Randomized Phase II Stereotactic Ablative Radiation Therapy (SABR) for Metastatic Unresected Renal Cell Carcinoma (RCC) Receiving Immunotherapy (SAMURAI)

Plain English Summary

Testing the Addition of Stereotactic Radiation Therapy With Immune Therapy for the Treatment of Patients With Unresectable or Metastatic Renal Cell Cancer, SAMURAI Trial is a Phase 2 clinical trial sponsored by NRG Oncology studying Metastatic Renal Cell Carcinoma, Stage III Renal Cell Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Unresectable Renal Cell Carcinoma. This trial tests if adding a precise form of radiation therapy (SABR) to standard immunotherapy can help control advanced kidney cancer that has spread and cannot be removed by surgery. It is for patients with advanced kidney cancer that has spread to other parts of the body and is not suitable for surgery. Participants will receive standard immunotherapy, and some will also receive the new radiation therapy targeted at the main kidney tumor. Alternative treatments may include other forms of immunotherapy or targeted drugs, depending on the patient's specific situation and prior treatments. The trial aims to enroll 240 participants.

Official Summary

This phase II trial tests whether the addition of radiation to the primary tumor, typically given with stereotactic ablative radiation therapy (SABR), in combination with standard of care immunotherapy improves outcomes in patients with renal cell cancer that is not recommended for surgery and has spread from where it first started (primary site) to other places in the body (metastatic). Radiation therapy uses high energy photons to kill tumor cells and shrink tumors. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses of radiation over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, avelumab, and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib, cabozantinib, and lenvatinib are in a class of medications called antiangiogenic agents. They work by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving SABR in combination with standard of care immunotherapy may help shrink or stabilize the cancer in patients with renal cell cancer.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients with kidney cancer that has spread and cannot be surgically removed. Must have intermediate or poor risk disease based on specific factors. Must be at least 18 years old. Cannot have untreated or unstable brain tumors. This trial is studying Metastatic Renal Cell Carcinoma, Stage III Renal Cell Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Unresectable Renal Cell Carcinoma, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The main goal is to see how long patients live without their cancer getting worse or needing surgery for it, meaning the treatment is helping to control the disease for a longer period. The specific primary outcome measures are: Nephrectomy and radiographic progression-free survival (nrPFS) (From randomization to last follow-up, up to 8 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to improve treatment for advanced kidney cancer by combining a precise radiation technique with immunotherapy, addressing a need for more effective options when surgery is not possible Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Metastatic Renal Cell Carcinoma, Stage III Renal Cell Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Unresectable Renal Cell Carcinoma, where improved treatment options are needed.

Investor Insight

This trial targets a significant market for advanced kidney cancer treatments, exploring a novel combination therapy that could offer a competitive advantage if proven effective, potentially leading t Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if this trial is a good fit for your specific type and stage of kidney cancer. Understand that participation involves receiving standard immunotherapy, and potentially targeted radiation therapy, along with regular check-ups and scans. Be prepared for potential side effects from both immunotherapy and radiation therapy. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 240 participants

Interventions

• BIOLOGICAL: Avelumab — Given IV
• DRUG: Axitinib — Given PO
• PROCEDURE: Biospecimen Collection — Undergo collection of blood
• PROCEDURE: Bone Scan — Undergo bone scan
• DRUG: Cabozantinib — Given PO

Primary Outcomes

• Nephrectomy and radiographic progression-free survival (nrPFS) (From randomization to last follow-up, up to 8 years)

Secondary Outcomes

• Percentage of participants with complete or partial response (From randomization to disease progression)
• Percentage of participants with complete or partial response in the primary renal mass (From randomization to disease progression)
• Radiographic progression-free survival (rPFS) (From randomization to last follow-up, up to 8 years)
• Nephrectomy and radiographic progression-free survival excluding nephrectomies that were performed for non-protocol specified reasons (nrPFS2) (From randomization to last follow-up, up to 8 years)
• Overall survival (From randomization to last follow-up, up to 8 years)

Full Eligibility Criteria

Inclusion Criteria:

* Pathologically (histologically or cytologically) proven diagnosis of renal cell carcinoma prior to registration
* Node-positive unresectable (TxN1Mx) or metastatic (TxNxM1) based on the following diagnostic workup:

  * History/physical examination within 45 days prior to registration
  * CT/magnetic resonance imaging (MRI) of the chest/abdomen/pelvis within 45 days prior to registration
* Patients must have IMDC intermediate (1-2 factors) or poor risk disease (\>= 3 factors)
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with measurable disease (node positive or metastatic) as defined by RECIST version 1.1 excluding the primary renal tumor
* Patient not recommended for or refused immediate cytoreductive nephrectomy
* Candidate for standard of care therapy with either immuno-oncology (IO)-IO or IO-VEGF combination regimen
* Primary renal tumor measuring 20 cm or less in anterior to posterior dimension only on axial imaging
* Age \>= 18
* Karnofsky performance status \>= 60 within 45 days prior to registration
* Hemoglobin \>= 8 g/dL (transfusions are allowed) (within 45 days prior to registration)
* Platelet count \>= 50,000/mm\^3 (within 45 days prior to registration)
* Absolute neutrophil count (ANC) \>= 1500/mm\^3 (within 45 days prior to registration)
* Calculated (Calc.) creatinine clearance \>= 30 mL/min (within 45 days prior to registration)

  * Creatinine clearance (CrCl) \>= 30 mL/min estimated by Cockcroft-Gault Equation
  * For African American patients specifically whose renal function is not considered adequate by the formula above, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) should be used for calculating the related estimated glomerular filtration rate (GFR) with a correction factor for African American race creatinine clearance for trial eligibility, where GFR \>= 30 mL/min/1.73m\^2 will be considered adequate
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL) (within 45 days prior to registration)
* Aspartate aminotransferase and alanine aminotransferase (AST and ALT) =\< 3 x upper limit of normal (ULN) or \< 5 x ULN if hepatic metastases present (within 45 days prior to registration)
* Patients with known human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Testing is not required for entry into protocol
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load
* The patient must agree to use a highly effective contraception, including men with vasectomies if they are having sex with a woman of childbearing potential or with a woman who is pregnant, while on study drug and for 6 months following the last dose of study drug. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information

Exclusion Criteria:

* Patients with planned treatment of all metastatic disease with definitive therapy including either surgery, ablative (non-palliative) doses of radiation, or intervention of some type (definitive interventional radiology techniques) to ALL metastatic sites rendering the patient without extra-renal measurable disease. Patients NOT planned for definitive treatment of all metastatic sites are eligible. Lesions radiated palliatively are not eligible for response assessment
* Patients with untreated or unstable brain metastases or cranial epidural disease

  * Note: Patients who have been adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator are eligible. Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator
* Prior radiotherapy to the kidney that would result in overlap of radiation therapy fields treatment of the primary 

Trial Locations

• University of Alabama at Birmingham Cancer Center, Birmingham, Alabama, United States
• University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
• PCR Oncology, Arroyo Grande, California, United States
• Mills-Peninsula Medical Center, Burlingame, California, United States
• City of Hope Comprehensive Cancer Center, Duarte, California, United States
• UC San Diego Health System - Encinitas, Encinitas, California, United States
• UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care, Irvine, California, United States
• UC San Diego Moores Cancer Center, La Jolla, California, United States
• Los Angeles General Medical Center, Los Angeles, California, United States
• USC / Norris Comprehensive Cancer Center, Los Angeles, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Kidney Cancer
• Renal Cell Carcinoma
• Metastatic Cancer
• Unresectable Tumors
• Immunotherapy
• Radiation Therapy
• Targeted Therapy
• Oncology
• Nephrology
• Urologic Oncology

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