Combination Rucaparib With Nivolumab in Small Cell Lung Carcinoma

NCT ID: NCT03958045

Last Updated: 2024-10-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-04
• Study Completion Date: 2022-11-15

Brief Summary

The purpose of this study is to evaluate survival and response rate of the combination rucaparib and nivolumab as maintenance therapy in platinum-sensitive small cell lung carcinoma.

Detailed Description

Small cell lung cancer (SCLC) is one of the most aggressive malignancies with a 5-year survival rate of less than 7%. SCLC is characterized by rapid doubling time, high growth fraction and early development of widespread metastases. SCLC accounts for roughly 93% of all high-grade neuroendocrine carcinomas. The prognosis for SCLC is extremely poor with a median survival less than a year for extensive-stage disease. Therapeutic options have not advanced significantly in over two decades, with frontline treatment consisting of platinum doublet therapy for 3-6 cycles. While most patients show an initial favorable response to Carboplatin/cisplatin + etoposide, this response is usually short-lived. Most patients relapse with resistant disease between 3 to 6 months after completion of initial chemotherapy.

Based on preclinical data supporting the role of immune checkpoint and PARP (poly ADP ribose polymerase ) inhibitors in SCLC, combining nivolumab and rucaparib has the potential to prolong progression-free survival and overall survival. These two classes of drugs have non-overlapping toxicities. This novel combination has not been tried in a front-line maintenance setting for SCLC.

Eligible patients will have pathological (biopsy) or cytologically confirmed stage IV SCLC, and have achieved either partial or complete response post frontline chemotherapy with platinum doublet. Patients will be treated with combination rucaparib and nivolumab. The recommended starting dose of rucaparib as a continuously administered oral monotherapy is 600 mg BID. Nivolumab will be administered as an intravenous infusion once every 4 weeks at a fixed dose of 480 mg. In the absence of treatment delays due to adverse event(s), treatment may continue for 24 months.

Progression-free survival, overall survival, disease control rates, objective response rate, quality of life, and tumor mutation burden will be evaluated during this study (up to 2 years).

Conditions

Small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Patients with Stage IV SCLC

Patients with extensive stage (IV) SCLC (small cell lung cancer)

Group Type: EXPERIMENTAL

Rucaparib and Nivolumab

Intervention Type: COMBINATION_PRODUCT

Rucaparib (600mg BID) and Nivolumab (480mg IV q4 wk)

Interventions

Rucaparib and Nivolumab

Rucaparib (600mg BID) and Nivolumab (480mg IV q4 wk)

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

Inclusion Criteria

• Patients with histologically or cytologically confirmed stage IV, extensive stage, small cell lung cancer who achieved either partial or complete remission per RECIST 1.1 post frontline chemotherapy with platinum doublet (Cisplatin or Carboplatin/etoposide).
• Enrollment is within 6 weeks of last (4th cycle) of chemotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Adequate Bone Marrow Function
• Adequate Hepatic Function

Exclusion Criteria

• Prior therapy with any antibody/drug targeting T-cell co-regulatory proteins (immune checkpoints)
• Major surgery within 4 weeks of initiation of study medication.
• Current use of (some) immunosuppressants
• Active infection requiring systemic therapy
• HIV/AIDS
• Hepatitis B virus or hepatitis C virus infection at screening
• Autoimmune disease
• Persisting toxicity related to prior therapy
• Pregnancy
• Vaccination (except inactive) within 4 weeks of the first dose of nivolumab
• Hypersensitivity to the study drugs
• Cardiovascular disease
• Untreated central nervous system (CNS) metastases or leptomeningeal carcinomatosis
• (Some) active secondary malignancy
• Active pneumonitis or interstitial lung disease

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clovis Oncology, Inc.

INDUSTRY

Sponsor Role: collaborator

Zhonglin Hao

OTHER

Sponsor Role: lead

Responsible Party

Zhonglin Hao

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Zhonglin Hao, MD

Role: PRINCIPAL_INVESTIGATOR

University of Kentucky

Locations

Markey Cancer Center, University of Kentucky

Lexington, Kentucky, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

49346 MCC-18-LUN-107-CLO

Identifier Type: -

Identifier Source: org_study_id