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

NCT04253964 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: IRB00063540WFBCCC 62619P30CA012197
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 2

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.

Conditions

Performance Status; Nonsmall Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants with Progression-Free Survival

  Using non-blinded central imaging using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 to define progressive disease. RECIST v 1.1 criteria: * Complete Response (CR): Disappearance of all target lesions. * Partial Response (PR): Decrease by ≥ 30% in sum of longest diameter of target lesions. * Stable Disease (SD): Not meeting criteria for CR, PR, or PD. * Progressive Disease (PD): Increase by ≥ 20% in sum of longest diameter of target lesions or the appearance of one or more new lesions. Participants that did not have radiographically measurable metastatic disease by RECIST criteria before starting treatment, progression is defined as the development of new lesions or by unequivocal progression of existing non-target lesions.

  From baseline to end of 4th cycle of treatment (12 weeks)

Secondary Outcomes (3)

• Incidences of Grade 3 to Grade 5 Treatment-Related Adverse Events

  12 weeks

• Change in Overall Quality of Life/Global Health Status - EORTC QLQ-C30

  From baseline to end of 4th cycle of treatment (12 weeks)

• Proportion of Participants with Deterioration in Symptoms - QLQ-LC13

  From baseline to end of 4th cycle of treatment (12 weeks)

Study Arms (2)

Performance Status 0-1 Participants

EXPERIMENTAL

Participants with non-squamous and squamous predictive biomarker PD-L1 ≥50%: Participants will receive one of the following if their treating physician has opted for single-agent immunotherapy: pembrolizumab, atezolizumab, or cemiplimab-rwlc. Participants with non-squamous and squamous subtype, predictive biomarker PD-L1 ≥50%, and the treating clinician has opted for combination chemo/immunotherapy OR participants with non-squamous and squamous subtype, predictive biomarker PD-L1 1-49% or unknown: Participants will receive one of the following--pembrolizumab, atezolizumab, or cemiplimab-rwlc--and ALSO receive: * Carboplatin OR * Cisplatin PLUS * Pemetrexed (non-squamous subtype only) OR * Paclitaxel (squamous subtype only) OR * Nab-paclitaxel (squamous subtype only)

Drug: Pembrolizumab; Drug: Atezolizumab; Drug: Cemiplimab-Rwlc; Drug: Carboplatin; Drug: Paclitaxel; Drug: Nab paclitaxel; Drug: Pemetrexed; Drug: Cisplatin; Other: Quality of Life Questionnaire, lung cancer-specific (QLQ-LC13); Other: QLQ-C30 Global Health/Quality of Life Questionnaire; Other: COPD Assessment Test and modified Medical Research Council Dyspnea Patient Reported Outcomes; Other: PROMIS and FACT-G Questionnaires; Other: Sleep Disorder Assessments (ISI, Berlin Sleep Questionnaire)

Performance Status 2 Participants

EXPERIMENTAL

Participants with non-squamous and squamous predictive biomarker PD-L1 ≥50%: Participants will receive one of the following if their treating physician has opted for single-agent immunotherapy: pembrolizumab, atezolizumab, or cemiplimab-rwlc. Participants with non-squamous and squamous subtype, predictive biomarker PD-L1 ≥50%, and the treating clinician has opted for combination chemo/immunotherapy OR participants with non-squamous and squamous subtype, predictive biomarker PD-L1 1-49% or unknown: Participants will receive one of the following--pembrolizumab, atezolizumab, or cemiplimab-rwlc--and ALSO receive: * Carboplatin OR * Cisplatin PLUS * Pemetrexed (non-squamous subtype only) OR * Paclitaxel (squamous subtype only) OR * Nab-paclitaxel (squamous subtype only)

Drug: Pembrolizumab; Drug: Atezolizumab; Drug: Cemiplimab-Rwlc; Drug: Carboplatin; Drug: Paclitaxel; Drug: Nab paclitaxel; Drug: Pemetrexed; Drug: Cisplatin; Other: Quality of Life Questionnaire, lung cancer-specific (QLQ-LC13); Other: QLQ-C30 Global Health/Quality of Life Questionnaire; Other: COPD Assessment Test and modified Medical Research Council Dyspnea Patient Reported Outcomes; Other: PROMIS and FACT-G Questionnaires; Other: Sleep Disorder Assessments (ISI, Berlin Sleep Questionnaire)

Interventions

Nab paclitaxel DRUG

FOR PARTICIPANTS IN EITHER ARM with squamous subtype, predictive biomarker PD-L1 ≥50%, and the treating clinician has opted for combination chemo/immunotherapy OR squamous subtype, predictive biomarker PD-L1 1-49% or unknown: Nab-paclitaxel 100 mg/m2 on day 1, 8, 15 of 3-week cycle for 4 cycles.

