Clinical Trials /

Nivolumab and Stereotactic Ablative Radiation Therapy (SAbR) for Metastatic Clear Cell Renal Cell Carcinoma

NCT02781506

Description:

Nivolumab (brand name Opdivo): IV, 3 mg/kg q2 weeks, until disease progression or unacceptable toxicity; SABR, dose variable, in 1-3 fractions.

Related Conditions:
  • Clear Cell Renal Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab and Stereotactic Ablative Radiation Therapy (SAbR) for Metastatic Clear Cell Renal Cell Carcinoma
  • Official Title: Phase II Trial of Nivolumab and Stereotactic Ablative Radiation Therapy (SAbR) for Metastatic Clear Cell Renal Cell Carcinoma (mRCC)

Clinical Trial IDs

  • ORG STUDY ID: STU 122015-052
  • NCT ID: NCT02781506

Conditions

  • Metastatic Clear Cell Renal Cell Carcinoma

Interventions

DrugSynonymsArms
NivolumabOpdivoNivolumab and SABR

Purpose

Nivolumab (brand name Opdivo): IV, 3 mg/kg q2 weeks, until disease progression or unacceptable toxicity; SABR, dose variable, in 1-3 fractions.

Detailed Description

      A single institution, safety lead-in phase II trial with SAbR to multiple metastatic sites
      concurrently administered with Nivolumab for patients with metastatic clear cell renal cell
      cancer who have failed at least one anti-angiogenic therapy.
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab and SABRExperimentalNivolumab alone: IV, 3 mg/kg q2 weeks, until disease progression or unacceptable toxicity. SABR, dose variable, in 1-3 fractions.
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  At least 18 years of age

          -  Willing and able to provide consent

          -  Pathologic diagnosis of metastatic RCC with clear cell component

          -  Measurable disease in at least 2 non-radiated sites. Progression or intolerance to at
             least one prior systemic anti-angiogenic therapy.

          -  Eligible for extra-CNS SAbR to 1-6 sites of disease

          -  Must have received at least one prior anti-angiogenic therapy in the advanced or
             metastatic setting. Prior cytokine therapy (eg, IL-2, IFN-α), vaccine therapy, or
             treatment with cytotoxic therapy is also allowed but not any other drug specifically
             targeting T-cell co-stimulation or checkpoint pathways.

          -  Previous treatment with surgery, radiation, chemotherapy, targeted agents (see above)
             are allowed provided that: Chemotherapy/Major surgery was administered > 14 days
             before the start Nivolumab; Minor surgery, radiation, or any targeted agents were
             administered > 7 days before the start of Nivolumab

          -  Performance status ECOG 0, 1, 2 or 3.

          -  Adequate organ and marrow function as defined below (obtained within 14 days of first
             dose of drug):

               -  leukocytes≥ 2,000/mcL

               -  absolute neutrophil count ≥ 1,500/mcL

               -  platelets ≥ 50,000/mcl

               -  total bilirubin ≤ 2mg/dL

               -  AST(SGOT)/ALT(SPGT) ≤ 3 X institutional upper limit of normal

          -  Women of child-bearing potential

               -  female of child-bearing potential is any woman (regardless of sexual orientation,
                  having undergone a tubal ligation, or remaining celibate by choice) who meets the
                  following criteria:

               -  must have a negative serum or urine pregnancy test within 24 hours prior to the
                  start of investigational product.

               -  Women must not be breastfeeding.

               -  must agree to use adequate contraception (hormonal or barrier method of birth
                  control; abstinence) prior to study entry, for the duration of study
                  participation and contraception should be continued for a period of 30 days plus
                  the time required for the investigational drug to undergo five half lives.

               -  Should a woman become pregnant or suspect she is pregnant while participating in
                  this study, she should inform her treating physician immediately.

               -  Men who are sexually active with WOCBP must use any contraceptive method with a
                  failure rate of less than 1% per year. Contraception should be continued for a
                  period of 90 days plus the time required for the investigational drug to undergo
                  five half lives. This is equivalent to 31 weeks after discontinuation of
                  Nivolumab.

          -  Adequate Renal function with Cr ≤ 2.5 mg/dL.

