- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04090710
SBRT With Combination Ipilimumab/Nivolumab for Metastatic Kidney Cancer (CYTOSHRINK)
Cytoreductive Stereotactic Hypofractionated Radiotherapy With Combination Ipilimumab/Nivolumab for Metastatic Kidney Cancer
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Lisa Rudd-Scott, RN BScN MN
- Phone Number: 43793 905-527-2299
- Email: ruddl@mcmaster.ca
Study Contact Backup
- Name: Erin McGean
- Phone Number: 42656 905-527-2299
- Email: mcgeane@mcmaster.ca
Study Locations
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Melbourne, Australia, 3000
- Peter MacCallum Cancer Centre
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Alberta
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Edmonton, Alberta, Canada, T6G 1Z2
- Cross Cancer Institute
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Ontario
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Hamilton, Ontario, Canada
- Juravinski Cancer Centre
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Kitchener, Ontario, Canada, N2G1G3
- Grand River Regional Cancer Centre
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London, Ontario, Canada, N2G1G3
- London Regional Cancer Centre
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Ottawa, Ontario, Canada, K1H8L6
- The Ottawa Regional Cancer Centre
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Toronto, Ontario, Canada, M4N3M5
- Sunnybrook Health Sciences Centre- Odette Cancer Centre
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Biopsy proven renal cell carcinoma of any histology.
- Imaging proven metastatic disease based on CT or MRI within 10 weeks of screening.
- Intermediate/poor risk disease based on IMDC criteria (see Appendix II).
- Primary kidney lesion amenable to SBRT.
- Eligible for standard of care delivery of ipilimumab and nivolumab (I/N) according to approved product monograph.
Exclusion Criteria:
- A maximum primary renal lesion size of 20 cm or greater.
- 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).
- Treatment with prior systemic therapy in the adjuvant or metastatic setting for renal cell carcinoma.
- Previous abdominal radiation precluding SBRT.
- Kanofsky Performance (KPS) score below 60 (see Appendix III).
- History of auto-immune disorder precluding treatment with ipilimumab or nivolumab.
- History of ataxia telangiectasia or other radiation sensitivity disorders.
- 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).
- Use of medicinal herbal preparations (not including medical cannabis) unless prescribed by a treating physician.
- Inability to lie flat for at least 30 minutes without moving.
- Pregnant or lactating women.
- Geographic inaccessibility for follow-up.
- Inability to provide informed consent.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
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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 Names:
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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.
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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2 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Subject safety
Time Frame: Date of randomization until 1year post treatment
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Incidence and attribution of deaths
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Date of randomization until 1year post treatment
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Overall Survival
Time Frame: 2 years
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• 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.
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2 years
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Objective response rate
Time Frame: 1 year
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• 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.
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1 year
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Quality of Life: EORTC QLQ-C30 questionnaire
Time Frame: 1 year
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• Quality of life, which will be evaluated using the EORTC QLQ-C30 questionnaire.
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1 year
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Subject safety
Time Frame: 1 Year
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Number of Adverse Events and Serious Adverse Events using NCI CTCAE v5.0
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1 Year
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Ipilimumab/ Nivolumab drug tolerability
Time Frame: From the date of randomization until date of first documented disease progression up to 1 year.
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Ipilimumab/Nivolumab treatment discontinuation rates
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From the date of randomization until date of first documented disease progression up to 1 year.
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Ipilimumab/ Nivolumab drug tolerability
Time Frame: From the date of randomization until date of first documented disease progression, up to 1 year.
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Number of doses of Ipilimumab/Nivolumab combination treatment
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From the date of randomization until date of first documented disease progression, up to 1 year.
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Ipilimumab/ Nivolumab drug tolerability
Time Frame: From the date of randomization until date of first documented disease progression, up to 1 year.
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Number of Nivolumab maintenance doses
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From the date of randomization until date of first documented disease progression, up to 1 year.
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Ipilimumab/ Nivolumab drug tolerability
Time Frame: From the date of randomization until date of first documented disease progression, up to 1 year.
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Time to treatment discontinuation from the date of randomization
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From the date of randomization until date of first documented disease progression, up to 1 year.
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Exploratory Outcomes: Evaluation of baseline and changes during treatment in blood immune signatures
Time Frame: 1 year
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Changes in blood immune signatures through interrogation of circulating blood biomarkers.
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1 year
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Exploratory Outcomes: Evaluation of baseline and changes during treatment in stool microbiome
Time Frame: 1 year
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Changes in stool microbiome using 16S RNA.
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1 year
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Correlation with blood or stool immune signatures
Time Frame: 1 year
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Tumor tissue analysis using immunohistochemistry
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1 year
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Aly-Khan Lalani, MD, Juravinski Cancer Centre
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Kidney Diseases
- Urologic Diseases
- Adenocarcinoma
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Kidney Neoplasms
- Carcinoma, Renal Cell
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Nivolumab
- Ipilimumab
Other Study ID Numbers
- OCOG-2019-CYTOSHRINK
- CA209-7DR (Other Grant/Funding Number: BMS)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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