Active, not recruiting
Phase 3
A Study of Belzutifan (MK-6482) Versus Everolimus in Participants With Advanced Renal Cell Carcinoma (MK-6482-005)
Condition(s) studied
Carcinoma, Renal Cell
Investigational drug(s) / intervention(s)
BelzutifanEverolimus
Belzutifan: Oral tablets
Everolimus: Oral tablets
Study summary
The primary objective of this study is to compare belzutifan to everolimus with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR) and to compare everolimus with respect to overall survival (OS). The hypothesis is that belzutifan is superior to everolimus with respect to PFS and OS.
Eligibility
Inclusion Criteria:
* Has unresectable, locally advanced or metastatic clear cell renal cell carcinoma (RCC)
* Has had disease progression on or after having received systemic treatment for locally advanced or metastatic RCC with both Programmed cell death 1 ligand 1 (PD-1/L1) checkpoint inhibitor and a vascular endothelial growth factor - tyrosine kinase inhibitor (VEGF-TKI) in sequence or in combination
* Has received no more than 3 prior systemic regimens for locally advanced or metastatic RCC
* A male participant is eligible to participate if he is abstinent from heterosexual intercourse or agrees to use contraception during the intervention period and for at least 7 days after the last dose of study intervention
* A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a woman of childbearing potential (WOCBP) OR a WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 30 days after the last dose of study intervention for those randomized to belzutifan and for at least 8 weeks after the last dose of study intervention for those randomized to everolimus
* The participant (or legally acceptable representative if applicable) has provided documented informed consent for the study
* Has adequate organ function
Exclusion Criteria:
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. (Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ \[e.g., breast carcinoma, cervical cancer in situ\] that have undergone potentially curative therapy are not excluded)
* Has known central nervous system (CNS) metastases and/or carcinomatous meningitis. (Participants with previously treated brain metastases may participate provided they are radiologically stable for at least 4 weeks (28 days) by repeat imaging)
* Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study medication administration, or New York Heart Association Class III or IV congestive heart failure. (Medically controlled arrhythmia stable on medication is permitted)
* Has poorly controlled hypertension defined as systolic blood pressure (SBP) ≥150 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg
* Has moderate to severe hepatic impairment (Child-Pugh B or C)
* Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study
* Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption)
* Has known hypersensitivity or allergy to the active pharmaceutical ingredient or any component of the study intervention (belzutifan or everolimus) formulations
* Has received prior treatment with belzutifan or another hypoxia inducible factor 2α (HIF-2α inhibitor)
* Has received prior treatment with everolimus or any other specific or selective target of rapamycin complex 1 (TORC1)/ phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT) inhibitor (e.g., temsirolimus) in the advanced disease setting
* Has received any type of systemic anticancer antibody (including investigational antibody) within 4 weeks before randomization
* Has received prior radiotherapy within 2 weeks prior to randomization
* Has had major surgery within 3 weeks prior to randomization
* Has received a live vaccine within 30 days prior to randomization. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines are live attenuated vaccines and are not allowed
* Is currently receiving either strong (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of the study
* Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate (e.g., bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued for the duration of the study
* Is currently participating in a study of an investigational agent or is currently using an investigational device
* Has an active infection requiring systemic therapy
* Has active bacillus tuberculosis (TB)
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization
* Has a known history of human immunodeficiency virus (HIV) infection. (Testing for HIV at screening is only required if mandated by local health authority
* Has a known history of Hepatitis B virus (HBV) (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (HCV) (defined as HCV ribonucleic acid \[RNA\] \[qualitative\] is detected) infection
Primary outcome measure(s)
- Progression-free Survival (PFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) — Up to approximately 39 months
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review is presented here.
- Overall Survival (OS) — Up to approximately 49 months
OS is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.