        Exclusion Criteria:

          -  Subjects who have had major surgery (such as nephrectomy) or chemotherapy within 2
             weeks prior to first dose of drug

          -  Subjects who have had radiation therapy within 2 weeks prior to first dose of drug

          -  Uncontrolled adrenal insufficiency or active chronic liver disease

          -  Any history of CNS metastases that is not adequately treated with surgery or SABR >14
             days prior.

          -  Prior treatment with any anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4
             antibody, or any other antibody or drug specifically targeting T-cell co-stimulation
             or checkpoint pathways.

          -  Any positive history for HIV/AIDS, HTLV, hepatitis B or hepatitis C virus indicating
             acute or chronic infection.

          -  Any active known or suspected autoimmune disease. Subjects with vitiligo, type I
             diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring
             hormone replacement, psoriasis not requiring systemic treatment, or conditions not
             expected to recur in the absence of an external trigger are permitted to enroll.

          -  Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily
             prednisone equivalent) or other immunosuppressive medications within 14 days prior to
             the first dose of study drug. Inhaled steroids and adrenal replacement steroid doses
             up to 10 mg daily prednisone equivalent are permitted (although not encouraged) in the
             absence of active autoimmune disease.

          -  Subjects with life expectancy < 6 months

          -  Subjects receiving any other investigational or standard antineoplastic agents.

          -  Prior malignancies active within the previous 3 years except for locally curable
             cancers that have been apparently cured, such as basal or squamous cell skin cancer,
             superficial bladder cancer, or carcinoma in situ of the prostate, cervix, breast?, or
             etc.

          -  Psychiatric illness/social situations that would limit consenting and compliance with
             study requirements.

          -  Patients with history of hypersensitivity to monoclonal antibodies

          -  Subjects who are pregnant or nursing due to the potential for congenital abnormalities
             and the potential of this regimen to harm nursing infants
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response Rate (RR)
Time Frame:5 years
Safety Issue:
Description:The primary objective of the randomized phase II trial will be to increase the RR of treatment with Nivolumab by the concurrent administration of SAbR. The assessment of RR will be based on the evaluation of irRECIST criteria and radiated lesions will be excluded from target lesions.

Secondary Outcome Measures

Measure:Overall survival
Time Frame:5 years
Safety Issue:
Description:To evaluate and compare the overall survival (OS), which is defined as the time between date of registration and the date of death due to any cause, between the Nivolumab alone and the combination therapy arms
Measure:Progression free survival
Time Frame:5 years
Safety Issue:
Description:To evaluate and compare progression free survival (PFS), which is defined as the time between date of registration and the first date of documented disease progression or date of death due to any cause, between the Nivolumab alone and the combination therapy arms
Measure:Complete response rate
Time Frame:5 years
Safety Issue:
Description:To evaluate and compare complete response rate in each arm, which is defined as the percentage of patients who show complete response as per ir-RECIST criteria
Measure:Time to progression
Time Frame:5 years
Safety Issue:
Description:To evaluate and compare time to progression (TTP), which is defined as time between date of registration and date of documented progression, between the experimental and control arms.
Measure:Median response duration
Time Frame:5 years
Safety Issue:
Description:To evaluate and compare median response duration, which is defined as the time between the date a response (CR or PR) was first seen until date of progression, between the two arms
Measure:Toxicity
Time Frame:5 years
Safety Issue:
Description:To evaluate the tolerability and toxicity in each arm as measured according to CTCAE v4.0.
Measure:Health-related quality of life
Time Frame:5 years
Safety Issue:
Description:To compare health-related quality of life (HR-QoL) between the experimental and control arms.
Measure:immunogenicity
Time Frame:5 years
Safety Issue:
Description:To measure and compare treatment-related tumor-specific immune response (immunogenicity) in each arm
Measure:Immunological biomarkers
Time Frame:5 years
Safety Issue:
Description:To identify immunological biomarkers as predictors of treatment response or resistance.
Measure:Cost-effectiveness
Time Frame:5 years
Safety Issue:
Description:To evaluate the cost-effectiveness and cost-utility of the addition of SAbR to Nivolumab in patients with mRCC

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Texas Southwestern Medical Center

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