Combination Rucaparib With Nivolumab in Small Cell Lung Carcinoma
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|ClinicalTrials.gov Identifier: NCT03958045|
Recruitment Status : Not yet recruiting
First Posted : May 21, 2019
Last Update Posted : May 21, 2019
|Condition or disease||Intervention/treatment||Phase|
|Small Cell Lung Cancer||Combination Product: Rucaparib and Nivolumab||Phase 2|
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).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Estimated Study Start Date :||July 2019|
|Estimated Primary Completion Date :||July 2023|
|Estimated Study Completion Date :||July 2024|
Experimental: Patients with Stage IV SCLC
Patients with extensive stage (IV) SCLC (small cell lung cancer)
Combination Product: Rucaparib and Nivolumab
Rucaparib (600mg BID) and Nivolumab (480mg IV q4 wk)
- Progression Free Survival [ Time Frame: 0-3 years ]Duration (time) of progression-free survival after response to initial platinum-based therapy.
- Disease Control Rate [ Time Frame: 8 weeks, 16 weeks and 24 weeks post-treatment ]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.
- Overall Survival [ Time Frame: 0-2 years ]The time from first dose of trial medication to date of death due to any cause.
- Objective Response Rate [ Time Frame: 8 weeks, 16 weeks and 24 weeks post-treatment ]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.
- Quality of Life Scale [ Time Frame: 0-2 years ]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.
- Tumor Mutation Burden [ Time Frame: 0-3 years ]Correlate tumor mutation burden with treatment response.
- PD-L1 CPS [ Time Frame: 0-3 years ]A combined positive score (CPS) for Programmed Death Ligand 1 (PD-L1) will be derived from immunohistochemical analysis of tumor tissue.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03958045
|Contact: Aman Chauhan, MDfirstname.lastname@example.org|
|United States, Kentucky|
|Markey Cancer Center, University of Kentucky||Not yet recruiting|
|Lexington, Kentucky, United States, 40536|
|Contact: Aman Chauhan, MD 859-257-7715 email@example.com|
|Principal Investigator:||Aman Chauhan, MD||University of Kentucky|