RecruitingPhase 2NCT04924075

Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL) Disease-Associated Tumors, Advanced Gastrointestinal Stromal Tumor (wt GIST), or Solid Tumors With HIF-2α Related Genetic Alterations (MK-6482-015)

A Phase 2 Study to Evaluate the Efficacy and Safety of Belzutifan (MK-6482, Formerly PT2977) Monotherapy in Participants With Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL) Disease-Associated Tumors, Advanced Gastrointestinal Stromal Tumor (wt GIST), or Advanced Solid Tumors With HIF-2α Related Genetic Alterations


Sponsor

Merck Sharp & Dohme LLC

Enrollment

322 participants

Start Date

Aug 12, 2021

Study Type

INTERVENTIONAL

Conditions

Summary

This is a study to evaluate the efficacy and safety of belzutifan monotherapy in participants with advanced pheochromocytoma/paraganglioma (PPGL), pancreatic neuroendocrine tumor (pNET), von Hippel-Lindau (VHL) disease-associated tumors, advanced wt (wild-type) gastrointestinal stromal tumor (wt GIST), or advanced solid tumors with hypoxia inducible factor-2 alpha (HIF-2α) related genetic alterations. The primary objective of the study is to evaluate the objective response rate (ORR) of belzutifan per response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) by blinded independent central review (BICR).


Eligibility

Min Age: 12 Years

Inclusion Criteria6

  • Male and female participants at least 12 years of age (at least 18 years of age for Cohort B1)
  • Diagnosis of one of the following: Advanced/metastatic pheochromocytoma/paraganglioma (PPGL), pancreatic neuroendocrine tumors (pNET), von Hippel-Lindau (VHL) disease associated localized tumors, or advanced wild-type gastrointestinal stromal tumor (wt GIST) or advanced solid tumors with Hypoxia Inducible Factor- 2 alpha subunit (HIF-2α) related genetic alterations
  • Cohort BI: VHL Disease-associated tumors:
  • Have a diagnosis of VHL disease as determined by a germline test locally and/or clinical diagnosis
  • Must be ≥18 years of age
  • Has a life expectancy of at least 3 months

Exclusion Criteria5

  • Unable to swallow orally administered medication or has a disorder that might affect the absorption of belzutifan
  • History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
  • Any of the following: A pulse oximeter reading \<92% at rest, or requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
  • Clinically significant cardiac disease, including unstable angina, acute myocardial infarction, or arterial bypass (CABG) or Percutaneous transluminal coronary angioplasty (PTCA) ≤6 months from study entry, or New York Heart Association Class III or IV congestive heart failure
  • Received prior treatment (except somatostatin analogs) with chemotherapy, targeted therapy, biologics, or other investigational therapy within the past 4 weeks of first dose of study intervention

Interventions

DRUGBelzutifan

Belzutifan, 120 mg, oral, once daily (QD) until progressive disease or discontinuation.


Locations(84)

Cedars-Sinai Medical Center ( Site 0110)

Los Angeles, California, United States

Northwestern University - Robert H. Lurie Comprehensive Cancer Center ( Site 0130)

Chicago, Illinois, United States

Northwestern Medicine Cancer Center - Warrenville ( Site 0134)

Warrenville, Illinois, United States

University of Iowa ( Site 0104)

Iowa City, Iowa, United States

Johns Hopkins Hospital-Sidney Kimmel Comprehensive Cancer Center - Developmental Therapeutics ( Site 0108)

Baltimore, Maryland, United States

National Institutes of Health ( Site 0125)

Bethesda, Maryland, United States

Massachusetts General Hospital ( Site 0111)

Boston, Massachusetts, United States

University of Michigan ( Site 0126)

Ann Arbor, Michigan, United States

Washington University-Internal Medicine/Oncology ( Site 0124)

St Louis, Missouri, United States

Icahn School of Medicine at Mount Sinai ( Site 0123)

New York, New York, United States

Penn Medicine: University of Pennsylvania Health System-Heme/Onc ( Site 0127)

Philadelphia, Pennsylvania, United States

SCRI Oncology Partners ( Site 7000)

