SBRT + Immunotherapy for Kidney Cancer

(CYTOSHRINK Trial)

Not currently recruiting at 7 trial locations

Overseen By Lisa Rudd-Scott, RN BScN MN

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Ontario Clinical Oncology Group (OCOG)

Must be taking: Ipilimumab, Nivolumab

Must not be taking: Chronic corticosteroids, Herbal preparations

Disqualifiers: Large renal lesion, Auto-immune disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding a specialized form of radiation therapy (SBRT) to the usual combination of two immunotherapy drugs, ipilimumab and nivolumab, can more effectively treat metastatic kidney cancer that has spread. Participants will receive either the standard immunotherapy alone or the immunotherapy plus radiation targeted at the kidney tumor. Suitable candidates for this trial have kidney cancer confirmed by a biopsy, visible cancer spread on recent scans, and tumors treatable by this special radiation. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those on chronic corticosteroids or immune suppressive therapy, except for certain low-dose or topical forms. It also excludes those using medicinal herbal preparations unless prescribed by a doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of ipilimumab and nivolumab is generally safe for treating kidney cancer. Studies found that patients using this combination had a 37% lower risk of dying compared to those using another treatment. However, some patients experienced side effects like tiredness and skin rash, which are common but usually manageable.

Regarding stereotactic body radiation therapy (SBRT), research suggests it is well-tolerated by patients with kidney cancer. Most studies report good results with only minor side effects, such as mild tiredness or skin irritation, which typically resolve on their own.

Overall, treatments in this trial have been used in other studies and have shown safety for most patients. However, discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining SBRT (stereotactic body radiation therapy) with immunotherapy treatments like ipilimumab and nivolumab for kidney cancer because it offers a unique approach to treatment. Unlike standard immunotherapy alone, this combination uses SBRT to directly target and shrink the kidney tumor with precise radiation, potentially boosting the effectiveness of the immune response triggered by the drugs. This strategy aims to enhance the body's ability to fight cancer by first reducing the tumor size, then allowing the immunotherapy to work more effectively, which could lead to improved outcomes for patients.

What evidence suggests that this trial's treatments could be effective for metastatic kidney cancer?

Research has shown that using ipilimumab and nivolumab together effectively treats advanced kidney cancer. In one study, patients taking these drugs had a 37% lower risk of death compared to those using another treatment called SUTENT. Another long-term study found a 28% reduction in the risk of death, confirming its effectiveness over time. In this trial, one group of participants will receive this combination therapy alone. Another group will receive the combination therapy along with stereotactic body radiation therapy (SBRT), which has effectively controlled local kidney cancer while preserving kidney function. Together, these treatments aim to provide a stronger defense against kidney cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Aly-Khan Lalani, MD

Principal Investigator

Juravinski Cancer Centre

Are You a Good Fit for This Trial?

This trial is for adults with biopsy-proven metastatic kidney cancer, who haven't had systemic therapy for it and can lie still for at least 30 minutes. They should be at an intermediate/poor risk level and have a primary kidney lesion small enough (<20 cm) to be treated with SBRT. Patients must not have plans for nephrectomy, previous abdominal radiation that prevents SBRT use, severe autoimmune disorders, or be on chronic immune suppressive drugs.

Inclusion Criteria

My kidney cancer diagnosis was confirmed with a biopsy.

My kidney tumor can be treated with targeted radiation.

My condition is considered intermediate or poor risk.

Exclusion Criteria

I've had radiation in my abdomen that prevents further targeted radiation.

I only use herbal medicines if they are prescribed by my doctor.

