Trials / Active Not Recruiting

Active Not RecruitingNCT03728361

Nivolumab and Temozolomide in Treating Patients With Recurrent or Refractory Small-Cell Lung Cancer or Advanced Neuroendocrine Cancer

A Phase II, Multi-Cohort Trial of Combination Nivolumab and Temozolomide in Recurrent/Refractory Small-Cell Lung Cancer and Advanced Neuroendocrine Tumors

Status: Active Not Recruiting
Phase: Phase 2
Study type: Interventional
Enrollment: 55 (actual)

Sponsor: Dwight Owen · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase II trial studies how well nivolumab and temozolomide work in treating patients with small-cell lung cancer that has come back or does not respond to treatment, or neuroendocrine cancer that has spread to other places in the body. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab and temozolomide may work better in treating patients with small-cell lung cancer and neuroendocrine cancer.

Detailed description

PRIMARY OBJECTIVES: 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). SECONDARY OBJECTIVES: 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. EXPLORATORY OBJECTIVES: 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. OUTLINE: 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.

Conditions

Interventions

Type	Name	Description
BIOLOGICAL	Nivolumab	Given IV
DRUG	Temozolomide	Given PO

Timeline

Start date: 2018-12-31
Primary completion: 2025-12-17
Completion: 2026-10-31
First posted: 2018-11-02
Last updated: 2025-12-18

Locations

2 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT03728361. Inclusion in this directory is not an endorsement.