Clinical Trials /

Trial of SBRT in Combination With Nivolumab/Ipilimumab in RCC / Kidney Cancer Patients

NCT03065179

Description:

This is a multi-institution, single-arm phase II study to determine the safety and efficacy of SBRT (up to 2 metastatic sites preferentially lung, mediastinum or bone in combination of nivolumab and ipilimumab in patients with metastatic renal cell carcinoma(with a clear-cell component and at least 1 measurable metastatic lesion that is not being irradiated).

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Trial of SBRT in Combination With Nivolumab/Ipilimumab in RCC / Kidney Cancer Patients
  • Official Title: Phase II Trial of Stereotactic Body Radiation Therapy in Combination With Nivolumab Plus Ipilimumab in Patients With Metastatic Renal Cell Cancer

Clinical Trial IDs

  • ORG STUDY ID: STU072016/044
  • NCT ID: NCT03065179

Conditions

  • Kidney Cancer Metastatic
  • Kidney Cancer
  • Kidney Cancer, Stage IV

Interventions

DrugSynonymsArms
Nivolumab/IpilimumabOpdivo, YervoyNivolumab/Ipilimumab plus SBRT

Purpose

This is a multi-institution, single-arm phase II study to determine the safety and efficacy of SBRT (up to 2 metastatic sites preferentially lung, mediastinum or bone in combination of nivolumab and ipilimumab in patients with metastatic renal cell carcinoma(with a clear-cell component and at least 1 measurable metastatic lesion that is not being irradiated).

Detailed Description

      The study is planned based on a two-stage design that allows early termination for lack of
      efficacy. A safety run-in phase will be included comprising the first 6 patients at minimum
      to ensure that the combination of nivolumab plus ipilimumab and SBRT is safe. Then, the
      investigators will determine whether the combination of nivolumab plus ipilimumab and SBRT
      yields a clinically compelling antitumor activity measured as ORR, and evaluate other
      endpoints including TTP, DOR, PFS, OS and local control of irradiated sites.

      There is no previous experience with SBRT used concurrently with nivolumab and ipilimumab in
      this study population. Therefore, to ensure that the combination is safe, the first six
      patients will be treated and observed for toxicity for 6 weeks after radiation before
      continuing with further accrual. Therefore, six patients will be enrolled at the proposed
      dose of nivolumab and ipilimumab in combination with SBRT. If 4 out of the first 6 patients
      experience Grade 3/4 toxicity or a lower grade toxicity requiring immune suppressive therapy
      during the safety run-in observation period (defined as the first 4-cycles, 12 weeks),
      enrollment will cease and the study will be halted until further safety analysis of the
      combination regimen can be performed. If less than 4 out of the first 6 patients experience
      Grade 3/4 toxicities or require steroids, the investigators will proceed with additional
      accrual with this regimen.
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab/Ipilimumab plus SBRTExperimentalInduction Dual Immune Checkpoint Inhibition with nivolumab and ipilimumab plus SBRT to 1-2 metastatic sites, followed by nivolumab monotherapy
  • Nivolumab/Ipilimumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histological confirmation of RCC with a clear-cell component

          -  Metastatic (AJCC Stage IV) RCC

          -  Prior adjuvant or neoadjuvant therapy for localized or locally advanced RCC is
             allowed provided recurrence occurred = or > 6 months after the last dose of the
             adjuvant or neoadjuvant therapy

          -  Any number of prior systemic treatment regimen in the advanced/metastatic setting is
             allowed (cytokine, anti-angiogenic, mTOR inhibitor or clinical trial) including
             previously untreated patients

          -  Karnofsky Performance Status (KPS) of at least 70%

          -  Life expectancy of at least 3 months

          -  At least 2 metastatic sites of which at least 1 must be measurable as per RECIST 1.1

          -  Archival Formalin-fixed paraffin-embedded (FFPE) tumor tissue must be available for
             correlative studies (Note: Fine Needle Aspiration [FNA] and bone metastases samples
             are not acceptable for submission)

          -  Patients with favorable, intermediate and poor risk categories will be eligible for
             the study. Patients must be categorized according to favorable versus
             intermediate/poor risk status at registration. International Metastatic RCC Database
             Consortium (IMDC) must be used to determine prognostic factors

        Exclusion Criteria:

          -  Subjects with previously treated brain or CNS metastases are eligible provided that
             the subject has recovered from any acute effects of radiotherapy and is not requiring
             steroids, and any whole brain radiation therapy was completed at least 4 weeks prior
             to study drug administration, or any stereotactic radiosurgery was completed at least
             2 weeks prior to study drug administration. Liver metastases will not be included as
             part of the radiated lesions to be treated.

