Clinical Trials /

Combination Rucaparib With Nivolumab in Small Cell Lung Carcinoma

NCT03958045

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.

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

  • Small Cell Lung Cancer

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

NameTypeDescriptionInterventions
Patients with Stage IV SCLCExperimentalPatients 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