Advanced Non-Small Cell Lung Cancer, Metastatic Non Small Cell Lung Cancer, Non-Small Cell Lung Cancer, NSCLC
Conditions
Keywords
Non-Small Cell Lung Cancer, NSCLC
Brief summary
Evaluate frequency of adverse events that lead to chemotherapy discontinuation in vulnerable older adults with recurrent/metastatic PD-L1 TPS\<50% NSCLC patients who receive reduced dose chemotherapy in combination with immunotherapy.
Detailed description
This is a single institution, single arm, open label phase 2 study in vulnerable or older adults (Age ≥70) with recurrent or metastatic, histologically confirmed squamous cell carcinoma or non-squamous cell carcinoma of lung without driver mutation and PD-L1 TPS \< 50% to evaluate safety and tolerability of reduced dose of chemotherapy and immunotherapy.
Interventions
DRUGReduced Dose of Chemotherapy and Immunotherapy
Eligible participants with recurrent or metastatic squamous cell carcinoma will receive 4 cycles of carboplatin area under the curve (AUC) 3 IV every 21 days and paclitaxel 135 mg/m2 intravenous (IV) every 21 days. Participants with non-squamous histology will receive carboplatin AUC 3 IV every 21 days and pemetrexed 375 mg/m2 IV every 21 days (collectively, induction chemotherapy). Both groups will receive pembrolizumab 200 mg IV every 21 days for a total of up to 35 cycles (Cycles ≥5 are collectively the maintenance portion of treatment) or until disease progression or unacceptable toxicity.
Sponsors
Virginia Commonwealth University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) (either squamous or non- squamous) * Stage IIIB, IIIC or IV disease OR have recurrent disease and not be candidates for curative treatment such as combined chemo-radiation * No previous line of treatment in the recurrent or metastatic setting. Neoadjuvant or adjuvant treatment more than 6 months before enrollment is acceptable. * Age 70 or meeting frailty definition or above at the date of signing informed consent * Absence of driver mutations that have first line Food and Drug Administration (FDA) approved targeted therapy (biomarker testing is optional for squamous cell) * PD-L1 tumor proportion score (TPS) of less than 50% * Eastern Cooperative Oncology Group (ECOG) PS of 0-3 * Have measurable disease based on RECIST 1.1 as determined by the local site investigator/radiology assessment * Absolute neutrophil count (ANC) ≥ 1,000/μL * Platelets ≥ 75,000/μL * Hemoglobin (Hgb) ≥ 8.0 g/dL (transfusion permitted) * Total bilirubin ≤ 2 x institutional upper limit of normal (ULN) * Aspartate amino transferase (AST)serum glutamic-oxaloacetic transaminase (SGOT) /alanine aminotransferase (ALT)serum glutamic-pyruvic transaminase (SGPT) ≤ 5.0 × institutional ULN * Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* Participants with life expectancy of less than 3 months at the time of enrollment * Has active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, or immunosuppressive drugs) * Diagnosis of interstitial lung disease * Creatinine clearance of \<30 mL/min * Symptomatic, untreated central nervous system (CNS) disease or leptomeningeal disease. Patients with asymptomatic or treated CNS disease are eligible * Required ongoing use of immunosuppressive medication, including steroids, with the following allowable exceptions: * Doses less than or equal to the equivalent of prednisone 10 mg daily * Short courses of steroids that are discontinued prior to enrollment * Inhaled, intranasal and/or topical steroids * Dexamethasone taper for treating vasogenic edema associated with CNS disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of chemotherapy discontinuation due to treatment-related adverse events | Through completion of protocol therapy, up to 2 years | Evaluate treatment tolerability i by the number of participants that discontinue chemotherapy treatment due to treatment-related adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response (complete response and partial response) per Response Evaluation Criteria in Solid Tumors | Up to 5 years | Evaluate overall response defined by complete and partial response in vulnerable or older adults with recurrent/metastatic PD-L1 TPS \<50% NSCLC patients who receive reduced dose chemotherapy in combination with immunotherapy per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 |
| Overall incidence and severity of all adverse events assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 | Time of patient consent and throughout the duration of the study, including during the treatment period and for 30 days following the final dose of the study medication, up to 2 years and 1 month | The total number of AE's recorded for the protocol. |
| Overall survival defined as the time from the date of first study treatment until the date of death. Overall survival (OS) will be censored on the last date a participant was known to be alive | Up to 5 years | Overall survival of participants measured in days. |
| Progression-free survival (PFS) measured from the date of first study treatment until the date of documented disease progression | Up to 5 years | Evaluate progression-free survival of participants in days utilizing RECIST 1.1 criteria or death from any cause, whichever occurs first. |
| Cancer related symptoms and quality of life | Baseline, Cycle 3 Day 1, Cycle 5 Day 1 Cycle 9 Day 1, EOT Visit (up to 2 years) | Evaluate impact of the reduced dose combination therapy on quality of life as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-QLQ C30). The EORTC QLG Core Questionnaire (EORTC QLQ-C30) is a 30 item instrument meant to assess some of the different aspects that define the quality of life of cancer patients.The functioning and the global QoL scales, a higher score indicates better health. Response options are on a 4-point Likert-type scale (not at all; a little; quite a bit; very much) and a 7-point Likert scale for global HRQoL ranging from 'Very poor' to 'Excellent'. The QLQ-C30 summary score is calculated as the mean of the combined 13 QLQ-C30 scale and item scores with a higher score indicating a better HRQoL. |
Countries
United States
Contacts
CONTACTMassey IIT Research Operations
PRINCIPAL_INVESTIGATORJonathan Berkman, MD
Virginia Commonwealth University
Outcome results
None listed