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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Nonsmall Cell Lung Cancer; Performance Status
• Intervention / Treatment: Other: Quality of Life Questionnaire, lung cancer-specific (QLQ-LC13); Drug: Pembrolizumab; Drug: Atezolizumab; Drug: Cemiplimab-Rwlc; Drug: Carboplatin; Drug: Paclitaxel; Drug: Nab paclitaxel; Drug: Pemetrexed; Drug: Cisplatin; 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)

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.

• Study Type: Interventional
• Enrollment (Estimated): 105
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Project Manager; Phone Number: 336-716-5772; Email: Melani.Terry@advocatehealth.org

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27105
      • Recruiting
      • Wake Forest Baptist Comprehensive Cancer Center
      • Principal Investigator: Thomas Lycan, Jr., DO, MHS
      • Contact: Project Manager; Phone Number: 336-716-5772; Email: Melani.Terry@advocatehealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Performance Status 0-1 Participants; 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)	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.; Drug: Pembrolizumab; ALL PARTICIPANTS: Pembrolizumab 200 mg intravenously (IV) on day 1 of each 3-week cycle for 4 cycles.; Drug: Atezolizumab; 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.; Drug: Cemiplimab-Rwlc; ALL PARTICIPANTS: 350 mg IV over 30 minutes on day 1 of each 3-week cycle for 4 cycles.; Drug: Carboplatin; 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.; Drug: Paclitaxel; 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.; Drug: Nab paclitaxel; 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.; Drug: Pemetrexed; 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.; Drug: Cisplatin; 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.; 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).; Other: PROMIS and FACT-G Questionnaires; 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.; Other: Sleep Disorder Assessments (ISI, Berlin Sleep Questionnaire); 7 items on the Insomnia Severity Index (ISI) and 10 items from the Berlin Sleep Questionnaire, a risk assessment for obstructive sleep apnea.
Experimental: Performance Status 2 Participants; 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)	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.; Drug: Pembrolizumab; ALL PARTICIPANTS: Pembrolizumab 200 mg intravenously (IV) on day 1 of each 3-week cycle for 4 cycles.; Drug: Atezolizumab; 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.; Drug: Cemiplimab-Rwlc; ALL PARTICIPANTS: 350 mg IV over 30 minutes on day 1 of each 3-week cycle for 4 cycles.; Drug: Carboplatin; 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.; Drug: Paclitaxel; 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.; Drug: Nab paclitaxel; 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.; Drug: Pemetrexed; 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.; Drug: Cisplatin; 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.; 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).; Other: PROMIS and FACT-G Questionnaires; 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.; Other: Sleep Disorder Assessments (ISI, Berlin Sleep Questionnaire); 7 items on the Insomnia Severity Index (ISI) and 10 items from the Berlin Sleep Questionnaire, a risk assessment for obstructive sleep apnea.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidences of Grade 3 to Grade 5 Treatment-Related Adverse Events	Adverse events will be defined using CTCAE Version 5.0 after four cycles (12 weeks).	12 weeks
Change in Overall Quality of Life/Global Health Status - EORTC QLQ-C30	Using the total score of the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), a 30-item questionnaire for 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. Scoring scale : 1 (Not at all) to 4 (Very much), 1 (Very poor) to 7 (Excellent). Minimum score 0, maximum score 100. For functional and global quality of life scales, higher scores mean a better level of functioning. For symptom-oriented scales, a higher score means more severe symptoms.	From baseline to end of 4th cycle of treatment (12 weeks)
Proportion of Participants with Deterioration in Symptoms - QLQ-LC13	Patient reported deterioration in three symptoms: Cough, chest pain, or dyspnea as measured by the symptoms scales as part of the Quality of Life Questionnaire Lung Cancer Module (QLQ-LC13). Deterioration is defined as a 10-point or greater decrease from baseline in either cough, chest pain, or dyspnea and subsequently confirmed by a second adjacent 10-point or greater decrease from baseline in the same symptom)	From baseline to end of 4th cycle of treatment (12 weeks)

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Thomas Lycan, Jr., D.O., M.H.S., Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: January 31, 2020
• First Submitted That Met QC Criteria: January 31, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Actual): August 10, 2026
• Last Update Submitted That Met QC Criteria: August 6, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Diterpenes; Health Care Economics and Organizations; Platinum Compounds; Economics; Pemetrexed; Carboplatin; Paclitaxel; Cisplatin; pembrolizumab; atezolizumab; Taxes
• Other Study ID Numbers: IRB00063540; P30CA012197 (U.S. NIH Grant/Contract); WFBCCC 62619 (Other Identifier: Wake Forest Baptist Comprehensive Cancer Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No