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Pembrolizumab with or without Chemotherapy for the Treatment of Non-small Cell Lung Cancer

Trial Status: Active

This phase II trial studies how well pembrolizumab with or without chemotherapy works in treating patients with non-small cell lung cancer that have a performance status of 2 compared to a performance status of 0-1. Performance status is a measure used by doctors to describe how much cancer has impacted a patient’s daily living abilities. 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. Chemotherapy drugs, such as carboplatin, pemetrexed, paclitaxel, and nab-paclitaxel, 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. The purpose of this research is to see whether or not the standard treatment regimen of immunotherapy, with or without chemotherapy, can help patients who are less physically functional as much as it helps patients who are more physically functional.

Inclusion Criteria

  • Patients must have histologically confirmed non-small cell lung cancer (NSCLC) that is metastatic or unresectable and for which standard curative or palliative measures do not exist
  • No prior systemic treatment with either chemotherapy or immunotherapy for non-curative intent. Patients may have previously received cancer treatment with curative intent for prior early stage disease
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, as determined by the treating physician in the consult note
  • Life expectancy of greater than 3 months
  • Patients must have radiographically measurable metastatic disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
  • Absolute neutrophil count >= 1,000/mcL
  • Platelets >= 100,000/mcL
  • Chemotherapy agents are known to be teratogenic, therefore women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document

Exclusion Criteria

  • NSCLC that is known at registration to be positive for a tumor activating alteration for which first line targeted therapy is indicated; specifically, a targetable mutation in epidermal growth factor receptor (EGFR), gene rearrangement of anaplastic lymphoma kinase (ALK), gene rearrangement of c-ros oncogene 1 (ROS1), or mutation in B isoform of rapidly accelerated fibrosarcoma (B-Raf)
  • Known to have an active autoimmune disease that required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, systemic corticosteroids, or immunosuppressive drugs)
  • History of (non-infectious) pneumonitis that required systemic corticosteroids
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects with chemotherapy. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with chemotherapy, breastfeeding should be discontinued

North Carolina

Winston-Salem
Wake Forest University Health Sciences
Status: ACTIVE
Contact: Thomas William Lycan
Phone: 336-716-0230

PRIMARY OBJECTIVE:

I. To demonstrate that proportion of performance status 2 (PS 2) participants with progression-free survival at 12 weeks is not inferior to the corresponding proportion of PS 0-1 patients.

SECONDARY OBJECTIVES:

I. To demonstrate that incidence of treatment-related adverse events at 12 weeks in the PS 2 group is not higher than that occurring in the PS 0-1 groups.

II. To demonstrate that change in overall quality of life (QOL)/global health status (GHS) at 12 weeks is not inferior in the PS 2 group compared to the change in the PS 0-1 group.

III. To demonstrate that proportion of participants with deterioration in lung-cancer specific symptoms at 12 weeks in the PS 2 group is not higher than the corresponding proportion in the PS 0-1 group.

EXPLORATORY OBJECTIVES:

I. To examine whether overall response rate is non-inferior in the PS 2 group compared to the PS 0-1 group.

II. To examine whether median overall survival is non-inferior in the PS 2 group compared to the PS 0-1 group.

III. To examine whether change in lung-cancer-specific QOL measures at 12 weeks is non-inferior in the PS 2 group compared to the PS 0-1 group.

IV. To examine whether change in chronic obstructive pulmonary disease (COPD) functional status 12 weeks is non-inferior in the PS 2 group compared to the PS 0-1 group.

V. To collect serum samples from pre-treatment, post-treatment, and follow-up for future studies of laboratory correlatives.

OUTLINE: Patients are assigned to 1 of 3 arms.

ARM I: Patents with PD-L1 >= 50% receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeat every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients with PD-L1 < 50% and non-squamous non-small cell lung cancer (NSCLC) sub type receive pembrolizumab IV over 30 minutes, carboplatin IV, and pemetrexed IV on day 1. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

ARM III: Patients with PD-L1 < 50% squamous NSCLC sub type receive pembrolizumab IV over 30 minutes and carboplatin IV on day 1. Patients also receive paclitaxel IV on day 1 OR nab-paclitaxel IV on days 1, 8, and 15. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

After the completion of study treatment, patients are followed up for 30 days, then up to 3 months.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Wake Forest University Health Sciences

Principal Investigator
Thomas William Lycan

  • Primary ID WFBCCC 62619
  • Secondary IDs NCI-2020-03137
  • Clinicaltrials.gov ID NCT04253964