Clinical Trials /

Ipilimumab and Nivolumab in Recurrent Extensive Stage Small Cell Lung Cancer After Receiving Platinum-based Chemotherapy

NCT03670056

Description:

This is a pilot study of patients who previously received platinum chemotherapy with recurrent SCLC to evaluate the change in the ratio of intratumoral Teff/Treg cells and clinical benefit of treatment with nivolumab and ipilimumab.

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Suspended

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Pilot Study of Combination Immunotherapy With Ipilimumab and Nivolumab in Patients With Recurrent Extensive Stage Small Cell Lung Cancer (SCLC) Who Have Previously Received Platinum-based Chemotherapy
  • Official Title: A Pilot Study of Combination Immunotherapy With Ipilimumab and Nivolumab in Patients With Recurrent Extensive Stage Small Cell Lung Cancer (SCLC) Who Have Previously Received Platinum-based Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: 2000023361
  • SECONDARY ID: CA209-9YT
  • NCT ID: NCT03670056

Conditions

  • Small Cell Lung Cancer

Interventions

DrugSynonymsArms
Combination immunotherapy with Ipilimumab and NivolumabNivolumab and Ipilumumab

Purpose

This is a pilot study of patients who previously received platinum chemotherapy with recurrent SCLC to evaluate the change in the ratio of intratumoral Teff/Treg cells and clinical benefit of treatment with nivolumab and ipilumumab.

Detailed Description

      The primary objective of this study is t assess whether the change in the ratio of effector T
      cells (Teff) to regulatory T cells (Treg), i.e. CD8 positive/FoxP3 expressing CD4 T cells,
      between pre- and on- treatment biopsies, will predict clinical response in patients with
      recurrent SCLC treated with combination therapy with nivolumab and ipilimumab.

      Secondary bbjectives of the study include: to determine the objective response rate per
      RECIST 1.1 and immune-related response criteria, duration of response, progression free
      survival, and overall survival with nivolumab and ipilimumab in patients with recurrent SCLC;
      to evaluate changes in the tumor immune microenvironment and blood after treatment with
      ipilimumab and nivolumab; and to evaluate circulating tumor DNA (ctDNA) as a marker for
      response to therapy.
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab and IpilumumabExperimentalPatients will be treated with nivolumab 1 mg/kg and ipilimumab 3 mg/kg, starting on Day 1. Patients will receive 4 doses of each nivolumab and ipilimumab and then will receive nivolumab 240 mg starting week 13 (day 85) every 2 weeks until progression, unacceptable toxicity, withdrawal of consent, or the study ends, whichever occurs first.
  • Combination immunotherapy with Ipilimumab and Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically documented ES-SCLC with documented disease progression
             after at least one prior systemic regimen, including one platinum-based regimen.

          -  Patients previously diagnosed with limited stage SCLC treated with concurrent
             chemoradiation with a platinum doublet now diagnosed with recurrent extensive disease
             are eligible.

          -  ECOG performance status of 0 to 2

          -  Measurable disease with at least one tumor site amenable to biopsy

          -  Patients may have untreated asymptomatic CNS metastases or treated CNS metastases if
             they are not currently receiving corticosteroids greater than dexamethasone 2 mg daily
             or equivalent for 7 days prior to the first dose of study drug. - Patients should have
             completed stereotactic radiation or whole-brain radiation at least 2 weeks prior to
             Cycle 1, Day 1.

        Exclusion Criteria:

          -  Patients with an active autoimmune disease requiring systemic treatment within the
             past 3 months or a documented history of clinically severe autoimmune disease, or a
             syndrome that requires systemic steroids > dexamethasone 2 mg daily (or equivalent
             dose of other corticosteroids) or other immunosuppressive agents.

          -  Treatment with systemic immunosuppressive medications including but not limited to,
             dexamethasone at doses > 2 mg or equivalent dose of other corticosteroids,
             cyclophosphamide, tacrolimus, sirolimus, azathioprine, methotrexate, thalidomide, and
             antitumor necrosis factor (anti-TNF) agents within 2 weeks prior to initiation of
             trial therapy. Inhaled or topically applied steroids, and acute and chronic
             standard-dose NSAIDs are permitted. Replacement steroids are also permitted.

