Nivolumab and Temozolomide in Treating Patients With Recurrent or Refractory Small-Cell Lung Cancer or Advanced Neuroendocrine Cancer
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|ClinicalTrials.gov Identifier: NCT03728361|
Recruitment Status : Recruiting
First Posted : November 2, 2018
Last Update Posted : November 6, 2019
|Condition or disease||Intervention/treatment||Phase|
|Grade I Neuroendocrine Carcinoma Grade II Neuroendocrine Carcinoma Grade III Neuroendocrine Carcinoma Metastatic Neuroendocrine Carcinoma Neuroendocrine Carcinoma Recurrent Small Cell Lung Carcinoma Refractory Small Cell Lung Carcinoma Lung Cancer Stage IV Large Cell Neuroendocrine Carcinoma Neuroendocrine Tumors Small Cell Lung Cancer Metastatic Small-cell Lung Cancer||Biological: Nivolumab Drug: Temozolomide||Phase 2|
I. To evaluate the efficacy (using response rate per RECIST v1.1) of nivolumab and temozolomide for the treatment of patients with either small cell lung cancer that have progressed or recurred after prior platinum-based chemotherapy and immunotherapy (cohort 1), or progressive metastatic neuroendocrine carcinoma of any grade or primary site in any line of therapy (cohort 2).
I. To evaluate the safety profile and toxicity of combination nivolumab and temozolomide as per Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0.
II. To evaluate the progression free survival (PFS) and overall survival (OS) of patients treated with combination nivolumab and temozolomide.
III. To evaluate the central nervous system (CNS) PFS of patients with small cell lung cancer (SCLC) treated with nivolumab and temozolomide.
I. To determine whether treatment with nivolumab and temozolomide leads to a decrease in immune-suppressive cell populations (ie myeloid-derived suppressor cells [MDSC]) in peripheral blood.
II. To determine whether objective response rate (ORR), PFS, OS vary by tumor O6-methylguanine deoxyribonucleic acid (DNA) methyltransferase (MGMT) methylation at baseline.
III. To determine whether baseline tumor mutational burden is predictive of response to therapy in patients with SCLC treated with nivolumab and temozolomide.
IV. To determine whether changes in blood based mutation burden during treatment may predict clinical benefit.
V. To determine whether a composite immune and tumor cell staining score can be developed with or without PD-L1 by immunohistochemistry (IHC) to predict response in the SCLC cohort.
Patients receive nivolumab intravenously (IV) on day 1 of a 28 day cycle. Patients also receive temozolomide orally (PO) on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, every 8 weeks for 12 months, then every 12 weeks thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||53 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II, Multi-Cohort Trial of Combination Nivolumab and Temozolomide in Recurrent/Refractory Small-Cell Lung Cancer and Advanced Neuroendocrine Tumors|
|Actual Study Start Date :||December 31, 2018|
|Estimated Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||December 31, 2021|
Experimental: Treatment (nivolumab, temozolomide)
Patients receive nivolumab IV on day 1 of a 28 day cycle. Patients also receive temozolomide PO on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Objective response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria [ Time Frame: Up to 3 years ]Response will be defined by a complete response (CR) or partial response (PR), confirmed or unconfirmed. Response will be defined for patients with measurable disease and who receive at least one dose of combination treatment. Exact binomial 95% confidence intervals for the true PR+CR response rate will be calculated.
- Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [ Time Frame: Up to 3 years ]Attribution to drug, time-of-onset, duration of the event, resolution, and any concomitant medications administered will be recorded. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either ?unrelated? or ?unlikely to be related? to study treatment in the event of an actual relationship developing.
- Progression-free survival (PFS) [ Time Frame: The time from allocation to the first documented disease progression according to RECIST 1.1 or death due to any cause, whichever occurs first, assessed up to 3 years ]The Kaplan-Meier method will be used.
- Central nervous system (CNS) PFS [ Time Frame: The time from allocation to the first documented disease progression within the CNS according to RECIST 1.1, assessed up to 3 years ]CNS PFS will be measured for patients with relapsed vs refractory small-cell lung cancer (SCLC) in cohort 1. The Kaplan-Meier method will be used.
- Overall survival (OS) of patients [ Time Frame: Up to 3 years ]The Kaplan-Meier method will be used.
- Exploratory Biomarker analysis [ Time Frame: Up to 3 years ]The study will evaluate PD-L1 by immunohistochemistry (IHC), and assess the clinical outcomes (ie OS) between patients with high expression and low expression of PD-L1.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03728361
|Contact: Ohio State Comprehensive Cancer Center||1-800-293-5066||OSUCCCClinicaltrials@osumc.edu|
|Contact: Carly Pilcherfirstname.lastname@example.org|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Carly Pilcher 614-366-6174 email@example.com|
|Principal Investigator: Dwight H. Owen, MD, MS|
|Principal Investigator:||Dwight Owen, MD, MS||Ohio State University Comprehensive Cancer Center|