Belzutifan's Role in Active Surveillance Versus Treatment for Indolentmetastatic Clear Cell Renal Ccell Carcinoma (BRAVE-RCC)

NCT07023432 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2025-0268NCI-2025-04261
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

To learn if belzutifan can help to control the disease in patients with metastatic RCC who are considered candidates for active surveillance and have not undergone previous systemic treatment. The safety of belzutifan in this patient population will also be studied.

Conditions

Active Surveillance; Clear Cell Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Safety and adverse events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (2)

Treatment group

EXPERIMENTAL

Participants will take belzutifan by mouth every day during the study. You will be given a dosing diary to write down when you take each dose of belzutifan, including if you miss or vomit any doses. Bring the diary with you to each visit, along with any leftover study drug and/or study drug bottles.

Drug: Belzutifan

Observation group

EXPERIMENTAL

Participants will not receive treatment in this study. Instead, you will undergo active surveillance under the discretion of your treating physician.

Other: Active Surveillance

Interventions

Belzutifan DRUG

Given by PO

Treatment group

Active Surveillance OTHER

Given by Observation

Observation group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Metastatic clear cell renal cell carcinoma, with or without sarcomatoid features, clinically apparent less than 12 months.
• Male/female participants must be at least 18 years of age on the day of signing informed consent.
• IMDC risk score of 0 or 1.
• No prior systemic treatment for ccRCC. Adjuvant immunotherapy or targeted treatments allowed if progressive disease is noted at least 12 months after last dose of immunotherapy.
• Metastatic disease that is documented by imaging with CT or MRI and measurable by RECIST1.1.
• Participants must have signed and dated an Institutional Review Board (IRB)/Institutional Ethics Committee (IEC) approved written informed consent form (ICF) in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal participant care.
• Karnofsky performance status ≥ 70% and ECOG PS 0 or 1
• Suitable for active surveillance in the medical judgment of the treating oncologist.
• Participants must have adequate organ and marrow function as defined below:
• i. absolute neutrophil count ≥ 1.5 x 109/L ii. platelets ≥ 100 x 109/L iii. hemoglobin (Hgb) ≥ 9 g/dL iv. total bilirubin ≤ 1.5 x Institutional upper limit of normal (ULN) v. AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN vi. serum creatinine ≤ 1.5 × institutional ULN OR 24-hour clearance ≥ 40 mL/min
• \*Aspartate aminotransferase (serum glutamic-oxaloacetic transaminase)-AST(SCOT)/ Alanine aminotransferase (serum glutamic-pyruvic transaminase)- ALT(SGPT)
• A minimum of 28 days from any major surgery prior to registration.
• Ability to swallow, retain, and absorb oral medication.
• Baseline oxygen saturation \>92% on room air.
• Female Participants are eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:

You may not qualify if:

• Known or suspected brain metastases or active leptomeningeal disease.
• Requires any supplemental oxygen (either intermittent or chronic)
• Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with protocol
• Impairment of gastrointestinal function or disease that may significantly alter the absorption of belzutifan (e.g., uncontrolled nausea, vomiting, diarrhea, malabsorption syndromes, prior small bowel resection, or inflammatory bowel disease)
• Prior cardiovascular event including myocardial infarction, rest claudication, stroke, unstable angina, central nervous system (CNS) hemorrhage, unstable ventricular arrythmias, or severe congestive heart failure (NYHA Class 3 or higher) within the past 6 months
• Received colony-stimulating factors (eg, granulocyte colony stimulating factor, granulocytemacrophage colony stimulating factor or recombinant erythropoietin) ≤28 days prior to the first dose of study intervention.
• Has moderate to severe hepatic impairment (Child-Pugh B or C).
• Participants who have undergone major surgery ≤ 28 days prior to starting study drug, radiation ≤ 2 weeks prior to starting study drug, or who have not recovered from side effects of such therapy prior to registration.
• Has received any type of small molecule kinase inhibitor (including investigational agents) ≤2 weeks before randomization; any prior HIF-2a antagonist exposure.
• Has known hypersensitivity or allergy to the active pharmaceutical ingredient or any component of the study intervention (belzutifan) formulations.
• Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate (eg, bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued for the duration of the study.
• Active infection requiring systemic therapy within 14 days prior to treatment assignment.
• Has active tuberculosis.
• Active HBV (defined as HBsAg reactive and detectable HBV viral load) or active HCV (defined as HCV RNA \[qualitative\] is detected) infection.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

belzutifan; Watchful Waiting

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Study Officials

• Eric Jonasch, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eric Jonasch, MD

CONTACT

713-563-7232; ejonasch@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2025
• First Posted: June 17, 2025
• Study Start: December 3, 2025
• Primary Completion (Estimated): April 14, 2028
• Study Completion (Estimated): April 14, 2030
• Last Updated: June 17, 2025

Record last verified: 2025-06

Locations

US (1)