Nashville, Tennessee, United States

Vanderbilt University Medical Center ( Site 0107)

Nashville, Tennessee, United States

University of Texas MD Anderson Cancer Center ( Site 0112)

Houston, Texas, United States

Prince of Wales Hospital-Medical Oncology ( Site 1601)

Randwick, New South Wales, Australia

The Royal Melbourne Hospital ( Site 1602)

Parkville, Victoria, Australia

Arthur J.E. Child Comprehensive Cancer Centre ( Site 0203)

Calgary, Alberta, Canada

Princess Margaret Cancer Centre ( Site 0202)

Toronto, Ontario, Canada

FALP ( Site 2200)

Santiago, Region M. de Santiago, Chile

Centro de Oncología de Precisión ( Site 2203)

Santiago, Region M. de Santiago, Chile

Peking University First Hospital-Urology ( Site 1900)

Beijing, Beijing Municipality, China

Sun Yat-sen University Cancer Center ( Site 1905)

Guangzhou, Guangdong, China

Renji Hospital Shanghai Jiao Tong University School of Medicine ( Site 1904)

Shanghai, Shanghai Municipality, China

West China Hospital of Sichuan University ( Site 1906)

Chengdu, Sichuan, China

Rigshospitalet ( Site 0304)

Copenhagen, Capital Region, Denmark

Rigshospitalet-Department of Endocrinology ( Site 0303)

Copenhagen, Capital Region, Denmark

Odense Universitetshospital ( Site 0302)

Odense, Region Syddanmark, Denmark

CHU Strasbourg-Hautepierre-Medecine Interne, Endocrinologie et Nutrition ( Site 0402)

Strasbourg, Alsace, France

Hôpital Edouard Herriot-oncologie ( Site 0405)

Lyon, Auvergne-Rhône-Alpes, France

Institut Paoli-Calmettes-Oncology ( Site 0406)

Marseille, Bouches-du-Rhone, France

Hôpitaux Universitaires Paris Sud - Hôpital Bicêtre ( Site 0407)

Le Kremlin-Bicêtre, Paris, France

Hopitaux Universitaires Paris Centre-Hopital Cochin ( Site 0404)

Paris, France

Gustave Roussy ( Site 0403)

Villejuif, Île-de-France Region, France

Klinikum der Ludwig-Maximilians-Universitaet Muenchen-Department of Internal Medicine IV, Division ( Site 0501)

München, Bavaria, Germany

Comprehensive Cancer Center Mainfranken-Div. of Endocrinology and Diabetes ( Site 0500)

Würzburg, Bavaria, Germany

Universitaetsklinikum Freiburg ( Site 0504)

Freiburg, Brandenburg, Germany

Universitaetsklinikum Duesseldorf-Gastroenterology, Hepatology and Infectiology ( Site 0505)

Düsseldorf, North Rhine-Westphalia, Germany

Charité Universitaetsmedizin Berlin - Campus Mitte-Department of Endocrinology and Metabolism ( Site 0503)

Berlin, Germany

Semmelweis University-Belgyógyászati és Onkológiai Klinika Hematológia Osztály ( Site 0600)

Budapest, Hungary

Sheba Medical Center-Institute of Endocrinology, Diabetes and Metabolism ( Site 1400)

Ramat Gan, Israel

Sourasky Medical Center ( Site 1401)

Tel Aviv, Israel

University of Naples Federico II-Dipartimento di Medicina Clinica e Chirurgia ( Site 0704)

Naples, Campania, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori-S.C. Oncologia Medica 2- Sarcomi ( Site 0709)

Milan, Lombardy, Italy

Azienda Ospedaliero Universitaria Senese-U.O.C. Immunoterapia Oncologica ( Site 0706)

Siena, Tuscany, Italy

IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola ( Site 0708)

Bologna, Italy

Azienda Ospedaliera Spedali Civili di Brescia-Oncology ( Site 0701)

Brescia, Italy

Ospedale San Raffaele-Oncologia Medica ( Site 0705)

Milan, Italy

Istituto Europeo di Oncologia IRCCS-Divisione di Oncologia Medica Gastrointestinale e Tumori Neuroe ( Site 0700)

