well single agent chemotherapy and pembrolizumab work elderly patients (≥ 75 years) with advanced non small cell lung cancer (NSCLC). Pembrolizumab stimulates your immune system to help fight lung cancer. This treatment approach may be better tolerated in elderly patients.

Conditions

Non Small Cell Lung Cancer; Advanced Lung Non-Small Cell Carcinoma; PD-L1 Gene Mutation

Outcome Measures

Primary Outcomes (1)

• Median progression free survival

  Length of time treatment to disease progression

  6 months

Secondary Outcomes (1)

• Overall survival

  12 months

Study Arms (2)

Pembrolizumab + Pemetrexed

EXPERIMENTAL

Pembrolizumab 200mg intravenous (IV) infusion on Day 1 of each 21 day cycle. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity + pemetrexed 500mg intravenous (IV) infusion (with vitamin supplementation) on Day 1 of each 21 day cycle up to 35 cycles or until disease progression.

Drug: Pembrolizumab; Drug: Pemetrexed; Other: Laboratory Biomarker Analysis

Pembrolizumab + Paclitaxel OR Paclitaxel

EXPERIMENTAL

Pembrolizumab 200mg intravenous (IV) infusion on Day 1 of each 21 day cycle. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity \+ Paclitaxel 100 mg/m2 intravenous (IV) infusion on days 1 and 8 of each 21 day treatment cycle OR Paclitaxel100 mg/m2 intravenous (IV) infusion on days 1 and 8 of each 21 day treatment cycle until disease progression.

Drug: Pembrolizumab; Drug: Paclitaxel; Drug: Nab-paclitaxel; Other: Laboratory Biomarker Analysis

Interventions

Pembrolizumab DRUG

PD-L1 inhibitor administered as an intravenous (IV) infusion.

Also known as: Keytruda

Pembrolizumab + Paclitaxel OR Paclitaxel; Pembrolizumab + Pemetrexed

Pemetrexed DRUG

Folate analog metabolic inhibitor administered as an intravenous (IV) infusion single agent chemotherapy for advanced NSCLC

Also known as: ALIMTA

Pembrolizumab + Pemetrexed

Paclitaxel DRUG

A novel antimicrotubular agent administered as an intravenous (IV) infusion single agent chemotherapy for advanced NSCLC

Also known as: TAXOL

Pembrolizumab + Paclitaxel OR Paclitaxel

Nab-paclitaxel DRUG

Microtubule inhibitor administered as an intravenous (IV) infusion indicated for the treatment of locally advanced or metastatic NSCLC

Also known as: ABRAXANE®

Pembrolizumab + Paclitaxel OR Paclitaxel

Laboratory Biomarker Analysis OTHER

Correlative studies

Pembrolizumab + Paclitaxel OR Paclitaxel; Pembrolizumab + Pemetrexed

Eligibility Criteria

• Age: 75 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Male/female participants who are ≥75 years of age on the day of signing informed consent with histologically confirmed diagnosis of stage IV (AJCC version 8) NSCLC with tumor PD-L1 \< 50% and negative 'driver' alterations in EGFR, ALK and ROS1 will be enrolled in this study. Tumor PD-L1 expression should be assessed by FDA approved Dako 22C3 test.
• Patients should be treatment naïve for stage IV NSCLC. Patients previously treated for earlier stages of lung cancer are eligible if they have not received systemic therapy for a minimum of 180 days prior to the start of study therapy.
• The participant provides written informed consent for the trial.
• Have measurable disease based on RECIST 1.1 or evaluable disease.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0,1. Evaluation of ECOG is to be performed within 7 days prior to the date of start of therapy.
• Male participants:
• A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period.
• Have adequate organ function as evidenced by laboratory assessment. Specimens must be collected within 10 days prior to the start of study treatment.

You may not qualify if:

• Patient could not have received any anti-cancer systemic therapy for a minimum of 180 days prior to the start of study therapy. Patient should not have received prior PD-1 or PD-L1 therapy.
• Has received prior definitive palliative radiotherapy within 2 weeks or definitive radiotherapy within 6 months of study intervention. Participants must have recovered from all radiation-related toxicities, require corticosteroids no more than 10 mg of prednisone or equivalent dose of other steroids, and not have had clinical radiation pneumonitis.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. Patients with cancers such as PSA only prostate cancer may be considered after discussion with the principal investigator.
• Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in-situ cancers
• Has symptomatic CNS metastases and/or carcinomatous meningitis. Subjects with asymptomatic brain metastases may participate provided they are clinically stable and are not using steroids equivalent to \>10mg of prednisone day prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of whether it is symptomatic or not.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV testing is required unless mandated by local health authority.
• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
• Has a known history of active TB (Bacillus Tuberculosis).

Sponsors & Collaborators

• Shirish Gadgeel: lead
• Merck Sharp & Dohme LLC: collaborator

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; Pemetrexed; Paclitaxel; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins

Study Officials

• Shirish Gadgeel, MBBS

  Henry Ford Health System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principle Investigator

Model Details: Single arm open label with 2 treatment options

Study Record Dates

• First Submitted: February 10, 2021
• First Posted: February 15, 2021
• Study Start: April 1, 2021
• Primary Completion: April 1, 2025
• Study Completion: April 1, 2026
• Last Updated: March 29, 2022

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share