The PROBE Trial: Immunotherapy With or Without Surgery for Metastatic Kidney Cancer
This study, called the PROBE Trial, is looking at how well immunotherapy-based drug combinations work for kidney cancer that has spread (metastatic kidney cancer). It compares two approaches: receiving the drug combination alone, or receiving the drug combination along with surgery to remove the kidney (nephrectomy). The immunotherapy drugs being studied include nivolumab, pembrolizumab, and avelumab, often combined with axitinib. These drugs help your immune system fight cancer cells. Doctors want to see if adding surgery improves how long people live. You might be able to join if you are 18 or older, have clear cell or non-clear cell metastatic kidney cancer, and your primary tumor is still in place. The study aims to enroll 364 participants and will track overall survival for up to 7 years.
- Study design
- This is an interventional study comparing two treatment approaches for metastatic kidney cancer. It plans to enroll 364 participants.
- What's involved
- You would receive immunotherapy drugs like nivolumab, pembrolizumab, or avelumab, potentially with axitinib. If assigned to surgery, it would be performed within 8 weeks of randomization.
- Compensation
- Not stated in the trial record.
- Follow-up
- Your overall survival will be assessed for up to 7 years after you join the study.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT04510597
Comparing the Outcome of Immunotherapy-Based Drug Combination Therapy With or Without Surgery to Remove the Kidney in Metastatic Kidney Cancer, the PROBE Trial
Recruiting
PHASE3Ages 18+InterventionalTreatmentSWOG Cancer Research NetworkGovernment-funded
~364 participants
Updated 2025-09-09 on ClinicalTrials.gov
What's tested:Cytoreductive NephrectomyActive Comparator
At a glance
Recruiting sites
340 of 387 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Overall survival
Measured over From date of randomization to date of death due to any cause, assessed up to 7 years.
Conditions
Where it's being run
387 sites across 33 statesIllinois64
Nevada45
California37
Ohio31
Wisconsin31
Michigan28
Minnesota25
Pennsylvania23
Who to contact
Opens a ready-to-send draft in your own email app — review before sending.
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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
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
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
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
What this trial measures
- Overall survivalFrom date of randomization to date of death due to any cause, assessed up to 7 years.
Analysis will be intent-to-treat. Evidence suggesting early termination of the trial and a conclusion that the cytoreductive nephrectomy (CN) approach is superior to treatment alone would be if the null hypothesis is rejected at the one-sided 0.005 level. For the second and third interim analyses, the null and alternative hypotheses with respect to survival will be tested, with superiority tested at the one-sided 0.005 level, and futility determined to be met if the (CN versus no CN) hazard ratio is greater than or equal to 1. A proportional hazards model will be fit to estimate the hazard ratio adjusting for the stratification factors as covariates in the model. Will evaluate whether each of the stratification factors are predictive factors of cytoreductive nephrectomy by placing an interaction term corresponding to each stratification factor and treatment arm in the proportional hazards survival model.