Combination Rucaparib With Nivolumab in Small Cell Lung Carcinoma

Study Overview
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Brief Summary
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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
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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).

Official Title
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Phase II Study of Combination Rucaparib With Nivolumab in Platinum-Sensitive Small Cell Lung Carcinoma Patients as Maintenance After Induction Therapy With Platinum Doublet

Conditions
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Small Cell Lung Cancer

Intervention / Treatment
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* Combination Product: Rucaparib and Nivolumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with Stage IV SCLC<br>Patients with extensive stage (IV) SCLC (small cell lung cancer) | Combination Product: Rucaparib and Nivolumab<br>* Rucaparib (600mg BID) and Nivolumab (480mg IV q4 wk)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Duration (time) of progression-free survival after response to initial platinum-based therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions from starting maintenance treatment | 0-2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate | Disease control rate (DCR) is the number of patients who had either complete response (CR, Disappearance of all target lesions), partial response (PR, >=30% decrease in the sum of the longest diameter of target lesions) or stable disease (SD, less than 30% decrease in the sum of the biggest dimension but no more than 20% increase ) per RECICST 1.0 divided by the total number of patients. DOR= (CR+PR+SD)/Total number on trial x 100%. The timepoints were combined. The best responses were used in calculating disease control rate | 8 weeks, 16 weeks and 24 weeks post-treatment | 
| Overall Survival | Percentage of surviving participants at 1 and 2 years | 0-2 years | 
| Objective Response Rate | 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. The timepoints were combined. The best responses were used in calculating objective response rate | 8 weeks, 16 weeks and 24 weeks post-treatment | 
| Quality of Life Scale Baseline | 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. | Baseline | 
| Quality of Life Scale 4 Months | 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. | 4 months | 
| Quality of Life Scale at Disease Progression | 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. | Disease Progression up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rucaparib, nivolumab, platinum-sensitive, maintenance, SCLC, immune checkpoint, PARP