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Combination Rucaparib With Nivolumab in Small Cell Lung Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03958045
Recruitment Status : Recruiting
First Posted : May 21, 2019
Last Update Posted : August 16, 2021
Clovis Oncology, Inc.
Information provided by (Responsible Party):
Aman Chauhan, University of Kentucky

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.

Condition or disease Intervention/treatment Phase
Small Cell Lung Cancer Combination Product: Rucaparib and Nivolumab Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 4, 2019
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : July 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
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)

Primary Outcome Measures :
  1. Progression Free Survival [ Time Frame: 0-3 years ]
    Duration (time) of progression-free survival after response to initial platinum-based therapy.

Secondary Outcome Measures :
  1. 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.

  2. Overall Survival [ Time Frame: 0-2 years ]
    The time from first dose of trial medication to date of death due to any cause.

  3. 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.

  4. 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.

Other Outcome Measures:
  1. Tumor Mutation Burden [ Time Frame: 0-3 years ]
    Correlate tumor mutation burden with treatment response.

  2. 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03958045

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Contact: Aman Chauhan, MD 859-257-7715

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United States, Kentucky
Markey Cancer Center, University of Kentucky Recruiting
Lexington, Kentucky, United States, 40536
Contact: Aman Chauhan, MD    859-257-7715   
Sponsors and Collaborators
Aman Chauhan
Clovis Oncology, Inc.
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Principal Investigator: Aman Chauhan, MD University of Kentucky
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Responsible Party: Aman Chauhan, Professor, University of Kentucky Identifier: NCT03958045    
Other Study ID Numbers: 49346 MCC-18-LUN-107-CLO
First Posted: May 21, 2019    Key Record Dates
Last Update Posted: August 16, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Aman Chauhan, University of Kentucky:
immune checkpoint
Additional relevant MeSH terms:
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Small Cell Lung Carcinoma
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors