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SBRT With Combination Ipilimumab/Nivolumab for Metastatic Kidney Cancer (CYTOSHRINK)

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ClinicalTrials.gov Identifier: NCT04090710
Recruitment Status : Recruiting
First Posted : September 16, 2019
Last Update Posted : January 31, 2020
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Ontario Clinical Oncology Group (OCOG)

Tracking Information
First Submitted Date  ICMJE September 9, 2019
First Posted Date  ICMJE September 16, 2019
Last Update Posted Date January 31, 2020
Actual Study Start Date  ICMJE January 29, 2020
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 12, 2019)
Progression free survival (PFS) [ Time Frame: 2 years ]
The primary outcome of this study is the hazard ratio for progression-free survival (PFS), defined from the date of randomization until the date of progression (PFS truncated at subsequent systemic therapy) as determined by RECIST 1.1, or death due to any cause, whichever comes first. All attempts will be made to follow-up patients for the primary outcome measure for at least one year, even if a patient stops treatment. Patients who do not have a primary outcome event at the time of analysis will be censored on the last date the patient can be confirmed as alive and progression-free.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2019)
  • Subject safety [ Time Frame: Date of randomization until 1year post treatment ]
    Incidence and attribution of deaths
  • Overall Survival [ Time Frame: 2 years ]
    • Overall survival, defined from the date of randomization to the date of death due to any cause. Patients with no known death date at the time of analysis will be censored on the last date they are confirmed alive.
  • Objective response rate [ Time Frame: 1 year ]
    • Objective response rate, which is defined as the proportion of randomized subjects who achieve a best response of complete response (CR) or partial response (PR) using the RECIST 1.1 criteria.
  • Quality of Life: EORTC QLQ-C30 questionnaire [ Time Frame: 1 year ]
    • Quality of life, which will be evaluated using the EORTC QLQ-C30 questionnaire.
  • Subject safety [ Time Frame: 1 Year ]
    Number of Adverse Events and Serious Adverse Events using NCI CTCAE v5.0
  • Ipilimumab/ Nivolumab drug tolerability [ Time Frame: From the date of randomization until date of first documented disease progression up to 1 year. ]
    Ipilimumab/Nivolumab treatment discontinuation rates
  • Ipilimumab/ Nivolumab drug tolerability [ Time Frame: From the date of randomization until date of first documented disease progression, up to 1 year. ]
    Number of doses of Ipilimumab/Nivolumab combination treatment
  • Ipilimumab/ Nivolumab drug tolerability [ Time Frame: From the date of randomization until date of first documented disease progression, up to 1 year. ]
    Number of Nivolumab maintenance doses
  • Ipilimumab/ Nivolumab drug tolerability [ Time Frame: From the date of randomization until date of first documented disease progression, up to 1 year. ]
    Time to treatment discontinuation from the date of randomization
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: September 12, 2019)
  • Exploratory Outcomes: Evaluation of baseline and changes during treatment in blood immune signatures [ Time Frame: 1 year ]
    Changes in blood immune signatures through interrogation of circulating blood biomarkers.
  • Exploratory Outcomes: Evaluation of baseline and changes during treatment in stool microbiome [ Time Frame: 1 year ]
    Changes in stool microbiome using 16S RNA.
  • Correlation with blood or stool immune signatures [ Time Frame: 1 year ]
    Tumor tissue analysis using immunohistochemistry
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE SBRT With Combination Ipilimumab/Nivolumab for Metastatic Kidney Cancer
Official Title  ICMJE Cytoreductive Stereotactic Hypofractionated Radiotherapy With Combination Ipilimumab/Nivolumab for Metastatic Kidney Cancer
Brief Summary This trial will evaluate the addition of cytoreductive stereotactic body radiation therapy (SBRT) to standard of care combination ipilimumab and nivolumab (I/N) versus I/N alone for the treatment of metastatic kidney cancer.
Detailed Description

This is a multi-centre, open label, phase II randomized clinical trial evaluating SBRT as upfront cytoreductive therapy to the primary renal mass along with combination I/N therapy in patients with intermediate/poor risk mRCC who are not candidates for cytoreductive nephrectomy. Eligible and consenting, newly diagnosed and histologically confirmed intermediate/poor risk mRCC patients based on IMDC criteria with primary disease in-situ will be randomized in a 2:1 fashion to either induction I/N followed by SBRT prior to the second cycle (experimental arm) versus I/N alone (standard arm). Patients will be stratified based on IMDC criteria (intermediate 1-2 versus poor 3-6).

  • Standard Arm: induction ipilimumab 1 mg/kg combined with nivolumab 3 mg/kg (I/N) every 3 weeks for cycles 1-4 followed by maintenance treatment with nivolumab 240mg every 2 weeks or 480mg every 4 weeks until disease progression (as determined by RECIST 1.1), intolerance, or patient/physician decision to stop treatment.
  • Experimental Arm: induction ipilimumab 1 mg/kg combined with nivolumab 3 mg/kg (I/N) every 3 weeks for one cycle, followed by SBRT to the primary disease in-situ, prior to cycle 2-4 of I/N. Patients randomized to SBRT will undergo radiation planning during the first cycle of I/N to their primary kidney mass, and then the radiation will be delivered between cycles 1 and 2 to a dose of 30-40 Gy in 5 fractions every other day over 1.5 weeks. Approximately one week following completion of SBRT, patients will start cycle 2 of I/N as per standard of care. The total time elapsed between the start of cycle 1 and 2 of I/N should be no more than 6 weeks. After completion of up to four cycles of I/N, patients will proceed to standard of care maintenance treatment with nivolumab 240mg every 2 weeks or 480mg every 4 weeks until disease progression (as determined by RECIST 1.1), intolerance, or patient/physician decision to stop treatment.

