Description:
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.
Title
- Brief Title: Combination Rucaparib With Nivolumab in Small Cell Lung Carcinoma
- Official Title: Phase II Study of Combination Rucaparib With Nivolumab in Platinum-Sensitive Small Cell Lung Carcinoma Patients as Maintenance After Induction Therapy With Platinum Doublet
Clinical Trial IDs
- ORG STUDY ID:
49346 MCC-18-LUN-107-CLO
- NCT ID:
NCT03958045
Conditions
Purpose
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 3
years).
Trial Arms
Name | Type | Description | Interventions |
---|
Patients with Stage IV SCLC | Experimental | Patients with extensive stage (IV) SCLC (small cell lung cancer) | |
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Progression Free Survival |
Time Frame: | 0-3 years |
Safety Issue: | |
Description: | Duration (time) of progression-free survival after response to initial platinum-based therapy. |
Secondary Outcome Measures
Measure: | Disease Control Rate |
Time Frame: | 8 weeks, 16 weeks and 24 weeks post-treatment |
Safety Issue: | |
Description: | Disease control rate is the percentage of subjects who had a partial response post-initial chemotherapy and who have a confirmed reduction in tumor size compared to post-induction chemotherapy baseline or fulfilling the criteria for stable disease. |
Measure: | Overall Survival |
Time Frame: | 0-2 years |
Safety Issue: | |
Description: | The time from first dose of trial medication to date of death due to any cause. |
Measure: | Objective Response Rate |
Time Frame: | 8 weeks, 16 weeks and 24 weeks post-treatment |
Safety Issue: | |
Description: | Objective response rate (ORR) is the proportion of patients with complete response or partial response according to RECIST v1.1. Patients with complete response at baseline will be excluded from ORR analysis. |
Measure: | Quality of Life Scale |
Time Frame: | 0-2 years |
Safety Issue: | |
Description: | Quality of life is assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questionnaire, which probes function and symptoms. Scores range from 0-100. High scores on functional scales represent a high/healthy level of functioning; high scores symptom scales represent a high level of symptomology. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Aman Chauhan |
Trial Keywords
- rucaparib
- nivolumab
- platinum-sensitive
- maintenance
- SCLC
- immune checkpoint
- PARP
Last Updated
August 16, 2021