          -  Prior treatment with anti-PD1, anti-PDL1 or anti-CTLA4 antibodies.

          -  Symptomatic untreated CNS metastases. Patients with asymptomatic CNS metastases are
             eligible. Patients with symptomatic brain metastases are eligible, provided they meet
             all of the following criteria:

               -  Completed stereotactic radiosurgery or whole- brain radiation at least 2 weeks
                  prior to Cycle 1, Day 1.

               -  No evidence of interim progression between the completion of CNS-directed therapy
                  and the start of trial therapy.

               -  No ongoing requirement for steroids greater than dexamethasone 2 mg daily (or
                  equivalent dose of other corticosteroids) as therapy for CNS disease;
                  anticonvulsants at a stable dose are allowed.

          -  History of leptomeningeal carcinomatosis.

          -  Interstitial lung disease that is symptomatic or may interfere with the detection or
             management of suspected drug-related pulmonary toxicity.

          -  Any systemic anti-cancer chemotherapy, within 21 days prior to initiation of study
             treatment.

          -  Treatment with any other investigational agent or participation in another clinical
             trial with therapeutic intent within 21 days prior to enrollment.

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

          -  Major surgery or traumatic injury within 4 weeks of starting study drug.

          -  Women who are pregnant or lactating.

          -  Known infection with HIV, HBV or HCV. Patients with prior exposure to hepatitis, but
             no evidence of active or chronic infection, may be eligible.

          -  Evidence of end-organ damage as defined by the following laboratory results obtained
             within 14 days prior to the first study treatment:

               -  ANC <1,000 cells/μL (without granulocyte colony-stimulating factor support within
                  2 weeks prior to Cycle 1, Day 1).

               -  Platelet count <75,000/μL (without transfusion within 2 weeks prior to Cycle 1,
                  Day 1).

               -  Hemoglobin <8.0 g/dL (Patients may be transfused to meet this criterion).

               -  AST and ALT ≥2.5 x ULN, with the following exceptions: Patients with documented
                  liver metastases: AST and/or ALT≥5 x ULN.

               -  Serum bilirubin ≥1.5 x ULN (Patients with known Gilbert disease who have serum
                  bilirubin level ≥3 x ULN may be enrolled).

               -  INR and aPTT ≥1.5 x ULN (This applies only to patients who are not receiving
                  therapeutic anticoagulation; patients receiving therapeutic anticoagulation
                  should be on a stable dose).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in the ratio of Teff/Treg cells
Time Frame:Up to 12 months
Safety Issue:
Description:The primary analysis will use the nonparametric Mann-Whitney sign test to compare the change in the ratio of Teff/Treg cells in those patients who respond or not to treatment. This test compares the rate of response in those with above and below Teff/Treg ratio.

Secondary Outcome Measures

Measure:Response rate
Time Frame:Up to 12 months
Safety Issue:
Description:Objective response is defined as a complete or partial response, as determined by investigator assessment using RECIST v1.1 and immune-related response criteria (irRC) . Response will be confirmed by repeat assessments ≥4 weeks after initial documentation. Patients not meeting these criteria, including patients without any post baseline tumor assessment, will be considered non-responders in the analysis of objective response.
Measure:Duration of response
Time Frame:Up to 12 months
Safety Issue:
Description:Duration of response is defined as the time from the initial complete or partial response to the time of disease progression or death, whichever occurs first. If a patient does not experience death or disease progression before the end of the study, duration of response will be censored at the day of the last tumor assessment. If no tumor assessments were performed after the date of the first occurrence of a complete or partial response, duration of objective response will be censored at the date of the first occurrence of a complete or partial response plus 1 day.
Measure:Progression-free survival
Time Frame:Up to 12 months
Safety Issue:
Description:Progression-free survival (PFS) is defined as the time from the first day of treatment until progression of disease using RECIST v1.1 and immune-related response criteria (irRC) . If a patient has not experienced progressive disease or death, PFS will be censored at the day of the last tumor assessment. Patients with no post baseline tumor assessments will be censored at the date of first study treatment plus 1 day.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Yale University

Trial Keywords

  • combination immunotherapy
  • platinum-based chemotherapy

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