Clinical Trials /

Subsequent Line Gemcitabine and Nivolumab in Treating Participants With Metastatic Small Cell Lung Cancer

NCT03662074

Description:

This phase II pilot trial studies how well gemcitabine and nivolumab work in treating participants with small cell lung cancer that has spread to other parts of the body after other treatments have failed. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Giving second-line gemcitabine and nivolumab may work better in treating participants with small cell lung cancer.

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Second Line Gemcitabine and Nivolumab in Treating Participants With Metastatic Small Cell Lung Cancer
  • Official Title: Phase II Pilot Study of 2nd Line Gemcitabine and Nivolumab for Advanced SCLC

Clinical Trial IDs

  • ORG STUDY ID: IRB00051024
  • SECONDARY ID: NCI-2018-01803
  • SECONDARY ID: CCCWFU 62418
  • SECONDARY ID: P30CA012197
  • NCT ID: NCT03662074

Conditions

  • Small Cell Lung Carcinoma
  • Stage IV Lung Cancer AJCC v8
  • Stage IVA Lung Cancer AJCC v8
  • Stage IVB Lung Cancer AJCC v8

Interventions

DrugSynonymsArms
GemcitabinedFdC, dFdCyd, DifluorodeoxycytidineTreatment (gemcitabine, nivolumab)
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoTreatment (gemcitabine, nivolumab)

Purpose

This phase II pilot trial studies how well gemcitabine and nivolumab work in treating participants with small cell lung cancer that has spread to other parts of the body after other treatments have failed. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Giving second-line gemcitabine and nivolumab may work better in treating participants with small cell lung cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To compare response rate (RR) of gemcitabine and nivolumab (G+N) after 4 cycles (8 weeks)
      to historical controls treated with nivolumab alone.

      SECONDARY OBJECTIVES:

      I. To compare median overall survival (OS) of G+N to historical controls treated with
      nivolumab alone.

      II. To compare median progression-free survival (PFS) of G+N to historical controls treated
      with nivolumab alone.

      III. To evaluate for tolerability of G+N at each treatment cycle and then every 8 weeks after
      treatment is completed.

      EXPLORATORY OBJECTIVES:

      I. To correlate immunophenotypic changes among lymphocytes (quantitative measurements of CD4
      and CD8 T-cells) with radiographic response and overall survival before treatment, after
      treatment and between 8-12 weeks after treatment.

      II. Among those patients with tumor mutation burden (TMB) status available, to describe the
      association between TMB (low, medium, or high) and RR, OS, and PFS.

      III. Assess the patient perspective of symptomatic adverse events using self-reported items
      from the National Cancer Institute (NCI) Patient Reported Outcomes-Common Terminology
      Criteria for Adverse Events (PRO-CTCAE).

      OUTLINE:

      Participants receive gemcitabine intravenously (IV) over 30 minutes and nivolumab IV over 60
      minutes on day 1. Treatment repeats every 2 weeks for up to 4 courses in the absence of
      disease progression or unacceptable toxicity.

      After completion of study treatment, participants are followed up at 30 days, 6-10 weeks, and
      every 8 weeks thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (gemcitabine, nivolumab)ExperimentalParticipants receive gemcitabine IV over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity
  • Gemcitabine
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed incurable SCLC and have
             had prior treatment with platinum-based chemotherapy.

          -  Patients should not be demonstrating end-organ damage due to rapid progression of
             disease based on the most recent assessment of the treating physician.

          -  Patients must have radiographically measurable metastatic disease by Response
             Evaluation Criteria in Solid Tumors (RECIST) criteria.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

          -  Absolute neutrophil count >= 1,500/mcL.

          -  Platelets >= 100,000/mcL.

          -  Chemotherapy agents are known to be teratogenic, therefore women of child-bearing
             potential and men must agree to use adequate contraception (hormonal or barrier method
             of birth control) prior to study entry and for the duration of study participation.
             Should a woman become pregnant or suspect she is pregnant while participating in this
             study, she should inform her treating physician immediately.

          -  Ability to understand and the willingness to sign an Institutional Review Board
             (IRB)-approved informed consent document.

        Exclusion Criteria:

          -  Previously received gemcitabine or nivolumab. Patients who have previously received
             other types of immune checkpoint inhibitors (besides nivolumab) can be enrolled.

          -  Emergent need for palliative radiation.

          -  Patients may not be receiving any other investigational agents for the treatment of
             NSCLC.

          -  History of allergic reaction to gemcitabine.

          -  Uncontrolled intercurrent illness including, but not limited to ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Pregnant women are excluded from this study because of the potential for teratogenic
             or abortifacient effects with chemotherapy. Because there is an unknown but potential
             risk for adverse events in nursing infants secondary to treatment of the mother with
             chemotherapy, breastfeeding should be discontinued.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Radiographic response rate (RR) per Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame:Up to 8 weeks
Safety Issue:
Description:Objective RR (complete response [CR] + partial response [PR]) will be compared between this study sample and a historical benchmark value of 10%. For this comparison we will use a one-sample test of proportion.

Secondary Outcome Measures

Measure:Overall survival (OS)
Time Frame:Duration of time from the start of treatment to date of death, assessed up to 2 years
Safety Issue:
Description:OS will be estimated using standard Kaplan Meier survival analysis methods.
Measure:Progression-free survival (PFS)
Time Frame:Duration of time from the start of treatment to the time of investigator assessed progression or death, assessed up to 2 years
Safety Issue:
Description:PFS will be estimated using standard Kaplan Meier survival analysis methods.
Measure:Incidence of adverse events per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time Frame:Up to 2 years
Safety Issue:
Description:Toxicity rates will be estimated by responder status and presented overall and by body site.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Wake Forest University Health Sciences

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