Clinical Trials /

Combination of Interferon-gamma and Nivolumab for Advanced Solid Tumors

NCT02614456

Description:

This is a phase I study of combination immunotherapy with IFN-γ and the PD-1 inhibitor nivolumab in patients with advanced solid tumors who have progressed on at least one prior systemic therapy, which may include prior immunotherapy.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Combination of Interferon-gamma and Nivolumab for Advanced Solid Tumors
  • Official Title: Combination Immunotherapy With Interferon-gamma and Nivolumab for Patients With Advanced Solid Tumors: A Phase 1 Study

Clinical Trial IDs

  • ORG STUDY ID: GU-084
  • NCT ID: NCT02614456

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
interferon-gamma and nivolumabInterferon-gamma and nivolumab

Purpose

This is a phase I study of combination immunotherapy with IFN-γ and the PD-1 inhibitor nivolumab in patients with advanced solid tumors who have progressed on at least one prior systemic therapy, which may include prior immunotherapy.

Detailed Description

      This is a phase I study of combination immunotherapy with IFN-γ and the PD-1 inhibitor
      nivolumab in patients with advanced solid tumors who have progressed on at least one prior
      systemic therapy, which may include prior immunotherapy. Patients will be treated with a one
      week induction phase (IP) of IFN-γ, followed by a combination phase (CP) with IFN-γ and
      nivolumab for three cycles, followed by a single agent phase of only nivolumab for up to one
      year. The study will primarily assess the safety and tolerability of the combination. Tumor
      assessments will occur after three cycles of combination therapy, then every three cycles
      thereafter. Secondary objectives including ORR, PFS, and OS will also be assessed, as will
      various correlative analyses. Initial accrual will occur using a modified 6+6 design, and if
      endpoints for safety (using DLT criteria) are met, expansion cohorts in RCC and UC will be
      opened for up to 15 patients.
    

Trial Arms

NameTypeDescriptionInterventions
Interferon-gamma and nivolumabExperimentalInterferon-gamma (IFN-γ): starting dose 50 mcg/m2 subcutaneously Nivolumab: 3 mg/kg intravenously Induction phase: IFN-γ every other day alone for 1 week Combination phase: IFN-γ every other day & Nivolumab every 2 weeks for 3 months Single agent phase: Nivolumab every 3 weeks up to 1 year
  • interferon-gamma and nivolumab

Eligibility Criteria

        Inclusion Criteria:

          1. Patients must have a histologically or cytologically confirmed metastatic solid tumor
             that has shown clinical or pre-clinical evidence of responding to anti-PD-1 therapy or
             the capacity to up-regulate PD-L1. These tumor types may include but may not be
             limited to: RCC, UC, melanoma, non small cell lung cancer (NSCLC), small cell lung
             cancer, squamous cell cancer of the head and neck (SCCHN), ovarian carcinoma, triple
             negative breast cancer, gastric cancer, microsatellite instability expressing
             (MSI-high) colon cancer, hepatocellular carcinoma, mesothelioma, gastrointestinal
             stromal tumors, endometrial carcinoma, liposarcomas, chondrosarcomas, and uterine
             sarcomas. Patients with solid tumor types not listed above may be enrolled at the
             discretion of the Principal Investigator.

             Note: Dose expansion phase will include two cohorts and consist of patients with
             either metastatic UC or RCC, but must meet all other inclusion criteria.

          2. All patients must have received at least one line of systemic therapy in the
             metastatic setting. Prior immunotherapy is allowed, including prior treatment with
             nivolumab or another PD-1 inhibitor, as long as the reason for discontinuation of a
             prior PD-1 inhibitor was not for drug-related toxicity.

          3. Patients must have measurable disease per RECIST criteria v. 1.1 as described in
             detail in section 11.0.

          4. Patients must have a site of disease that is amenable to pretreatment and on-treatment
             core biopies. At least 3 formalin fixed, paraffin embedded (FFPE) slides at five
             microns each may be collected at each biopsy. Determination of tissue accessibility
             and quantity will be made by the consenting clinician. Patients must consent to the
             two study-required biopsy procedures.

