Belzutifan's Role in Active Surveillance Versus Treatment for Indolentmetastatic Clear Cell Renal Ccell Carcinoma (BRAVE-RCC)
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.
• 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:
∙ Is not a woman of child-bearing potential (WOCBP) OR
‣ Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 30 days after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
‣ A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention.
‣ If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
‣ The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
‣ Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
⁃ Male participants are eligible to participate if they agree to the following during the intervention period and for at least 7 days after the last dose of study intervention:
∙ Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR
‣ Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause as detailed below:
⁃ Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
• Male participants must also agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person of any sex.
‣ Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
⁃ Participants 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.