Clinical Trials /

Rucaparib and Pembrolizumab for Maintenance Therapy in Stage IV Non-Squamous Non-Small Cell Lung Cancer

NCT03559049

Description:

This study is a multi-center, Phase I/II, single arm trial to assess the safety and efficacy of the combination of oral rucaparib plus intravenous pembrolizumab as maintenance therapy in patients with stage IV non-squamous non-small cell lung cancer (NSCLC) without progressive disease (PD), as confirmed on CT scans, after induction therapy with carboplatin/pemetrexed/pembrolizumab (CPP) triplet therapy.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Rucaparib and Pembrolizumab for Maintenance Therapy in Stage IV Non-Squamous Non-Small Cell Lung Cancer
  • Official Title: A Phase I/II Multi-site Study of Rucaparib and Pembrolizumab Maintenance Therapy in Stage IV Non-Squamous Non-Small Cell Lung Cancer After Initial Therapy With Carboplatin, Pemetrexed, and Pembrolizumab

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2018.033
  • SECONDARY ID: HUM00142973
  • NCT ID: NCT03559049

Conditions

  • Stage IV Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
PembrolizumabRucaparib and Pembrolizumab Maintenance
PemetrexedRucaparib and Pembrolizumab Maintenance
CarboplatinRucaparib and Pembrolizumab Maintenance
RucaparibRucaparib and Pembrolizumab Maintenance

Purpose

This study is a multi-center, Phase I/II, single arm trial to assess the safety and efficacy of the combination of oral rucaparib plus intravenous pembrolizumab as maintenance therapy in patients with stage IV non-squamous non-small cell lung cancer (NSCLC) without progressive disease (PD), as confirmed on CT scans, after induction therapy with carboplatin/pemetrexed/pembrolizumab (CPP) triplet therapy.

Trial Arms

NameTypeDescriptionInterventions
Rucaparib and Pembrolizumab MaintenanceExperimentalAll patients will receive induction therapy with Pembrolizumab (200mg IV on day 1 of every 21 days), Pemetrexed (500mg/m^2 IV on day 1 of every 21 days), and Carboplatin (AUC5 IV on day 1 of every 21 days). This will be followed by maintenance therapy with Pembrolizumab (200mg IV on day 1 of every 21 days) and Rucaparib (600mg PO BID days 1-21 of each 21 day cycle).
  • Pembrolizumab
  • Pemetrexed
  • Carboplatin
  • Rucaparib

Eligibility Criteria

        Inclusion Criteria:

          -  Have a life expectancy of at least 3 months

          -  Have a histologically confirmed diagnosis of stage IV non-squamous NSCLC (non-small
             cell lung cancer) whose tumors do not have an epidermal sensitizing growth factor
             (EGFR) mutation or BRAF mutation or rearrangements in ALK (anaplastic lymphoma kinase)
             or ROS-1 and have at least one measurable lesion based on RECIST v1.1

          -  Have a performance status of 0 or 1 on the ECOG Performance Scale (Eastern Cooperative
             Oncology Group scoring system used to quantify general well-being and activities of
             daily life; scores range from 0 to 5 where 0 represents perfect health and 5
             represents death)

          -  Demonstrate adequate organ function

          -  Female subjects of childbearing potential should have a serum pregnancy within 14 days
             of enrollment and 72 hours prior to receiving the first dose of study medications.

          -  Female subjects of childbearing potential must be willing to use a highly effective
             method of contraception for the course of the study through 180 days after the last
             dose of study medications.

          -  Male subjects of childbearing potential must agree to use an adequate method of
             contraception starting with the first dose of study therapy through 180 days after the
             last dose of study therapy.

          -  Adequate tissue sample for correlative studies

        Exclusion Criteria:

          -  Received previous systemic therapy for stage IV NSCLC

          -  Received radiation to the lungs >30Gy ≤6 months of enrollment

          -  Received palliative radiation within 7 days of enrollment

          -  Had prior treatment with any other anti-PD-1, PD-L1, or PD-L2 agent or an antibody
             targeting other immune-regulatory receptors or mechanisms

          -  Received prior treatment with a PARP inhibitor

          -  Has a known history of prior malignancy except if the patient has undergone
             potentially curative therapy with no evidence of that disease recurrence for 5 years
             since initiation of that therapy

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis

          -  Has active autoimmune disease that has required systemic treatment within the past 2
             years

          -  Subjects requiring daily corticosteroids >10mg of prednisone (or its equivalent) would
             be excluded from the study.

          -  Has evidence of interstitial lung disease or a history of non-infectious pneumonitis
             that required oral or intravenous glucocorticoids to assist with management

          -  Has an active infection requiring systemic therapy

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with informed consent through 180 days after
             the last dose of trial treatment

          -  Has a diagnosis of immunodeficiency (including Human Immunodeficiency Virus (HIV) or
             acquired immunodeficiency (AIDS)-related illness) or is receiving systemic steroid
             therapy or any other form of immunosuppressive therapy within 7 days prior to
             enrollment

          -  Has a known history of active TB (Bacillus Tuberculosis)

          -  Has known active Hepatitis B or Hepatitis C

          -  Has received a live vaccine within 30 days of enrollment

          -  A medical condition that requires daily systemic corticosteroids, greater than the
             equivalent of 10mg of prednisone
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Median duration of time from start of treatment to time of progression
Time Frame:Up to 5 years
Safety Issue:
Description:The primary endpoint is median progression free survival (PFS) which is defined as the median duration of time from the start of treatment to progression. Progression is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions.

Secondary Outcome Measures

Measure:Median duration of time from the start of treatment until death
Time Frame:Up to 5 years
Safety Issue:
Description:The secondary endpoint is median overall survival (OS) which is defined as the median duration of time from the start of treatment until death.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Michigan Cancer Center

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