Reduced Dose Chemotherapy in Combination with Immunotherapy for the Treatment of Stage IV Non-small Cell Lung Cancer in Vulnerable or Older Adults with a PD-L1 Tumor Proportion Score < 50%

Status: active

This phase II trial studies whether a lower dose (reduced dose) of chemotherapy combined with immunotherapy has fewer side effects and to see how well it works in treating stage IV non-small cell lung cancer (NSCLC) in patients with physical limitations (vulnerable) or that are >=70 (older) and have a PD-L1 tumor proportion score (TPS) < 50%. Lung cancer is a leading cause of cancer-related deaths worldwide. It is often diagnosed in older adults. Older adults are often not included in clinical trials, which means it is not fully understood how usual treatments work or how safe they are for older adults. Standard chemotherapy for NSCLC includes paclitaxel or pemetrexed and carboplatin. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make deoxyribonucleic acid (DNA) and may kill tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving reduced dose chemotherapy with immunotherapy may have fewer side effects and/or may be effective in treating vulnerable or older adults with advanced or recurrent PD-L1 TPS < 50% NSCLC.

Inclusion Criteria

Histologically or cytologically confirmed diagnosis of 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 lines of treatment in the recurrent or metastatic setting. Neoadjuvant or adjuvant treatment more than 6 months before enrollment is acceptable. Prior chemoradiation for stage III with recurrence is allowed
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 TPS of less than 50%
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-3
Have measurable disease based on Response Evaluation Criteria in Solid Tumors (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 aminotransferase (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 OBJECTIVE:

I. Evaluate treatment tolerability in vulnerable or older adults with recurrent/metastatic PD-L1 TPS < 50% NSCLC patients who receive reduced dose chemotherapy in combination with immunotherapy.

SECONDARY OBJECTIVES:

I. Evaluate the frequency and severity of all adverse events of reduced dose chemotherapy in combination with immunotherapy in vulnerable or older adults with recurrent/metastatic PD-L1 TPS < 50% NSCLC patients who receive reduced dose chemotherapy in combination with immunotherapy.

II. Estimate overall survival (OS) in vulnerable or older adults with recurrent/metastatic PD-L1 TPS < 50% NSCLC who receive reduced dose chemotherapy in combination with immunotherapy.

III. Valuate overall response defined by complete and PR in vulnerable or older adults with recurrent/metastatic PD-L1 TPS < 50% NSCLC patients who receive reduced dose chemotherapy in combination with immunotherapy.

IV. Evaluate progression free survival of in vulnerable or older adults with recurrent/metastatic PD-L1 TPS < 50% NSCLC patients who receive reduced dose chemotherapy in combination with immunotherapy.

V. Evaluate impact of the reduced dose combination therapy on quality of life.

OUTLINE: Patients are assigned to 1 of 2 groups.

GROUP I (SQUAMOUS HISTOLOGY): Patients receive paclitaxel intravenously (IV), carboplatin IV, and pembrolizumab IV over 25-40 minutes on day 1 of cycles 1-4. Beginning cycle 5, patients receive pembrolizumab IV over 25-40 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and computed tomography (CT) or positron emission tomography (PET) throughout the study. Patients may also undergo magnetic resonance imaging (MRI) during screening.

GROUP II (NON-SQUAMOUS HISTOLOGY): Patients receive pemetrexed IV over 10 minutes, carboplatin IV, and pembrolizumab IV over 25-40 minutes on day 1 of cycles 1-4. Beginning cycle 5, patients receive pembrolizumab IV over 25-40 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and CT or PET throughout the study. Patients may also undergo MRI during screening.

After completion of study treatment, patients are followed up for 5 years from the date of enrollment.

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Reduced Dose Chemotherapy in Combination with Immunotherapy for the Treatment of Stage IV Non-small Cell Lung Cancer in Vulnerable or Older Adults with a PD-L1 Tumor Proportion Score < 50%

Inclusion Criteria

Exclusion Criteria

United States

Virginia

Richmond

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Reduced Dose Chemotherapy in Combination with Immunotherapy for the Treatment of Stage IV Non-small Cell Lung Cancer in Vulnerable or Older Adults with a PD-L1 Tumor Proportion Score < 50%

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