Pilot Study of Performance Status 2 vs. Performance Status 0-1 Non-small Cell Lung Cancer Patients Treated With Chemo/Immunotherapy

Official title

Phase II Pilot Study of Performance Status 2 vs. Performance Status 0-1 Non-Small Cell Lung Cancer Patients Treated With Chemo/Immunotherapy

Overview

This pilot study is configured as a non-inferiority comparison of Performance Status 2 patients with Performance Status 0-1 patients, with the goal of demonstrating non-inferiority in terms of efficacy (progression-free survival, overall survival) and safety (rates of adverse events, quality of life) when treating Performance Status 2 patients with the same first-line immunotherapy-based regimen as Performance Status 0-1 patients.

Detailed description

Primary Objective: To demonstrate that proportion of Performance Status 2 participants with progression-free survival at 12 weeks is not inferior to the corresponding proportion of Performance Status 0-1 patients.

Secondary Objective(s)

* To demonstrate that incidence of treatment-related adverse events at 12 weeks in the Performance Status 2 group is not higher than that occurring in the Performance Status 0-1 groups. * To demonstrate that change in overall quality of life/global health status at 12 weeks is not inferior in the Performance Status 2 group compared to the change in the Performance Status 0-1 group. * To demonstrate that proportion of participants with deterioration in lung-cancer specific symptoms at 12 weeks in the Performance Status 2 group is not higher than the corresponding proportion in the Performance Status 0-1 group.

Interventions

• Drug Pembrolizumab
  ALL PARTICIPANTS: Pembrolizumab 200 mg intravenously (IV) on day 1 of each 3-week cycle for 4 cycles. Participants with predictive biomarker PD-L1 greater than or equal to 50% will not receive any other drugs besides pembrolizumab.
• Drug Carboplatin
  FOR PARTICIPANTS IN EITHER ARM with non-squamous OR squamous subtype, predictive biomarker PD-L1 less than 50%: Carboplatin area under the curve (AUC) 5 IV on day 1 of each 3-week cycle for 4 cycles.
• Drug Paclitaxel
  FOR PARTICIPANTS IN EITHER ARM with squamous subtype, predictive biomarker PD-L1 less than 50%: Paclitaxel 200 mg/m2 IV on day 1 of each 3-week cycle for 4 cycles.
• Drug Nab paclitaxel
  FOR PARTICIPANTS IN EITHER ARM with squamous subtype, predictive biomarker PD-L1 less than 50%: Nab-paclitaxel 100 mg/m2 on day 1, 8, 15 of 3-week cycle for 4 cycles.
• Other Quality of Life Questionnaire, lung cancer-specific (QLQ-LC13)
  The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items.
• Other QLQ-C30 Global Health/Quality of Life Questionnaire
  30 item questionnaire - Functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, and nausea and vomiting), global health status and quality of life scale, also several single-item symptom measures
• Other COPD Assessment Test and modified Medical Research Council Dyspnea Patient Reported Outcomes
  Dyspnea scale scores in patients with respiratory disease (particularly COPD) to establish baseline functional dyspnea burden (taken pre-study at Week 0 and Post Treatment at week 13)
• Drug Pemetrexed
  FOR PARTICIPANTS IN EITHER ARM with nonsquamous subtype, predictive biomarker PD-L1 less than 50%: Pemetrexed 500 mg/m2 IV on day 1 of each 3-week cycle for 4 cycles.

Primary outcome measures

• Proportion of Participants with Progression-Free Survival [Time frame: From baseline to end of 4th cycle of treatment (12 weeks)]

Secondary outcome measures (3)

• Incidences of Grade 3 to Grade 5 Treatment-Related Adverse Events [Time frame: 12 weeks]
• Change in Overall Quality of Life/Global Health Status - EORTC QLQ-C30 [Time frame: From baseline to end of 4th cycle of treatment (12 weeks)]
• Proportion of Participants with Deterioration in Symptoms - QLQ-LC13 [Time frame: From baseline to end of 4th cycle of treatment (12 weeks)]

Eligibility criteria

Inclusion criteria

• Patients must have a cytological or histological diagnosis of non-small cell lung cancer that is metastatic or unresectable for which standard curative 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.
• At least 18 years old.
• 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 normal organ and marrow function as defined below:
• 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 IRB-approved informed consent document.

Exclusion criteria

• Nonsmall cell lung cancer that is known at registration to be positive for a tumor activating alteration for which first line targeted therapy is indicated9; 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). For non-squamous subtypes, molecular testing of tumor and peripheral blood should be attempted for actionable biomarkers, but if there is an insufficient quantity of tumor material for testing and it is not feasible to attempt additional biopsies before starting systemic therapy, then these biomarker results are not necessary for inclusion on the study. For squamous subtype, molecular testing should be considered but is not necessary for inclusion on the study.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Wake Forest Baptist Comprehensive Cancer Center — Winston-Salem

Identifiers

NCT: NCT04253964 · IRB00063540 · WFBCCC 62619 · P30CA012197

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