Clinical trial Recruiting at 340 sites Phase 3 Interventional Ages 18 and up

Comparing immunotherapy with and without kidney surgery for metastatic kidney cancer

Official title: Phase III Trial of Immunotherapy-Based Combination Therapy With or Without Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma (PROBE Trial)

Run by SWOG Cancer Research Network · NCT04510597 · Data updated 2026-11-12

This study is testing whether adding kidney surgery to a standard immunotherapy treatment can help people with advanced kidney cancer live longer and feel better.

Quick facts

PhasePhase 3
Study typeInterventional
Ages18 Years and up
SexAll
Enrollment364 (estimated)
SponsorSWOG Cancer Research Network
Research network
Drugs / interventionsnivolumab, ipilimumab, pembrolizumab, avelumab, immunotherapy, Axitinib
Locations387 sites (Birmingham, Alabama and 386 other locations)
StatusRecruiting
StartedMarch 8, 2021
Main results expectedJuly 2033
Study endsJuly 2033
Registry record updatedOctober 8, 2026
Trial IDNCT04510597 on ClinicalTrials.gov

Is this trial a fit for you?

Likely a good fit

Ideal candidates include individuals with newly diagnosed metastatic renal cell carcinoma who have not received prior treatment.

Probably not a fit

Patients with collecting duct carcinoma or those who have already undergone treatment for their kidney cancer may not benefit from this study.

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This phase III trial evaluates the effectiveness of adding surgery to a standard immunotherapy-based drug combination in patients with metastatic renal cell carcinoma. Participants will be randomized to receive either the immunotherapy combination alone or with cytoreductive nephrectomy, which involves the surgical removal of the kidney. The study aims to compare overall survival rates and assess complications and response rates between the two treatment arms. Additionally, specimens will be banked for future studies to further understand treatment effects.

Why it matters

Potential benefit: If successful, this study could provide insights into whether combining surgery with immunotherapy improves survival outcomes for patients with metastatic kidney cancer.

How similar studies have gone: Other studies have explored immunotherapy for kidney cancer, but the specific combination of surgery with immunotherapy in this context is relatively novel.

Who can join: the full rules

Show full inclusion / exclusion criteria
Inclusion Criteria:

* STEP 1 REGISTRATION: Participants must have a histologically proven diagnosis of clear cell or non-clear cell renal cell carcinoma. Participants with collecting duct carcinoma histology are not eligible. Participants with multifocal or bilateral tumors are eligible
* STEP 1 REGISTRATION: Participants must have primary tumor in place
* STEP 1 REGISTRATION: Participants must have the following scans performed, showing clinical evidence of measurable or non-measurable metastatic disease:

  * Computed tomography (CT) scan of the chest (can be performed without contrast if CT contrast cannot be given)
  * CT of abdomen and pelvis with contrast OR magnetic resonance imaging (MRI) of the abdomen and pelvis with or without contrast

Scans must be performed within the following timeframes:

* Treatment naive participants must have scans documenting metastatic disease completed within 90 days prior to study registration
* Previously treated participants must have scans documenting metastatic disease completed within 90 days prior to first dose of systemic treatment

  * STEP 1 REGISTRATION: Participants with symptomatic metastases may have received palliative radiotherapy or receive palliative radiotherapy after registration
  * STEP 1 REGISTRATION: Participants must have no clear contraindications to nephrectomy
  * STEP 1 REGISTRATION: Participants must be offered the opportunity to participate in specimen bank. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
  * STEP 1 REGISTRATION: Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
  * STEP 1 REGISTRATION: As part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
  * STEP 2 REGISTRATION: Participants must have at least one of the following scans performed 12 weeks (+/- 2 weeks) after starting pre-randomization treatment
* CT scan of the chest (can be performed without contrast if CT contrast cannot be given)
* CT of abdomen and pelvis with contrast OR MRI of the abdomen and pelvis with or without contrast Scans must be performed within 28 days prior to randomization. Response should be assessed by comparing with a CT or MRI of the chest, abdomen and pelvis obtained prior to starting pre-randomization treatment. Participants with complete response in all metastatic sites are not eligible to randomize to Step 2

  • STEP 2 REGISTRATION: Participants must have one of the following objective statuses after 12 weeks of pre-randomization treatment
* Stable disease
* Partial response
* The treating investigator believes the patient is deriving clinical benefit from systemic therapy AND have Zubrod performance status 0-1