Milan, Italy

Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma ( Site 0703)

Verona, Italy

Hokkaido University Hospital ( Site 1800)

Sapporo, Hokkaido, Japan

Yokohama City University Hospital ( Site 1804)

Yokohama, Kanagawa, Japan

Kochi Medical School Hospital ( Site 1807)

Nankoku, Kochi, Japan

National Cancer Center Hospital ( Site 1802)

Chuo-ku, Tokyo, Japan

Kyoto University Hospital ( Site 1806)

Kyoto, Japan

Tokyo Women's Medical University Adachi Medical Center ( Site 1803)

Tokyo, Japan

Universitair Medisch Centrum Utrecht ( Site 1530)

Utrecht, Netherlands

Oslo Universitetssykehus Radiumhospitalet ( Site 2400)

Oslo, Norway

START Lisbon - Hospital de Santa Maria ( Site 2601)

Lisbon, Lisbon District, Portugal

Instituto Portugues de Oncologia Do Porto Francisco Gentil E.P.E. ( Site 2600)

Porto, Portugal

GBUZ Republican Clinical Oncological Dispensary ( Site 0804)

Ufa, Baskortostan, Respublika, Russia

Saint Petersburg State University-Clinic of advanced medical technologies n. a. Nicolay I. Pirogov ( Site 0805)

Saint Petersburg, Leningradskaya Oblast', Russia

Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 0803)

Saint Petersburg, Leningradskaya Oblast', Russia

Fed State Budgetary Inst N.N. Blokhin Med Center of Oncology MHRF ( Site 0801)

Moscow, Moscow, Russia

Endocrinology Research Center of Rosmedtechnologies-Surgery ( Site 0809)

Moscow, Moscow, Russia

National Cancer Centre Singapore ( Site 1700)

Singapore, Central Singapore, Singapore

Seoul National University Hospital ( Site 2001)

Jongno-gu, Seoul, South Korea

Asan Medical Center ( Site 2000)

Songpa-gu, Seoul, South Korea

MD Anderson Cancer Center-Oncology ( Site 1102)

Madrid, Madrid, Comunidad de, Spain

Hospital Universitario 12 de Octubre-Medical Oncology ( Site 1103)

Madrid, Madrid, Comunidad de, Spain

Hospital Universitario Central de Asturias-Medical Oncology ( Site 1101)

Oviedo, Principality of Asturias, Spain

Hospital Universitari Vall d'Hebron ( Site 1100)

Barcelona, Spain

Skanes University Hospital Lund ( Site 1200)

Lund, Skåne County, Sweden

Karolinska Universitetssjukhuset Solna ( Site 1202)

Stockholm, Stockholm County, Sweden

Akademiska sjukhuset-Blod- och tumörsjukdomar ( Site 1201)

Uppsala, Uppsala County, Sweden

Sahlgrenska Universitetssjukhuset-Department of Oncology CTU Clinical Trial Unit ( Site 1204)

Gothenburg, Västra Götaland County, Sweden

Baskent University Adana Training Hospital ( Site 0906)

Yüreğir, Adana, Turkey (Türkiye)

Ege University Medicine of Faculty ( Site 0900)

Bornova, İzmir, Turkey (Türkiye)

Hacettepe Universitesi-oncology hospital ( Site 0901)

Ankara, Turkey (Türkiye)

Ankara Bilkent Şehir Hastanesi. ( Site 0904)

Ankara, Turkey (Türkiye)

Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 0902)

Istanbul, Turkey (Türkiye)

Addenbrooke's Hospital ( Site 1309)

Cambridge, Cambridgeshire, United Kingdom

Royal Free Hospital ( Site 1302)

London, England, United Kingdom

The Beatson West of Scotland Cancer Centre ( Site 1308)

Glasgow, Glasgow City, United Kingdom

Hammersmith Hospital-Medical Oncology ( Site 1304)

London, London, City of, United Kingdom

View Full Details on ClinicalTrials.gov

For the most up-to-date information, visit the official listing.

Visit

NCT04924075


Related Trials