Trial sites (172)
| Facility | City | Region | Status |
| Faculty Office Towers 1132 ( Site 1538) |
Birmingham |
Alabama |
|
| University of California San Diego Moores Cancer Center ( Site 1546) |
La Jolla |
California |
|
| St. Joseph Heritage Healthcare Local Lab ( Site 1531) |
Santa Rosa |
California |
|
| University of Colorado Cancer Center ( Site 1540) |
Aurora |
Colorado |
|
| UCHealth Highlands Ranch Hospital ( Site 1560) |
Highlands Ranch |
Colorado |
|
| Sibley Memorial Hospital ( Site 1559) |
Washington D.C. |
District of Columbia |
|
| Northwest Georgia Oncology Centers PC ( Site 1520) |
Marietta |
Georgia |
|
| The University of Chicago Medical Center ( Site 1539) |
Chicago |
Illinois |
|
| Ochsner Medical Center ( Site 1522) |
New Orleans |
Louisiana |
|
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 1514) |
Baltimore |
Maryland |
|
| Massachusetts General Hospital ( Site 1558) |
Boston |
Massachusetts |
|
| Beth Israel Deaconess Medical Center ( Site 1501) |
Boston |
Massachusetts |
|
| Dana Farber Cancer Institute ( Site 1505) |
Boston |
Massachusetts |
|
| Henry Ford Cancer Center ( Site 1511) |
Detroit |
Michigan |
|
| Hattiesburg Clinic ( Site 1509) |
Hattiesburg |
Mississippi |
|
| St. Vincent Frontier Cancer Center ( Site 1549) |
Billings |
Montana |
|
| John Theurer Cancer Center at Hackensack University Medical Center ( Site 1513) |
Hackensack |
New Jersey |
|
| University of Rochester Medical Center ( Site 1543) |
Rochester |
New York |
|
| University of North Carolina at Chapel Hill ( Site 1537) |
Chapel Hill |
North Carolina |
|
| Oncology Hematology Care, Inc. ( Site 1524) |
Cincinnati |
Ohio |
|
| Cleveland Clinic Main ( Site 1504) |
Cleveland |
Ohio |
|
| Oklahoma Cancer Specialists and Research Institute, LLC ( Site 1523) |
Tulsa |
Oklahoma |
|
| Oregon Health & Science University ( Site 1553) |
Portland |
Oregon |
|
| Abramson Cancer Center ( Site 1525) |
Philadelphia |
Pennsylvania |
|
| Fox Chase Cancer Center ( Site 1506) |
Philadelphia |
Pennsylvania |
|
| Medical University of South Carolina ( Site 1518) |
Charleston |
South Carolina |
|
| Henry Joyce Cancer Clinic ( Site 1544) |
Nashville |
Tennessee |
|
| Texas Oncology-Austin Central ( Site 1533) |
Austin |
Texas |
|
| Texas Oncology, P.A.-Dallas ( Site 1534) |
Dallas |
Texas |
|
| Centro Avançado de Tratamento Oncológico- CENANTRON ( Site 1657) |
Belo Horizonte |
Minas Gerais |
|
| Instituto de Cancer e Transplante de Curitiba ICTR ( Site 1650) |
Curitiba |
Paraná |
|
| Liga Norte Riograndense Contra o Cancer ( Site 1651) |
Natal |
Rio Grande do Norte |
|
| Hospital de Clinicas de Porto Alegre ( Site 1655) |
Porto Alegre |
Rio Grande do Sul |
|
| BP - A Beneficencia Portuguesa de São Paulo ( Site 1653) |
São Paulo |
São Paulo |
|
| BC Cancer - Vancouver Center ( Site 0155) |
Vancouver |
British Columbia |
|
| Nova Scotia Health Authority QEII-HSC ( Site 0150) |
Halifax |
Nova Scotia |
|
| Juravinski Cancer Centre ( Site 0154) |
Hamilton |
Ontario |
|
| Sunnybrook Research Institute ( Site 0153) |
Toronto |
Ontario |
|
| Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0151) |
Montreal |
Quebec |
|
| Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0152) |
Québec |
Quebec |
|
+ 132 more sites — see the full list on the official registry below.
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