  * STEP 2 REGISTRATION: Participants must plan to continue the immune-based therapy received during pre-randomization treatment
  * STEP 2 REGISTRATION: Participants must be randomized on or between the 11th and 14th week of protocol-directed pre-randomization treatment therapy
  * STEP 2 REGISTRATION: Participants must have received at least one of the minimum amounts of immunotherapy:
* 2 infusions of nivolumab + 1 infusion of ipilimumab
* 2 infusions of pembrolizumab
* 2 infusions of avelumab

  * STEP 2 REGISTRATION: Participants must have a planned surgery date within 42 days of randomization
  * STEP 2 REGISTRATION: Participants must be a surgical candidate as determined by study urologist. The urology consult should be done within 42 days prior to randomization
  * STEP 2 REGISTRATION: Participants must have a complete physical examination and medical history within 28 days prior to randomization
  * STEP 2 REGISTRATION: Participants must have a Zubrod performance status of 0-1 within 28 days prior to randomization
  * STEP 2 REGISTRATION: Total bilirubin =\< institutional upper limit of normal (ULN) (within 28 days prior to randomization)
  * STEP 2 REGISTRATION: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3 x institutional upper limit of normal (ULN) (within 28 days prior to randomization)
  * STEP 2 REGISTRATION: Serum creatinine =\< 1.5 x the institutional upper limit of normal (IULN) OR measured OR calculated creatinine clearance \>= 50 mL/min using the Cockcroft-Gault Formula) (must have been drawn and processed within 28 days prior to randomization)

Exclusion Criteria:

* STEP 1 REGISTRATION: Participants must not have known active brain metastases. Participants with previously treated brain metastases are eligible if participant has no neurologic signs or symptoms suggestive of brain metastasis. Brain imaging studies are not required. If brain imaging studies are performed, they must be negative for disease
* STEP 1 REGISTRATION: Participants must not have received the following prior treatment of metastatic renal cell carcinoma:

  * Treatment naive participants must not have received any prior lines of systemic therapy for metastatic renal cell carcinoma beyond the line intended as part of protocol therapy
  * Previously treated participants must not have received any systemic therapy for metastatic renal cell carcinoma beyond the one regimen received off protocol as specified in Step 1 pre-randomization treatment
* STEP 1 REGISTRATION: Participants must not have received more than the following amounts protocol-directed pre-randomization treatment:

  * Treatment naive participants must not have received any pre-randomization treatment.
  * Previously treated participants must not be planning to receive any additional treatment prior to Step 2 randomization, and must not have received more than the following amounts of pre-randomization treatment:

    * 4 infusions of nivolumab
    * 4 infusions of ipilimumab
    * 4 infusions of pembrolizumab
    * 7 infusions of avelumab
* STEP 1 REGISTRATION: Participants must not have received immunotherapy for any cancer within the following timeframes:

  * Treatment naive participants must not have received any immunotherapy within a year of registration
  * Previously treated participants must not have received any other immunotherapy within a year of the start of off protocol specified pre-randomization treatment
* STEP 1 REGISTRATION: Participants must not have a solitary kidney and not have a transplanted kidney
* STEP 1 REGISTRATION: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, any in situ or T1 cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for at least two years
* STEP 1 REGISTRATION: Participants must not have been previously diagnosed with a medical condition that makes them ineligible for immune based combination therapy or nephrectomy
* STEP 2 REGISTRATION: Participants must not show progression in the primary tumor. Participants who are considered to have pseudo progression are allowed
* STEP 2 REGISTRATION: Participants must not have known active brain metastases. Participants with previously treated brain metastases are eligible if participant has no neurologic signs or symptoms suggestive of brain metastasis. Brain imaging studies are not required. If brain imaging studies are performed, they must be negative for disease
* STEP 2 REGISTRATION: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for two years