        Medical History and Concurrent Diseases:

          -  Prior treatment with an 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. Prior treatment with HD IL-2 is allowed.

          -  Any active or recent history of a known or suspected autoimmune disease or recent
             history of a syndrome that required systemic corticosteroids (> 10 mg daily
             prednisone equivalent) or immunosuppressive medications except for syndromes which
             would not be expected to recur in the absence of an external trigger. Subjects with
             vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune
             thyroiditis only requiring hormone replacement are permitted to enroll. Patients with
             psoriasis not requiring active, systemic treatment are allowed.

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

          -  Uncontrolled adrenal insufficiency

          -  Requirement for anti-coagulation with Coumadin, low molecular weight heparin and
             anti-thrombin inhibitors will be accepted if anticoagulation has been stable for at
             least 4 weeks and no recent history of prior bleeding complications.

          -  Prior malignancy 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 cervix, breast or low risk
             Gleason 6 prostate cancer

          -  Known history of testing positive for human immunodeficiency virus (HIV) or known
             acquired immunodeficiency syndrome (AIDS)

          -  Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic
             infection

          -  Known medical condition (eg, a condition associated with diarrhea or acute
             diverticulitis) that, in the investigator's opinion, would increase the risk
             associated with study participation or study drug administration or interfere with
             the interpretation of safety results

          -  Major surgery (eg, nephrectomy) less than 28 days prior to the first dose of study
             drug

          -  Anti-cancer therapy less than 14 days prior to the first dose of study drug or
             palliative, focal radiation therapy less than 14 days prior to the first dose of
             study drug

          -  Presence of any toxicities attributed to prior anti-cancer therapy, other than
             alopecia, that have not resolved to Grade 1 (NCI CTCAE v4) or baseline before
             administration of study drug

        Physical and Laboratory Test Findings:

          -  Any of the following laboratory test findings:

               -  WBC < 2,000/mm3

               -  Neutrophils < 1,500/mm3

               -  Platelets < 100,000/mm3

               -  AST or ALT > 3 x ULN (> 5 x ULN if liver metastases are present)

               -  Total Bilirubin > 1.5 x ULN (except subjects with Gilbert Syndrome, who can have
                  total bilirubin < 3.0 mg/dL)

               -  Serum creatinine > 1.5 x upper limit of normal (ULN) or creatinine clearance <
                  40 mL/min (measured or calculated by Cockroft-Gault formula)

        Allergies and Adverse Drug Reaction:

          -  History of severe hypersensitivity reaction to any monoclonal antibody or study drug
             components

        Other Exclusion Criteria:

          -  Prisoners or subject who are involuntarily incarcerated

          -  Not suitable for SBRT treatment

          -  Subjects who are compulsorily detained for treatment of either a psychiatric or
             physical illness
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety: Number of Participants with treatment related adverse events of special interest assessed by CTCAE 4.0
Time Frame:1 year
Safety Issue:
Description:Number of Participants with treatment related adverse events of special interest assessed by CTCAE 4.0 such as: Fatigue Skin reactions: including rash, itching, hives, redness, and dry skin Diarrhea Nausea Abdominal pain Decreased appetite Low red blood cells Fever Joint pain or pneumonitis

Secondary Outcome Measures

Measure:Efficacy: Objective Response Rate of slowing tumor growth or decrease in tumor size
Time Frame:1 year
Safety Issue:
Description:Objective Response Rate of slowing tumor growth or decrease in tumor size

Details

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

Last Updated

March 16, 2017