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

NCT ID: NCT04253964

Last Updated: 2025-07-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-01
• Study Completion Date: 2026-03-31

Brief Summary

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.

Conditions

Nonsmall Cell Lung Cancer; Performance Status

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Performance Status 0-1 Participants

ALL study participants will receive pembrolizumab 200 mg intravenously (IV) on day 1 of each 3-week cycle.

Participants with predictive biomarker PD-L1 greater than or equal to 50%: Participants will not receive any other drugs besides pembrolizumab.

Participants with Non-squamous subtype, predictive biomarker (PD-L1 less than 50%): Participants will ALSO receive:

• Carboplatin area under the curve (AUC) 5 IV on day 1 of each 3-week cycle for 4 cycles.

PLUS

• Pemetrexed 500 mg/m2 IV on day 1 of each 3-week cycle for 4 cycles.

Participants with Squamous subtype, predictive biomarker (PD-L1 less than 50%): Participants will also receive:

• Carboplatin AUC 5 IV on day 1 of each 3-week cycle for 4 cycles. PLUS
• Paclitaxel 200 mg/m2 IV on day 1 of each 3-week cycle for 4 cycles. OR
• Nab-paclitaxel 100 mg/m2 on day 1, 8, 15 of 3-week cycle for 4 cycles

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: DRUG

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.

Carboplatin

Intervention Type: DRUG

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.

Paclitaxel

Intervention Type: DRUG

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.

Nab paclitaxel

Intervention Type: DRUG

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.

Quality of Life Questionnaire, lung cancer-specific (QLQ-LC13)

Intervention Type: OTHER

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.

QLQ-C30 Global Health/Quality of Life Questionnaire

Intervention Type: OTHER

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

COPD Assessment Test and modified Medical Research Council Dyspnea Patient Reported Outcomes

Intervention Type: OTHER

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)

Pemetrexed

Intervention Type: DRUG

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.

Performance Status 2 Participants

ALL study participants will receive pembrolizumab 200 mg intravenously (IV) on day 1 of each 3-week cycle.

Participants with predictive biomarker PD-L1 greater than or equal to 50%: Participants will not receive any other drugs besides pembrolizumab.

Participants with Non-squamous subtype, predictive biomarker (PD-L1 less than 50%): Participants will ALSO receive:

• Carboplatin area under the curve (AUC) 5 IV on day 1 of each 3-week cycle for 4 cycles.

PLUS

• Pemetrexed 500 mg/m2 IV on day 1 of each 3-week cycle for 4 cycles.

Participants with Squamous subtype, predictive biomarker (PD-L1 less than 50%): Participants will also receive:

• Carboplatin AUC 5 IV on day 1 of each 3-week cycle for 4 cycles. PLUS
• Paclitaxel 200 mg/m2 IV on day 1 of each 3-week cycle for 4 cycles. OR
• Nab-paclitaxel 100 mg/m2 on day 1, 8, 15 of 3-week cycle for 4 cycles

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: DRUG

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.

Carboplatin

Intervention Type: DRUG

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.

Paclitaxel

Intervention Type: DRUG

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.

Nab paclitaxel

Intervention Type: DRUG

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.

Quality of Life Questionnaire, lung cancer-specific (QLQ-LC13)

Intervention Type: OTHER

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.

QLQ-C30 Global Health/Quality of Life Questionnaire

Intervention Type: OTHER

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

COPD Assessment Test and modified Medical Research Council Dyspnea Patient Reported Outcomes

Intervention Type: OTHER

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)

Pemetrexed

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

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.

Intervention Type: 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

Intervention Type: 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)

Intervention Type: OTHER

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.

Intervention Type: DRUG

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 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). 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Lycan, Jr., D.O., M.H.S.

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Locations

Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Principal Investigator

Role: CONTACT

tlycan@wakehealth.edu

336-713-5440

Facility Contacts

Study Nurse

Role: primary

saverill@wakehealth.edu

Other Identifiers

WFBCCC 62619

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA012197

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00063540

Identifier Type: -

Identifier Source: org_study_id