Where it's running

  • University of Alabama at Birmingham Cancer Center
    Birmingham, Alabama, United States
    Recruiting
  • Banner MD Anderson Cancer Center
    Gilbert, Arizona, United States
    Recruiting
  • Kingman Regional Medical Center
    Kingman, Arizona, United States
    Recruiting
  • Banner University Medical Center - Tucson
    Tucson, Arizona, United States
    Recruiting
  • University of Arizona Cancer Center-North Campus
    Tucson, Arizona, United States
    Recruiting
  • Mercy Hospital Fort Smith
    Fort Smith, Arkansas, United States
    Recruiting
Show 44 more locations
  • PCR Oncology
    Arroyo Grande, California, United States
    Recruiting
  • Sutter Auburn Faith Hospital
    Auburn, California, United States
    Recruiting
  • Sutter Cancer Centers Radiation Oncology Services-Auburn
    Auburn, California, United States
    Recruiting
  • Alta Bates Summit Medical Center-Herrick Campus
    Berkeley, California, United States
    Recruiting
  • Keck Medicine of USC Buena Park
    Buena Park, California, United States
    Recruiting
  • Sutter Cancer Centers Radiation Oncology Services-Cameron Park
    Cameron Park, California, United States
    Recruiting
  • Eden Hospital Medical Center
    Castro Valley, California, United States
    Recruiting
  • Sutter Davis Hospital
    Davis, California, United States
    Recruiting
  • City of Hope Comprehensive Cancer Center
    Duarte, California, United States
    Recruiting
  • Palo Alto Medical Foundation-Fremont
    Fremont, California, United States
    Recruiting
  • Keck Medicine of USC Huntington Beach
    Huntington Beach, California, United States
    Recruiting
  • Keck Medicine of USC Koreatown
    Los Angeles, California, United States
    Recruiting
  • Los Angeles County-USC Medical Center
    Los Angeles, California, United States
    Recruiting
  • USC / Norris Comprehensive Cancer Center
    Los Angeles, California, United States
    Recruiting
  • Cedars Sinai Medical Center
    Los Angeles, California, United States
    Recruiting
  • UCLA / Jonsson Comprehensive Cancer Center
    Los Angeles, California, United States
    Recruiting
  • Memorial Medical Center
    Modesto, California, United States
    Recruiting
  • Palo Alto Medical Foundation-Camino Division
    Mountain View, California, United States
    Recruiting
  • Palo Alto Medical Foundation-Gynecologic Oncology
    Mountain View, California, United States
    Recruiting
  • USC Norris Oncology/Hematology-Newport Beach
    Newport Beach, California, United States
    Recruiting
  • Sutter Cancer Research Consortium
    Novato, California, United States
    Recruiting
  • Palo Alto Medical Foundation Health Care
    Palo Alto, California, United States
    Recruiting
  • Keck Medical Center of USC Pasadena
    Pasadena, California, United States
    Recruiting
  • Sutter Cancer Centers Radiation Oncology Services-Roseville
    Roseville, California, United States
    Recruiting
  • Sutter Roseville Medical Center
    Roseville, California, United States
    Recruiting
  • Sutter Medical Center Sacramento
    Sacramento, California, United States
    Recruiting
  • University of California Davis Comprehensive Cancer Center
    Sacramento, California, United States
    Recruiting
  • California Pacific Medical Center-Pacific Campus
    San Francisco, California, United States
    Recruiting
  • Mills Health Center
    San Mateo, California, United States
    Recruiting
  • Palo Alto Medical Foundation-Santa Cruz
    Santa Cruz, California, United States
    Recruiting
  • Sutter Pacific Medical Foundation
    Santa Rosa, California, United States
    Recruiting
  • City of Hope South Pasadena
    South Pasadena, California, United States
    Recruiting
  • Palo Alto Medical Foundation-Sunnyvale
    Sunnyvale, California, United States
    Recruiting
  • Cedars-Sinai Cancer - Tarzana
    Tarzana, California, United States
    Recruiting
  • City of Hope Upland
    Upland, California, United States
    Recruiting
  • Sutter Cancer Centers Radiation Oncology Services-Vacaville
    Vacaville, California, United States
    Recruiting
  • Sutter Solano Medical Center/Cancer Center
    Vallejo, California, United States
    Recruiting
  • MedStar Washington Hospital Center
    Washington D.C., District of Columbia, United States
    Recruiting
  • AdventHealth Altamonte
    Altamonte Springs, Florida, United States
    Recruiting
  • AdventHealth Celebration
    Celebration, Florida, United States
    Recruiting
  • AdventHealth Kissimmee
    Kissimmee, Florida, United States
    Recruiting
  • AdventHealth Medical Group Urology at Orlando
    Orlando, Florida, United States
    Recruiting
  • AdventHealth Orlando
    Orlando, Florida, United States
    Recruiting
  • Orlando Health Cancer Institute
    Orlando, Florida, United States
    Recruiting

+337 more sites. See ClinicalTrials.gov for the full list.

Study contacts

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

How to take part

  1. Review the eligibility criteria above with your treating physician.
  2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
  3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.
Last reviewed 2026-11-14 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.