Focused Radiation vs Systemic Therapy for Kidney Cancer

Recruiting at 118 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: ECOG-ACRIN Cancer Research Group

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Brain metastases, Autoimmune disease, Hypertension, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

472 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a type of focused radiation, called Stereotactic Ablative Radiotherapy (SAbR), is more effective than the usual treatment for kidney cancer that has spread to a few areas in the body. Typically, treatment involves systemic therapy, such as immunotherapy or other oral medications. The trial compares patients receiving SAbR before systemic therapy to those receiving systemic therapy alone, with the hope that the combination might kill more cancer cells. Suitable candidates have kidney cancer that has not spread to the brain or certain other parts of the body and has metastasized to 2-5 locations. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that patients must not have received any prior systemic therapy for metastatic kidney cancer, except in the adjuvant setting. It's best to discuss your current medications with the trial team to get a clear answer.

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

Research has shown that stereotactic ablative radiotherapy (SAbR) is generally safe and well-tolerated for people with kidney cancer. Studies have found that SAbR can effectively treat renal cell carcinoma, the most common type of kidney cancer. This treatment uses precise, high-dose radiation to target tumors, and long-term research suggests it is safe for patients.

One study found that patients who received SAbR for kidney cancer had good safety outcomes over five years. Some side effects occurred, but they were usually mild and manageable. This indicates that patients generally tolerate the treatment well.

In this trial, patients will receive SAbR followed by standard systemic therapy. Systemic therapy, a common treatment, includes options like immunotherapy and small molecule inhibitors, which are well-known and have proven safety records. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about these treatments because they offer a fresh approach to tackling kidney cancer. Unlike the standard of care, which typically involves systemic therapy where drugs circulate throughout the body, stereotactic ablative radiotherapy (SAbR) precisely targets cancer cells with high-dose radiation. This targeted approach may lead to fewer side effects and potentially quicker results. Moreover, combining SAbR with systemic therapy could enhance the overall effectiveness by attacking cancer on multiple fronts, giving patients a better chance at controlling the disease.

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

Research has shown that Stereotactic Ablative Radiotherapy (SAbR), which participants in this trial may receive, is a promising treatment for kidney cancer. Studies indicate that SAbR effectively controls tumors and yields excellent results for patients. Long-term evidence suggests that SAbR is safe and reduces the risk of cancer returning in the treated area. Patients with various types of kidney cancer have experienced successful tumor control with SAbR. Overall, SAbR is a strong option for managing kidney cancer that has spread to a few areas in the body. ^{2 6 7 8 9}

Who Is on the Research Team?

Raquibul Hannan

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

Adults with kidney cancer that has spread to 2-5 other body parts, who've had local treatment for the primary tumor and are in good physical condition (ECOG 0-2). They must not be pregnant, have brain metastases, severe allergies to certain antibodies, recent heart issues or surgeries. People with HIV or hepatitis can join if treated and controlled.

Inclusion Criteria

I am HIV positive, on treatment, and my viral load is undetectable.

My heart function is classified as class 2B or better, despite my history of heart issues or treatments.

My hepatitis B is under control with treatment.

Exclusion Criteria

I have or had inflammatory bowel disease.

I have not had malabsorption syndrome in the last 30 days.

Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants undergo repeated SAbR until progression

Varies until progression

Multiple visits for SAbR sessions

Systemic Therapy

Participants receive standard of care systemic therapy

Up to 10 years or until progression

Regular visits for systemic therapy administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

CT or MRI throughout the trial

What Are the Treatments Tested in This Trial?

Interventions

• Stereotactic Ablative Radiotherapy
• Systemic Therapy

Trial Overview The trial is testing whether using focused radiation (SAbR) before standard systemic therapy (like immunotherapy or molecular inhibitors) is more effective than systemic therapy alone for treating limited metastatic kidney cancer.

How Is the Trial Designed?

Group I: Arm II (SAbR, usual care) Experimental Treatment 5 Interventions

Patients undergo repeated SAbR until progression and then receive standard of care systemic therapy on study. Patients undergo CT or MRI throughout the trial.

Group II: Arm I (usual care) Active Control 4 Interventions

Patients receive standard of care systemic therapy on study. Patients undergo CT or MRI throughout the trial.

Stereotactic Ablative Radiotherapy is already approved in European Union, United States, United Kingdom for the following indications:

Approved in European Union as Stereotactic Ablative Radiotherapy for:

• Early-stage non-small cell lung cancer
• Liver cancers
• Kidney cancers
• Bone metastasis
• Spinal metastasis
• Prostate cancers

Approved in United States as Stereotactic Ablative Radiotherapy for:

• Early-stage non-small cell lung cancer
• Liver cancers
• Kidney cancers
• Bone metastasis
• Spinal metastasis
• Prostate cancers

Approved in United Kingdom as Stereotactic Ablative Radiotherapy for:

• Early-stage non-small cell lung cancer
• Liver cancers
• Kidney cancers
• Bone metastasis
• Spinal metastasis
• Prostate cancers

Who Is Running the Clinical Trial?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 21 patients with stage I renal cancer treated with stereotactic body radiation therapy (SBRT), the local tumor control rate was an impressive 100% at 5 years, indicating high efficacy of this noninvasive treatment.

The treatment resulted in only minimal toxicity, with only three patients experiencing grade 1 side effects, suggesting that SBRT is a safe option for patients, especially those who refuse surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nephron-Sparing Robotic Radiosurgical Therapy for Primary Renal Cell Carcinoma: Single-Institution Experience and Review of the Literature. Peddada, AV., Anderson, D., Blasi, OC., et al.[2022]

A retrospective study of patients with non-small cell lung cancer and symptomatic renal metastases showed that stereotactic body radiation therapy (SBRT) is a safe and effective treatment, providing symptomatic relief and early tumor control for all patients.

SBRT minimizes damage to surrounding tissues and can be delivered in a short treatment course of no more than 5 sessions, making it a promising option for palliative care in cases of renal metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for metastases to the kidney in patients with non-small cell lung cancer: a new treatment paradigm for durable palliation. Verma, V., Simone, CB.[2022]

Stereotactic body radiation therapy (SBRT) shows over 95% local control for primary renal cell carcinoma (RCC) with limited grade 3-4 toxicity at ≤5%, indicating it is a highly effective and safe treatment option.

For metastatic RCC, SBRT achieves approximately 90% local control at one year, with an even lower incidence of grade 3-4 toxicity at around 1%, suggesting its potential as a preferred treatment method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy options in kidney cancer. Zaorsky, NG., Louie, AV., Siva, S.[2023]

Stereotactic body radiation therapy (SBRT) has been shown to be a safe and effective treatment for localized kidney cancers, achieving over 90% local control with minimal severe toxicity in patients who are not candidates for surgery.

Recent studies indicate that SBRT can effectively treat larger kidney tumors (greater than 5 cm), but further randomized clinical trials are needed to optimize treatment protocols and compare its outcomes to traditional surgical methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiotherapy for Localized Kidney Cancer. Rich, BJ., Noy, MA., Dal Pra, A.[2023]

In a clinical trial involving 32 patients with primary kidney cancer, stereotactic ablative body radiation therapy was successfully delivered with minimal intrafraction motion, showing a mean target displacement of only 1.3 mm during treatment.

The study demonstrated that kidney motion was not significantly affected by the presence of tumors, indicating that the treatment can be accurately administered without major adjustments for tumor-related movement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image guidance and stabilization for stereotactic ablative body radiation therapy (SABR) treatment of primary kidney cancer. Pham, D., Kron, T., Bressel, M., et al.[2018]

Stereotactic body radiotherapy (SBRT) demonstrated high local control rates (96%) and overall survival (83%) in a study of 23 frail patients with primary renal cell carcinoma (RCC) who were unfit for surgery, with a median follow-up of 22 months.

The treatment was well-tolerated, with no severe side effects (grade 3-4) reported, indicating that SBRT is a safe and effective alternative for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiotherapy for Frail Patients with Primary Renal Cell Carcinoma: Preliminary Results after 4 Years of Experience. Grelier, L., Baboudjian, M., Gondran-Tellier, B., et al.[2021]

In a study of 74 patients with localized renal cell carcinoma treated with stereotactic body radiotherapy (SBRT), the oncological outcomes were promising, with low rates of local failure (7.77% at 4 years) and distant metastasis (4.24% at 2 years).