During treatment (standard and experimental arm) participants will be assessed for radiation toxicity and the occurrence of adverse events. Following treatment, participants will be assessed at a clinic visit every 3 months, for a period of 1 year. Progression free survival will be assessed by CT scan (chest; abdomen and pelvis), which is performed after the final I/N treatment and every 3 months as per standard of care. Participants will be followed for one additional year, seen at 18 and 24 months to assess survival. The planned sample size is 78 study participants.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Eligible and consenting, newly diagnosed and histologically confirmed intermediate/poor risk metastatic renal cell carcinoma patients with primary disease in-situ will be randomized in a 2:1 fashion to either induction I/N followed by SBRT prior to the second cycle (experimental arm) versus I/N alone (standard arm). Patients will be stratified based on IMDC criteria (intermediate 1-2 versus poor 3-6).
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Renal Cell Carcinoma
Intervention  ICMJE
  • Drug: Ipilimumab/ Nivolumab
    induction ipilimumab 1 mg/kg combined with nivolumab 3 mg/kg (I/N) every 3 weeks for cycles 1-4 followed by maintenance treatment with nivolumab 240mg every 2 weeks or 480mg every 4 weeks until disease progression
    Other Name: Yervoy/Opdivo
  • Radiation: SBRT + Ipilimumab/Nivolumab
    SBRT to the primary disease in-situ, prior to cycle 2-4 of I/N. Patients randomized to SBRT will undergo radiation planning during the first cycle of I/N to their primary kidney mass, and then the radiation will be delivered between cycles 1 and 2 to a dose of 30-40 Gy in 5 fractions every other day over 1.5 weeks.
Study Arms  ICMJE
  • Active Comparator: Standard of Care I/N alone
    induction ipilimumab 1 mg/kg combined with nivolumab 3 mg/kg (I/N) every 3 weeks for cycles 1-4 followed by maintenance treatment with nivolumab 240mg every 2 weeks or 480mg every 4 weeks until disease progression (as determined by RECIST 1.1), intolerance, or patient/physician decision to stop treatment.
    Intervention: Drug: Ipilimumab/ Nivolumab
  • Experimental: Standard of Care I/N plus primary disease SBRT
    induction ipilimumab 1 mg/kg combined with nivolumab 3 mg/kg (I/N) every 3 weeks for one cycle, followed by SBRT to the primary disease in-situ, prior to cycle 2-4 of I/N. Patients randomized to SBRT will undergo radiation planning during the first cycle of I/N to their primary kidney mass, and then the radiation will be delivered between cycles 1 and 2 to a dose of 30-40 Gy in 5 fractions every other day over 1.5 weeks. Approximately one week following completion of SBRT, patients will start cycle 2 of immunotherapy as per standard of care. The total time elapsed between the start of cycle 1 and 2 of I/N should be no more than 6 weeks. After completion of up to four cycles of I/N, patients will proceed to standard of care maintenance treatment with nivolumab 240mg every 2 weeks or 480mg every 4 weeks until disease progression (as determined by RECIST 1.1), intolerance, or patient/physician decision to stop treatment.
    Intervention: Radiation: SBRT + Ipilimumab/Nivolumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 12, 2019)
78
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2023
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Biopsy proven renal cell carcinoma of any histology.
  2. Imaging proven metastatic disease based on CT or MRI within 10 weeks of screening.
  3. Intermediate/poor risk disease based on IMDC criteria (see Appendix II).
  4. Primary kidney lesion amenable to SBRT.
  5. Eligible for standard of care delivery of ipilimumab and nivolumab (I/N) according to approved product monograph.

Exclusion Criteria:

  1. A maximum primary renal lesion size of 20 cm or greater.
  2. Candidate for cytoreductive nephrectomy, unless a patient has refused cytoreductive nephrectomy (in this case, a discussion of cytoreductive nephrectomy and patient refusal must be documented).
  3. Treatment with prior systemic therapy in the adjuvant or metastatic setting for renal cell carcinoma.
  4. Previous abdominal radiation precluding SBRT.
  5. Kanofsky Performance (KPS) score below 60 (see Appendix III).
  6. History of auto-immune disorder precluding treatment with ipilimumab or nivolumab.
  7. History of ataxia telangiectasia or other radiation sensitivity disorders.
  8. Chronic corticosteroid use or other chronic immune suppressive therapy. (Participants are permitted the use of topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Adrenal replacement steroid doses of prednisone ≤ 10 mg daily are permitted).
  9. Use of medicinal herbal preparations (not including medical cannabis) unless prescribed by a treating physician.
  10. Inability to lie flat for at least 30 minutes without moving.
  11. Pregnant or lactating women.
  12. Geographic inaccessibility for follow-up.
  13. Inability to provide informed consent.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lisa Rudd-Scott, RN BScN MN 905-527-2299 ext 43793 ruddl@mcmaster.ca
Contact: Erin McGean 905-527-2299 ext 42656 mcgeane@mcmaster.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04090710
Other Study ID Numbers  ICMJE OCOG-2019-CYTOSHRINK
CA209-7DR ( Other Grant/Funding Number: BMS )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Ontario Clinical Oncology Group (OCOG)
Study Sponsor  ICMJE Ontario Clinical Oncology Group (OCOG)
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Principal Investigator: Aly-Khan Lalani, MD Juravinski Cancer Centre
PRS Account Ontario Clinical Oncology Group (OCOG)
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP