Clinical trial NCT06731413: Reduced CT + Anti-PD-1 as First Line Tx in Vulnerable Older Adults w/Adv <50% PD-L1 Non-Small Cell Lung Cancer (NSCLC)
Official title: Phase 2 Study to Evaluate Reduced Dose Chemotherapy in Combination With Anti-PD-1 Therapy as First Line Treatment in Vulnerable or Older Adults (Vulnerable or Age ≥70) With Advanced PD-L1 TPS <50% Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
NSCLC
Advanced Non-Small Cell Lung Cancer
Metastatic Non Small Cell Lung Cancer
Keywords: Non-Small Cell Lung Cancer, NSCLC
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
First posted: 2024-12-12
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) (either squamous or non- squamous)
* Stage 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
* 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

Primary outcomes:
measure: Occurrence of chemotherapy discontinuation due to treatment-related adverse events
timeFrame: Through completion of protocol therapy, up to 2 years
Secondary outcomes:
measure: Response (complete response and partial response) per Response Evaluation Criteria in Solid Tumors
timeFrame: Up to 5 years
measure: Overall incidence and severity of all adverse events assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
timeFrame: 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
measure: 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
timeFrame: Up to 5 years
measure: Progression-free survival (PFS) measured from the date of first study treatment until the date of documented disease progression
timeFrame: Up to 5 years
measure: Cancer related symptoms and quality of life
timeFrame: Baseline, Cycle 3 Day 1, Cycle 5 Day 1 Cycle 9 Day 1, EOT Visit (up to 2 years)
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Jonathan Berkman, MD
role: PRINCIPAL_INVESTIGATOR
References: