Focused Radiation vs Systemic Therapy for Kidney Cancer

Recruiting at 115 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

Trial Summary

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.

What data supports the effectiveness of this treatment for kidney cancer?

Research shows that stereotactic body radiotherapy (SBRT) is increasingly used for treating localized kidney cancer, especially in patients who cannot undergo surgery. Studies also suggest that SBRT can be safely combined with immunotherapy and targeted drugs for treating advanced kidney cancer, potentially improving outcomes. ^{1 2 3 4 5}

Is stereotactic body radiotherapy (SBRT) safe for treating kidney cancer?

Research shows that stereotactic body radiotherapy (SBRT) has been used safely in treating kidney cancer, including in patients who are not suitable for surgery. Studies have reported on its safety and tolerability, even in frail patients and those with advanced disease. ^{1 2 3 6 7}

How is the treatment of focused radiation and systemic therapy for kidney cancer different from other treatments?

This treatment is unique because it combines focused radiation, known as Stereotactic Ablative Radiotherapy (SABR), which precisely targets kidney tumors while sparing surrounding tissues, with systemic therapies like hormone therapy, chemotherapy, or immunotherapy. This approach is particularly beneficial for patients who cannot undergo surgery, offering a potent and shorter treatment course. ^{1 5 8 9 10}

What is the purpose of this trial?

This phase III trial compares the effect of stero-ablative radiotherapy (SAbR) followed by standard of care systemic therapy, to standard of care systemic therapy alone, in patients with kidney cancer that has spread from where it first started (primary site) to a limited (2-5) number of places in the body (metastatic). Study doctors want to find out if this approach is better or worse than the usual approach for metastatic kidney cancer. The usual approach is defined as the care most people get for metastatic kidney cancer which includes systemic therapy such as immunotherapy (given through the veins) and/or small molecular inhibitor (tablets taken by mouth). Radiotherapy uses high energy x-rays to kill cancer cells and shrink tumors. SAbR uses special equipment to position a patient and deliver radiation to tumors with high precision. Giving SAbR prior to systemic therapy may kill more tumor cells than the usual approach, which is systemic therapy alone.

Research Team

Raquibul Hannan

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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) 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]

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]

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]

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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiotherapy for Localized Kidney Cancer. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy in combination with non-frontline PD-1 inhibitors and targeted agents in metastatic renal cell carcinoma. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiotherapy for Frail Patients with Primary Renal Cell Carcinoma: Preliminary Results after 4 Years of Experience. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiotherapy for Renal Cell Carcinoma: Oncological and Renal Function Outcomes. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Radiation therapy options in kidney cancer. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Nephron-Sparing Robotic Radiosurgical Therapy for Primary Renal Cell Carcinoma: Single-Institution Experience and Review of the Literature. [2022]

7. Ireland pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of stereotactic body radiotherapy (SBRT) for poor surgical candidates with localized renal cell carcinoma. [2022]

8. China 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. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Image guidance and stabilization for stereotactic ablative body radiation therapy (SABR) treatment of primary kidney cancer. [2018]

10. Canada 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. [2020]