I have an autoimmune disease that prevents me from taking certain cancer treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Induction ipilimumab combined with nivolumab every 3 weeks for cycles 1-4

12 weeks

4 visits (in-person)

Radiation (Experimental Arm)

SBRT to the primary disease in-situ, delivered between cycles 1 and 2 of I/N

1.5 weeks

5 visits (in-person)

Maintenance Treatment

Nivolumab maintenance treatment every 2 or 4 weeks until disease progression or intolerance

Until disease progression

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Clinic visits every 3 months for 1 year, then at 18 and 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab/Nivolumab
• SBRT

Trial Overview The study compares two approaches: one group will receive standard care ipilimumab/nivolumab (I/N) treatment alone; the other group will get I/N plus stereotactic body radiation therapy (SBRT). The goal is to see if adding SBRT improves outcomes in metastatic kidney cancer patients.

How Is the Trial Designed?

Group I: Standard of Care I/N plus primary disease SBRT Experimental Treatment 1 Intervention

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 II: Standard of Care I/N alone Active Control 1 Intervention

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.

Ipilimumab/Nivolumab is already approved in United States, European Union, Japan, Canada for the following indications:

Approved in United States as Yervoy/Opdivo for:

• Melanoma
• Non-Small Cell Lung Cancer (NSCLC)
• Hepatocellular Carcinoma (HCC)
• Colorectal Cancer (MSI-H or dMMR)

Approved in European Union as Yervoy/Opdivo for:

• Melanoma
• Non-Small Cell Lung Cancer (NSCLC)
• Hepatocellular Carcinoma (HCC)
• Colorectal Cancer (MSI-H or dMMR)

Approved in Japan as Yervoy/Opdivo for:

• Melanoma
• Non-Small Cell Lung Cancer (NSCLC)
• Hepatocellular Carcinoma (HCC)

Approved in Canada as Yervoy/Opdivo for:

• Melanoma
• Non-Small Cell Lung Cancer (NSCLC)
• Hepatocellular Carcinoma (HCC)
• Colorectal Cancer (MSI-H or dMMR)

Who Is Running the Clinical Trial?

Ontario Clinical Oncology Group (OCOG)

Lead Sponsor

Trials

65

Recruited

42,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

In a study of 74 patients with metastatic renal cell carcinoma, adding stereotactic body radiotherapy (SBRT) to non-first-line PD-1 inhibitors and targeted agents significantly improved overall survival, with a median of 38.5 months compared to 15.4 months for those receiving only anti-PD-1/TA therapy.

The combination of SBRT with anti-PD-1/TA therapy was found to be safe and tolerable, with a similar rate of severe toxicities (54.8% in the SBRT group vs. 65.6% in the anti-PD-1/TA alone group), suggesting that this approach could be beneficial for patients, especially those with clear-cell type renal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy in combination with non-frontline PD-1 inhibitors and targeted agents in metastatic renal cell carcinoma. Liu, Y., Zhang, Z., Liu, R., et al.[2023]

In a study of 46 patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab, 72% experienced immune-related adverse events (irAEs), which were linked to significantly longer progression-free survival (PFS) compared to those without irAEs.

While irAE development was an independent predictor of longer PFS, it did not affect overall survival (OS), suggesting that irAEs could serve as a useful prognostic marker for treatment outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic impact of immune-related adverse events in metastatic renal cell carcinoma treated with nivolumab plus ipilimumab. Ikeda, T., Ishihara, H., Nemoto, Y., et al.[2022]

In a phase 3 trial involving 1096 patients with untreated advanced renal-cell carcinoma, nivolumab plus ipilimumab significantly improved overall survival rates (75% at 18 months) compared to sunitinib (60% at 18 months), indicating a more effective treatment option for patients with intermediate or poor prognostic risk.

The objective response rate was also higher with nivolumab plus ipilimumab (42%) compared to sunitinib (27%), although both treatments had a high incidence of treatment-related adverse events, with nivolumab plus ipilimumab showing a slightly lower rate of severe (grade 3 or 4) events (46% vs. 63%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. Motzer, RJ., Tannir, NM., McDermott, DF., et al.[2022]

In a real-world analysis of adverse events from two combination therapies for advanced renal cell carcinoma, cabozantinib (CAB) plus nivolumab (NIVO) showed higher incidence rates of seven types of toxicities compared to ipilimumab (IPI) plus NIVO.

