NCT03830918

Niraparib, Temozolomide and Atezolizumab in Treating Patients With Advanced Solid Tumors and Extensive-Stage Small Cell Lung Cancer With a Complete or Partial Response to Platinum-Based First-Line Chemotherapy

An Open-Label Phase 1b Dose-Finding Trial Evaluating the Safety of Niraparib and Temozolomide and Atezolizumab in Participants With Advanced Solid Tumors and Expansion to a Phase 2 Trial Comparing the Effects of Niraparib and Temozolomide Plus Atezolizumab vs. Atezolizumab as Maintenance Therapy in Participants With Extensive-Stage Small Cell Lung Cancer With a Complete or Partial Response to Platinum-Based First-Line Chemotherapy (TRIO-US L-06)

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 59 (actual)
• Sponsor: Jonsson Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase Ib/II trial studies the best dose of temozolomide and how well it works with niraparib and atezolizumab in treating patients with solid tumors that have spread to other places in the body (advanced) and extensive-stage small cell lung cancer with a complete or partial response to platinum-based first-line chemotherapy. 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. Niraparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving temozolomide, niraparib and atezolizumab may work better in treating patients with advanced solid tumors and extensive-stage small cell lung cancer.

Detailed description

PRIMARY OBJECTIVES: I. Determine the recommended phase II dose (RP2D) of temozolomide in combination with niraparib and atezolizumab. (Phase Ib) II. Evaluate the efficacy of niraparib plus temozolomide plus atezolizumab at RP2D (Arm A) compared with atezolizumab (Arm B) as measured by progression-free survival (PFS). (Phase II) SECONDARY OBJECTIVES: I. To evaluate the efficacy of niraparib plus temozolomide plus atezolizumab compared with atezolizumab alone, as measured by overall survival (OS). II. To evaluate the efficacy of niraparib plus temozolomide plus atezolizumab compared with atezolizumab alone, as measured by objective response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. III. To evaluate the safety of niraparib plus temozolomide plus atezolizumab compared with atezolizumab alone as measured by adverse events (AEs). EXPLORATORY OBJECTIVE: I. To assess participant-reported outcomes on health-related quality of life and adverse events. OUTLINE: This is a dose-escalation study of temozolomide. Patients are randomized to 1 of 2 arms. ARM A: Patients receive temozolomide orally (PO) once daily (QD) on days 1-5 and niraparib PO QD on days 1-28. Cycles repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care atezolizumab intravenously (IV) every 3 weeks in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive standard of care atezolizumab IV every 3 weeks 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 24 weeks, and then every 12 weeks for up to 1 year.

Conditions

• Advanced Malignant Solid Neoplasm
• Extensive Stage Lung Small Cell Carcinoma
• Stage III Lung Cancer AJCC v8
• Stage IIIA Lung Cancer AJCC v8
• Stage IIIB Lung Cancer AJCC v8
• Stage IIIC Lung Cancer AJCC v8
• Stage IV Lung Cancer AJCC v8
• Stage IVA Lung Cancer AJCC v8
• Stage IVB Lung Cancer AJCC v8

Interventions

Type	Name	Description
BIOLOGICAL	Atezolizumab	Given IV
DRUG	Niraparib	Given PO
OTHER	Quality-of-Life Assessment	Ancillary studies
OTHER	Questionnaire Administration	Ancillary studies
DRUG	Temozolomide	Given PO

Timeline

• Start date: 2019-03-06
• Primary completion: 2027-01-03
• Completion: 2027-01-03
• First posted: 2019-02-05
• Last updated: 2026-02-12

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study