However, there was a notable decline in renal function over time, with a median decrease in estimated glomerular filtration rate (eGFR) of -11.5 ml/min at 2 years, particularly in the treated kidney, while the contralateral kidney showed compensatory improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiotherapy for Renal Cell Carcinoma: Oncological and Renal Function Outcomes. Glicksman, RM., Cheung, P., Korol, R., et al.[2023]

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]

Stereotactic body radiotherapy (SBRT) for localized renal cell carcinoma (RCC) was well-tolerated in 19 patients aged 59-89, with no dose-limiting toxicities observed at doses up to 48Gy in 4 fractions.

Among the patients treated, 3 showed a partial response and 12 had stable disease, indicating that SBRT can be an effective treatment option for patients who are poor surgical candidates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of stereotactic body radiotherapy (SBRT) for poor surgical candidates with localized renal cell carcinoma. Ponsky, L., Lo, SS., Zhang, Y., et al.[2022]

A case study of a patient with renal cell carcinoma (RCC) demonstrated that stereotactic body radiation therapy (SBRT) can be an effective treatment option, as the patient has remained disease-free for 8 years after receiving the therapy.

The patient maintained stable renal function even after undergoing two courses of SBRT on her only functioning kidney, suggesting that SBRT may be a safe alternative for select RCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long term control and preservation of renal function after multiple courses of stereotactic body radiation therapy for renal cell carcinoma. Reddy, AV., Mills, MN., Liauw, SL., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40907772/

Efficacy of Stereotactic Ablative Body Radiotherapy (SABR) ... SABR provides excellent oncologic outcomes, irrespective of ccRCC or nccRCC histology.

2. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(22)00656-8/abstract

5-year outcomes after stereotactic ablative body ... SABR is effective and safe in the long term for patients with primary renal cell carcinoma. Single-fraction SABR might yield less local failure ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301625061929

Efficacy of Stereotactic Ablative Body Radiotherapy (SABR) ... While stereotactic ablative body radiotherapy (SABR) is associated with excellent local control for primary renal cell carcinoma (RCC), outcomes ...

4. thegreenjournal.com thegreenjournal.com/article/S0167-8140(24)00138-5/fulltext

Dose-response of localized renal cell carcinoma after ... This comprehensive meta-analysis of 724 patients across 22 studies evaludated the impact of BED escalation in SBRT on outcomes in primary RCC.

5. urotoday.com urotoday.com/conference-highlights/astro-2025/astro-2025-kidney-cancer/163517-astro-2025-ultra-hypofractionated-stereotactic-ablative-body-radiotherapy-sabr-for-primary-renal-cell-carcinoma-pooled-outcomes-from-the-fastrack-and-fastrack-ii-clinical-trials.html

ASTRO 2025: Ultra-Hypofractionated Stereotactic Ablative ... 5-year outcomes after stereotactic ablative body radiotherapy for primary renal cell carcinoma: an individual patient data meta-analysis from IROCK (the ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10698523/

Stereotactic ablative radiotherapy for primary renal cell ... 5-year outcomes after stereotactic ablative body radiotherapy for primary renal cell carcinoma: an individual patient data meta-analysis ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2405630824001563

Primary site stereotactic ablative body radiotherapy in ... Stereotactic ablative body radiotherapy (SABR) is an effective treatment for localized renal cell carcinoma (RCC). However, the role of primary site SABR ...

8. europeanurology.com europeanurology.com/article/S0302-2838(22)02468-X/fulltext

The Role of Stereotactic Ablative Body Radiotherapy in ... Clinical outcomes, safety, and key indications of SABR in RCC are summarised in Fig. 1. Fig. 1 Safety and efficacy of SABR in renal cell ...

9. practicalradonc.org practicalradonc.org/article/S1879-8500(24)00156-5/abstract

Stereotactic Body Radiation Therapy for Primary Renal ... Real-world practice patterns and safety of concurrent radiotherapy and cabozantinib in metastatic renal cell carcinoma