          5. Age > 18 years.

          6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

          7. Patients must have normal organ and marrow function as defined below:

               -  Absolute neutrophil count > 1,500/mcL

               -  Platelets > 100,000/mcL

               -  Total bilirubin < 1.5 times the upper limit of normal (ULN), except patients with
                  Gilbert's syndrome in whom total bilirubin must be <3.0 mg/dL

               -  AST/ALT (SGOT/SGPT) < 3 times institutional normal limits

               -  Creatinine < 1.5 times the ULN OR Creatinine clearance > 40 mL/min (as measured
                  or calculated by Cockroft-Gault formula)

          8. Ability to understand and willingness to sign a written informed consent and HIPAA
             consent document.

        Exclusion Criteria:

          1. Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering
             the study.

          2. Patients may not have any active or recent history of a known or suspected autoimmune
             disease or recent history of a syndrome that required systemic corticosteroids or
             immunosuppressive medications, except for syndromes which would not be expected to
             recur in the absence of an external trigger. Subjects with vitiligo, type I diabetes
             mellitus, or residual hypothyroidism due to autoimmune thyroiditis only requiring
             hormone replacement are permitted to enroll.

          3. Any condition requiring systemic treatment with corticosteroids (> 10 mg daily
             prednisone or equivalent) or other immunosuppressive medications within 14 days prior
             to first dose of study drug. Inhaled or topical steroids and adrenal replacement
             steroid doses > 10 mg daily prednisone or equivalent are permitted in the absence of
             active autoimmune disease.

          4. Patients may not be receiving any other investigational agents.

          5. Patients with known active or symptomatic central nervous system (CNS) metastases
             and/or carcinomatous meningitis. Asymptomatic, treated, and/or stable brain
             metastases, as measured by subsequent radiologic evaluations at least two months
             apart, are permitted.

          6. History of allergic reactions attributed to compound of similar chemical or biologic
             composition to the agent(s) used in this study.

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

          8. Known human immunodeficiency virus (HIV) positive or history of acquired immune
             deficiency syndrome (AIDS) or AIDS-defining illness.

          9. Known current or a history of hepatitis B or C virus, including chronic and dormant
             states, unless disease has been treated and confirmed cleared.

         10. Any medical condition that in the investigator's opinion could interfere with
             interpretation of study or toxicity, or increase the risk to the patient related to
             potential toxicity.

         11. Major surgery within 4 weeks of initiation of study drug.

         12. Pregnant or breast feeding. Refer to section 4.4 for further detail.

         13. A second invasive malignancy requiring active treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with treatment-related adverse events as assesses by CTCAE version 4.03.
Time Frame:58 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:To evaluate the investigator assessed ORR using standard response evaluation criteria in solid tumors (RECIST) version 1.1 for metastatic renal cell carcinoma.
Time Frame:2 years
Safety Issue:
Description:
Measure:To evaluate the investigator assessed ORR using standard response evaluation criteria in solid tumors (RECIST) version 1.1 for metastatic urothelial cancer.
Time Frame:2 years
Safety Issue:
Description:
Measure:To evaluate median progression free survival (PFS) using Kaplan-Meier curves for metastatic renal cell carcinoma.
Time Frame:2 years
Safety Issue:
Description:
Measure:To evaluate median progression free survival (PFS) using Kaplan-Meier curves for metastatic urothelial cancer.
Time Frame:2 years
Safety Issue:
Description:
Measure:To evaluate median overall survival (OS) using Kaplan-Meier curves for metastatic renal cell carcinoma.
Time Frame:2 years
Safety Issue:
Description:
Measure:To evaluate median overall survival (OS) using Kaplan-Meier curves for metastatic urothelial cancer.
Time Frame:2 years
Safety Issue:
Description:
Measure:To investigate the relationship between PD-L1 expression on tumor cells and on immune cells using IHC and SMI methods.
Time Frame:Baseline
Safety Issue:
Description:
Measure:To investigate the relationship between PD-L1 expression on tumor cells and on immune cells using IHC and SMI methods.
Time Frame:week 2
Safety Issue:
Description:
Measure:To investigate the relationship between PD-L1 expression on tumor cells and on immune cells using IHC and SMI methods.
Time Frame:week 7
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Fox Chase Cancer Center

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