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

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ClinicalTrials.gov Identifier: NCT03065179
Recruitment Status : Recruiting
First Posted : February 27, 2017
Last Update Posted : June 20, 2018
Sponsor:
Information provided by (Responsible Party):
Hans Hammers, University of Texas Southwestern Medical Center

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Kidney Cancer Metastatic Kidney Cancer Kidney Cancer, Stage IV Drug: Nivolumab/Ipilimumab Radiation: SBRT Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Stereotactic Body Radiation Therapy in Combination With Nivolumab Plus Ipilimumab in Patients With Metastatic Renal Cell Cancer
Actual Study Start Date : March 1, 2017
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Cancer

Arm Intervention/treatment
Experimental: Nivolumab/Ipilimumab plus SBRT
Induction Dual Immune Checkpoint Inhibition with nivolumab and ipilimumab plus SBRT to 1-2 metastatic sites, followed by nivolumab monotherapy
Drug: Nivolumab/Ipilimumab
IV immunotherapy
Other Names:
  • Opdivo
  • Yervoy

Radiation: SBRT
SBRT will be delivered in conjunction with immunotherapy
Other Name: stereotactic radiation




Primary Outcome Measures :
  1. Safety: Number of Participants with treatment related adverse events of special interest assessed by CTCAE 4.0 [ Time Frame: 1 year ]

    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 :
  1. Efficacy: Objective Response Rate of slowing tumor growth or decrease in tumor size [ Time Frame: 1 year ]
    Objective Response Rate of slowing tumor growth or decrease in tumor size



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03065179


Contacts
Contact: Hans Hammers, MD, PhD 214-645-7445 Hans.Hammers@utsoutwestern.edu

Locations
United States, Maryland
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Not yet recruiting
Baltimore, Maryland, United States, 21287
United States, Texas
UT Southwestern Recruiting
Dallas, Texas, United States, 75390
Contact: Allison Beaver, BSN, RN    214-645-8787    Allison.Beaver@utsouthwestern.edu   
Principal Investigator: Hans Hammers, MD, PhD         
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Investigators
Principal Investigator: Hans Hammers, MD, PhD UT Southwestern Medical Center

Responsible Party: Hans Hammers, Associate Professor, Internal Medicine, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT03065179     History of Changes
Other Study ID Numbers: STU072016/044
First Posted: February 27, 2017    Key Record Dates
Last Update Posted: June 20, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Kidney Neoplasms
Carcinoma, Renal Cell
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Kidney Diseases
Urologic Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs