A Single Arm Trial of Adjuvant Pembrolizumab in Patients With Limited Stage Small Cell Lung Cancer
Overview
- Phase
- Phase 2
- Intervention
- Cisplatin
- Conditions
- Limited Stage Lung Small Cell Carcinoma
- Sponsor
- Vanderbilt-Ingram Cancer Center
- Enrollment
- 1
- Locations
- 1
- Primary Endpoint
- Progression-free survival
- Status
- Terminated
- Last Updated
- 11 months ago
Overview
Brief Summary
This phase II trial studies how well pembrolizumab after standard treatment with radiation plus the following chemotherapy drugs: cisplatin or carboplatin, plus etoposide works in treating patients with limited stage small cell lung cancer (LS-SCLC). 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 pembrolizumab after standard treatment with radiation plus chemotherapy may increase the ability of the immune system to fight LS-SCLC.
Detailed Description
PRIMARY OBJECTIVE: I. To investigate progression free survival per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) as assessed by the investigator in patients with limited stage small cell lung cancer treated with adjuvant pembrolizumab. SECONDARY OBJECTIVES: I. Assess median overall survival compared to the historical control dataset (CONVERT trial1) median overall survival (OS) of 30 months. II. Assess the safety and tolerability of adjuvant pembrolizumab in patients with limited stage SCLC. EXPLORATORY/TRANSLATIONAL OBJECTIVES: I. To determine whether patients with detectable circulating tumor deoxyribonucleic acid (ctDNA) after curative intent therapy ("minimal residual disease \[MRD\] positive") experience shorter median progression free survival (PFS) compared to patients without detectable ctDNA after curative intent therapy ("MRD negative."). II. Determination of whether patients with ctDNA clearance at any point during curative intent therapy have superior median PFS compared to patients who do not experience ctDNA clearance during curative intent therapy. OUTLINE: Patients undergo radiation therapy and receive cisplatin or carboplatin on day 1 of each cycle and etoposide on days 1-3 for 4 cycles. Patients then receive pembrolizumab intravenously (IV) over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo positron emission tomography (PET) scan during screening. Patients also undergo magnetic resonance imaging (MRI) throughout the trial as well as computed tomography (CT). Additionally, patients undergo blood sample collection throughout the trial. After completion of study treatment, patients are followed up at 30 days, and every 12 weeks for 2 years.
Investigators
Ryan Whitaker
Assistant Professor of Medicine
Vanderbilt-Ingram Cancer Center
Eligibility Criteria
Inclusion Criteria
- •Has LS-SCLC (stage I-III, by American Joint Committee on Cancer \[AJCC\] 8th Edition Cancer Staging) and no evidence of extensive stage disease. Participants may enroll at any time between diagnosis and initiation of definitive concurrent chemoradiation or surgery followed by adjuvant chemotherapy. Correlative analyses collected during standard of care definitive concurrent chemoradiation or surgery followed by adjuvant chemotherapy are mandatory
- •Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of small cell lung cancer or high grade neuroendocrine carcinoma will be enrolled in this study
- •Contraception requirements should conform with Clinical Trials Facilitation and Coordination Group (CTFG) guidelines. The pembrolizumab standard for use of highly effective contraceptive methods for persons of child-bearing potential (POCBP) is 120 days (5 half-lives) after the last dose. Please either list the contraception requirement for each compound in the study or use the longest time frame that covers requirements for all compounds in the study
- •Similarly, Company standard for abstaining from breastfeeding after study intervention is at least 5 half-lives. For pembrolizumab, this is 120 days
- •No radiological imaging evidence of disease progression after completion of definitive concurrent chemoradiation or surgery followed by adjuvant chemotherapy
- •The participant (or legally acceptable representative if applicable) provides written informed consent for the trial
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention
- •Participants who are hepatitis B surface antibody (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) anti-viral therapy for at least 4 weeks, and have undetectable HBV viral load prior to randomization.
- •Note: Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.