Conversely, IPI + NIVO was associated with higher rates of three types of toxicities and had a greater incidence of serious adverse events, suggesting that both therapies have distinct safety profiles that can guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab. Blas, L., Shiota, M., Tsukahara, S., et al.[2023]

In a study of 69 patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab, those who experienced immune-related adverse events (irAEs) had significantly better overall survival (OS) and progression-free survival compared to those without irAEs, suggesting that irAEs may be a positive indicator of treatment response.

The study identified three key factors influencing OS: the presence of irAEs, C-reactive protein levels, and performance status, indicating that monitoring these factors could help predict patient outcomes in mRCC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic Impact of Immune-Related Adverse Events as First-Line Therapy for Metastatic Renal Cell Carcinoma Treated With Nivolumab Plus Ipilimumab: A Multicenter Retrospective Study. Nukaya, T., Takahara, K., Yoshizawa, A., et al.[2023]

In a study of 52 patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab, the 1-year progression-free survival rate was 55% and the overall survival rate was 75%, indicating promising efficacy of this treatment combination.

The treatment was associated with a 39% objective response rate, and while 69% of patients experienced immune-related adverse events, the incidence of severe events was lower compared to previous studies, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of first-line nivolumab plus ipilimumab in patients with metastatic renal cell carcinoma: A multicenter retrospective study. Tanaka, T., Hatakeyama, S., Numakura, K., et al.[2021]

In a study of 45 Japanese patients with untreated metastatic renal cell carcinoma, the combination therapy of nivolumab and ipilimumab showed a 41.5% objective response rate and a median progression-free survival of 17.8 months over a 2-year follow-up period.

The 2-year analysis indicated that nivolumab plus ipilimumab therapy's effectiveness aligns with previous studies, and second-line therapy following this combination also demonstrated a 20% objective response rate with a median progression-free survival of 9.8 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world effectiveness of nivolumab plus ipilimumab and second-line therapy in Japanese untreated patients with metastatic renal cell carcinoma: 2-year analysis from a multicenter retrospective clinical study (J-cardinal study). Kojima, T., Kato, R., Sazuka, T., et al.[2022]

Citations

1. opdivo.com opdivo.com/advanced-kidney-cancer/clinical-trial-results/immunotherapy-combination

Clinical trial results for advanced kidney cancer (renal cell ... In the clinical trial, people given OPDIVO + YERVOY had a 37% lower risk of dying than those given SUTENT, and more than half of the people given OPDIVO + ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39705641/

Real-World Outcomes in Patients With Metastatic Renal ... This study provides data to support the understanding of the real-world utilization and long-term effectiveness of 1L NIVO + IPI in patients ...

3. news.bms.com news.bms.com/news/details/2024/Eight-Year-Data-for-Opdivo-nivolumab-Plus-Yervoy-ipilimumab-Continue-to-Demonstrate-Longest-Survival-Benefit-vs.-Sunitinib-Reported-in-Patients-with-Previously-Untreated-Advanced-or-Metastatic-Renal-Cell-Carcinoma/default.aspx

Eight-Year Data for Opdivo (nivolumab) Plus Yervoy ... Patients with previously untreated advanced or metastatic renal cell carcinoma treated with Opdivo plus Yervoy experienced a 28% reduction in the risk of death ...

4. ascopubs.org ascopubs.org/doi/10.1200/CCI.24.00132

Real-World Outcomes in Patients With Metastatic Renal ... This study provides data to support the understanding of the real-world utilization and long-term effectiveness of 1L NIVO + IPI in patients with I/P-risk mRCC.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38251783/

Real-world outcomes of nivolumab plus ipilimumab ... The 3-year follow-up data showed that nivolumab plus ipilimumab combination therapy exhibited a feasible effectiveness in real-world Japanese patients with ...