SBRT With Combination Ipilimumab/Nivolumab for Metastatic Kidney Cancer

NCT ID: NCT04090710

Last Updated: 2025-08-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-29
• Study Completion Date: 2026-04-30

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.

Conditions

Metastatic Renal Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Ipilimumab/ Nivolumab

Intervention Type: 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

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.

Group Type: EXPERIMENTAL

SBRT + Ipilimumab/Nivolumab

Intervention Type: 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.

Interventions

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

Intervention Type: DRUG

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.

Intervention Type: RADIATION

Other Intervention Names

Yervoy/Opdivo

Eligibility Criteria

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.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Ontario Clinical Oncology Group (OCOG)

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Aly-Khan Lalani, MD

Role: PRINCIPAL_INVESTIGATOR

Juravinski Cancer Centre

Locations

Peter MacCallum Cancer Centre

Melbourne, , Australia

Cross Cancer Institute

Edmonton, Alberta, Canada

Juravinski Cancer Centre

Hamilton, Ontario, Canada

Grand River Regional Cancer Centre

Kitchener, Ontario, Canada

London Regional Cancer Centre

London, Ontario, Canada

The Ottawa Regional Cancer Centre

Ottawa, Ontario, Canada

Sunnybrook Health Sciences Centre- Odette Cancer Centre

Toronto, Ontario, Canada

Countries

Australia; Canada

Other Identifiers

CA209-7DR

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

OCOG-2019-CYTOSHRINK

Identifier Type: -

Identifier Source: org_study_id