SBRT With Combination Ipilimumab/Nivolumab for Metastatic Kidney Cancer

NCT04090710 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: OCOG-2019-CYTOSHRINKCA209-7DR
• Study Type: interventional
• Target: 66
• Locations: 2 countries
• Sites: 7

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.

Conditions

Metastatic Renal Cell Carcinoma

Keywords

SBRT; Ipilimumab; Nivolumab

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  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.

  2 years

Secondary Outcomes (9)

• Subject safety

  Date of randomization until 1year post treatment

• Overall Survival

  2 years

• Objective response rate

  1 year

• Quality of Life: EORTC QLQ-C30 questionnaire

  1 year

• Subject safety

  1 Year

Other Outcomes (3)

• Exploratory Outcomes: Evaluation of baseline and changes during treatment in blood immune signatures

  1 year

• Exploratory Outcomes: Evaluation of baseline and changes during treatment in stool microbiome

  1 year

• Correlation with blood or stool immune signatures

  1 year

Study Arms (2)

Standard of Care I/N alone

ACTIVE COMPARATOR

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.

Drug: Ipilimumab/ Nivolumab

Standard of Care I/N plus primary disease SBRT

EXPERIMENTAL

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.

Radiation: SBRT + Ipilimumab/Nivolumab

Interventions

Ipilimumab/ Nivolumab DRUG

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

Also known as: Yervoy/Opdivo

Standard of Care I/N alone

SBRT + Ipilimumab/Nivolumab RADIATION

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.

Standard of Care I/N plus primary disease SBRT

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ontario Clinical Oncology Group (OCOG): lead
• Bristol-Myers Squibb: collaborator

Study Sites (7)

Peter MacCallum Cancer Centre

Melbourne, 3000, Australia

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, Canada

Location

Grand River Regional Cancer Centre

Kitchener, Ontario, N2G1G3, Canada

Location

London Regional Cancer Centre

London, Ontario, N2G1G3, Canada

Location

The Ottawa Regional Cancer Centre

Ottawa, Ontario, K1H8L6, Canada

Location

Sunnybrook Health Sciences Centre- Odette Cancer Centre

Toronto, Ontario, M4N3M5, Canada

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Ipilimumab; Nivolumab; Radiosurgery

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Aly-Khan Lalani, MD

  Juravinski Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: September 9, 2019
• First Posted: September 16, 2019
• Study Start: January 29, 2020
• Primary Completion: April 30, 2026
• Study Completion: April 30, 2026
• Last Updated: August 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (6); AU (1)