Exclusion Criteria
- •Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137)
- •Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to allocation
- •Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities requiring corticosteroids, and not have had radiation pneumonitis. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study drug
- •Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed
- •Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab
- •Has a known additional malignancy that is progressing or requires active treatment. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, localized prostate adenocarcinoma, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. Participants with low-risk early-stage prostate cancer (T1-T2a, Gleason score =\< 6, and prostate-specific antigen \[PSA\]\< 10 ng/mL) untreated in active surveillance with stable disease are not excluded
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has severe hypersensitivity (≥ grade 3) to pembrolizumab
- •Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed
Arms & Interventions
Treatment (pembrolizumab)
Patients undergo radiation therapy and receive cisplatin or carboplatin on day 1 of each cycle and etoposide on days 1-3 for 4 cycles. Patients then receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo PET scan during screening. Patients also undergo MRI throughout the trial as well as CT. Additionally, patients undergo blood sample collection throughout the trial.
Intervention: Cisplatin
Treatment (pembrolizumab)
Patients undergo radiation therapy and receive cisplatin or carboplatin on day 1 of each cycle and etoposide on days 1-3 for 4 cycles. Patients then receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo PET scan during screening. Patients also undergo MRI throughout the trial as well as CT. Additionally, patients undergo blood sample collection throughout the trial.
Intervention: Carboplatin
Treatment (pembrolizumab)
Patients undergo radiation therapy and receive cisplatin or carboplatin on day 1 of each cycle and etoposide on days 1-3 for 4 cycles. Patients then receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo PET scan during screening. Patients also undergo MRI throughout the trial as well as CT. Additionally, patients undergo blood sample collection throughout the trial.
Intervention: Etoposide
Treatment (pembrolizumab)
Patients undergo radiation therapy and receive cisplatin or carboplatin on day 1 of each cycle and etoposide on days 1-3 for 4 cycles. Patients then receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo PET scan during screening. Patients also undergo MRI throughout the trial as well as CT. Additionally, patients undergo blood sample collection throughout the trial.
Intervention: Pembrolizumab
Treatment (pembrolizumab)
Patients undergo radiation therapy and receive cisplatin or carboplatin on day 1 of each cycle and etoposide on days 1-3 for 4 cycles. Patients then receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo PET scan during screening. Patients also undergo MRI throughout the trial as well as CT. Additionally, patients undergo blood sample collection throughout the trial.
Intervention: Computed Tomography
Treatment (pembrolizumab)
Patients undergo radiation therapy and receive cisplatin or carboplatin on day 1 of each cycle and etoposide on days 1-3 for 4 cycles. Patients then receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo PET scan during screening. Patients also undergo MRI throughout the trial as well as CT. Additionally, patients undergo blood sample collection throughout the trial.
Intervention: Positron Emission Tomography
Treatment (pembrolizumab)
Patients undergo radiation therapy and receive cisplatin or carboplatin on day 1 of each cycle and etoposide on days 1-3 for 4 cycles. Patients then receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo PET scan during screening. Patients also undergo MRI throughout the trial as well as CT. Additionally, patients undergo blood sample collection throughout the trial.
Intervention: Magnetic Resonance Imaging
Treatment (pembrolizumab)
Patients undergo radiation therapy and receive cisplatin or carboplatin on day 1 of each cycle and etoposide on days 1-3 for 4 cycles. Patients then receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo PET scan during screening. Patients also undergo MRI throughout the trial as well as CT. Additionally, patients undergo blood sample collection throughout the trial.
Intervention: Biospecimen Collection
Treatment (pembrolizumab)
Patients undergo radiation therapy and receive cisplatin or carboplatin on day 1 of each cycle and etoposide on days 1-3 for 4 cycles. Patients then receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo PET scan during screening. Patients also undergo MRI throughout the trial as well as CT. Additionally, patients undergo blood sample collection throughout the trial.
Intervention: Radiation Therapy
Outcomes
Primary Outcomes
Progression-free survival
Time Frame: Time from the date of first treatment to progressive disease or death due to any cause, whichever occurs first, assessed up to 3 years
Secondary Outcomes
- Overall survival(Time from the date of first treatment to the date of death due to any cause, assessed up to 3 years)
- Incidence of adverse events(Up to 3 years)