Pilot Study of Performance Status 2 vs. Performance Status 0-1 Non-small Cell Lung Cancer Patients Treated With Chemo/Immunotherapy
Phase 2
Recruiting
- Conditions
- Nonsmall Cell Lung CancerPerformance Status
- Interventions
- Other: Quality of Life Questionnaire, lung cancer-specific (QLQ-LC13)Other: QLQ-C30 Global Health/Quality of Life QuestionnaireOther: COPD Assessment Test and modified Medical Research Council Dyspnea Patient Reported Outcomes
- Registration Number
- NCT04253964
- Lead Sponsor
- Wake Forest University Health Sciences
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 80
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 radiographically measurable metastatic disease by RECIST criteria.
- 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).
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Performance Status 2 Participants QLQ-C30 Global Health/Quality of Life Questionnaire 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 Performance Status 0-1 Participants Quality of Life Questionnaire, lung cancer-specific (QLQ-LC13) 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 Performance Status 0-1 Participants QLQ-C30 Global Health/Quality of Life Questionnaire 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 Performance Status 2 Participants Quality of Life Questionnaire, lung cancer-specific (QLQ-LC13) 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 Performance Status 0-1 Participants COPD Assessment Test and modified Medical Research Council Dyspnea Patient Reported Outcomes 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 Performance Status 2 Participants Nab paclitaxel 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 Performance Status 0-1 Participants Nab paclitaxel 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 Performance Status 2 Participants COPD Assessment Test and modified Medical Research Council Dyspnea Patient Reported Outcomes 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 Performance Status 0-1 Participants Pembrolizumab 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 Performance Status 0-1 Participants Paclitaxel 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 Performance Status 0-1 Participants Carboplatin 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 Performance Status 0-1 Participants Pemetrexed 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 Performance Status 2 Participants Paclitaxel 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 Performance Status 2 Participants Pembrolizumab 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 Performance Status 2 Participants Carboplatin 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 Performance Status 2 Participants Pemetrexed 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
- Primary Outcome Measures
Name Time Method Proportion of Participants with Progression-Free Survival From baseline to end of 4th cycle of treatment (12 weeks) Using non-blinded central imaging using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 to define progressive disease.
- Secondary Outcome Measures
Name Time Method Change in Overall Quality of Life/Global Health Status - EORTC QLQ-C30 From baseline to end of 4th cycle of treatment (12 weeks) 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.
Proportion of Participants with Deterioration in Symptoms - QLQ-LC13 From baseline to end of 4th cycle of treatment (12 weeks) 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)
Incidences of Grade 3 to Grade 5 Treatment-Related Adverse Events 12 weeks Adverse events will be defined using CTCAE Version 5.0 after four cycles (12 weeks).
Trial Locations
- Locations (1)
Wake Forest Baptist Comprehensive Cancer Center
🇺🇸Winston-Salem, North Carolina, United States