Performance Status 0-1 Participants; Performance Status 2 Participants

Pemetrexed DRUG

FOR PARTICIPANTS IN EITHER ARM with non-squamous subtype, predictive biomarker PD-L1 ≥50%, and the treating clinician has opted for combination chemo/immunotherapy OR non-squamous subtype, predictive biomarker PD-L1 1-49% or unknown: Pemetrexed 500 mg/m2 IV on day 1 of each 3-week cycle for 4 cycles.

Performance Status 0-1 Participants; Performance Status 2 Participants

Pembrolizumab DRUG

ALL PARTICIPANTS: Pembrolizumab 200 mg intravenously (IV) on day 1 of each 3-week cycle for 4 cycles.

Performance Status 0-1 Participants; Performance Status 2 Participants

Carboplatin DRUG

FOR PARTICIPANTS IN EITHER ARM with non-squamous or squamous subtype, predictive biomarker PD-L1 ≥50%, and the treating clinician has opted for combination chemo/immunotherapy OR non-squamous or squamous subtype, predictive biomarker PD-L1 1-49% or unknown: Carboplatin area under the curve (AUC) 5 IV on day 1 of each 3-week cycle for 4 cycles. AUC dosing (5-6) will be selected by the treating provider.

Performance Status 0-1 Participants; Performance Status 2 Participants

Paclitaxel DRUG

FOR PARTICIPANTS IN EITHER ARM with squamous subtype, predictive biomarker PD-L1 ≥50%, and the treating clinician has opted for combination chemo/immunotherapy OR squamous subtype, predictive biomarker PD-L1 1-49% or unknown: Paclitaxel 200 mg/m2 IV on day 1 of each 3-week cycle for 4 cycles.

Performance Status 0-1 Participants; Performance Status 2 Participants

Atezolizumab DRUG

ALL PARTICIPANTS: 1,200 mg IV on day 1 over 60 minutes of each 3-week cycle for 4 cycles. If the first infusion is tolerated, then all subsequent infusions (cycles 2-4) may be delivered over 30 minutes. The subcutaneous formulation of atezolizumab may be substituted for the intravenous formulation as follows: Atezolizumab hyaluronidase-tqjs 15 mL (1,875 mg atezolizumab and 30,000 units hyaluronidase) subcutaneously into the thigh over 7 minutes on day 1 of each 3-week cycle for 4 cycles.

Performance Status 0-1 Participants; Performance Status 2 Participants

Cemiplimab-Rwlc DRUG

ALL PARTICIPANTS: 350 mg IV over 30 minutes on day 1 of each 3-week cycle for 4 cycles.

Performance Status 0-1 Participants; Performance Status 2 Participants

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

Performance Status 0-1 Participants; Performance Status 2 Participants

Cisplatin DRUG

FOR PARTICIPANTS IN EITHER ARM with non-squamous or squamous subtype, predictive biomarker PD-L1 ≥50%, and the treating clinician has opted for combination chemo/immunotherapy OR non-squamous or squamous subtype, predictive biomarker PD-L1 1-49% or unknown: Cisplatin 75 mg/m2 IV on day 1 of each 3-week cycle for 4 cycles.

Performance Status 0-1 Participants; Performance Status 2 Participants

QLQ-C30 Global Health/Quality of Life Questionnaire 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.

Performance Status 0-1 Participants; Performance Status 2 Participants

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

Performance Status 0-1 Participants; Performance Status 2 Participants

PROMIS and FACT-G Questionnaires OTHER

PROMIS 4-item short forms: Fatigue, Sleep Disturbance, Anxiety, and Depression as well as 1 item from the FACT-G which has been established as a valid indicator of treatment side effect bother ("I am bothered by side effects of treatment"); 17 symptom burden questions in total.

Performance Status 0-1 Participants; Performance Status 2 Participants

Sleep Disorder Assessments (ISI, Berlin Sleep Questionnaire) OTHER

7 items on the Insomnia Severity Index (ISI) and 10 items from the Berlin Sleep Questionnaire, a risk assessment for obstructive sleep apnea.

Performance Status 0-1 Participants; Performance Status 2 Participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• Wake Forest University Health Sciences: lead

Study Sites (2)

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

RECRUITING

Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; atezolizumab; Carboplatin; Paclitaxel; Taxes; Pemetrexed; Cisplatin

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)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; 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; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Thomas Lycan, Jr., D.O., M.H.S.

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Project Manager

CONTACT

336-716-5772; Melani.Terry@advocatehealth.org

Study Design

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

Study Record Dates

• First Submitted: January 31, 2020
• First Posted: February 5, 2020
• Study Start: July 1, 2020
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: September 25, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)