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NCT04924075PHASE2Recruiting

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)

Merck Sharp & Dohme LLC

Start Date

8/12/2021

Completion Date

12/27/2029

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 Criteria

Age Range: 12 years to No maximum

The main inclusion criteria include but are not limited to the following: * 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 B1: 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 The main exclusion criteria include but are not limited to the following: * 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

DRUG

Belzutifan

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Conditions

Pheochromocytoma/ParagangliomaPancreatic Neuroendocrine TumorVon Hippel-Lindau DiseaseAdvanced Gastrointestinal Stromal TumorHIF-2α Mutated Cancers

Locations

Cedars-Sinai Medical Center ( Site 0110)

Los Angeles, California 90048

United States

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

Chicago, Illinois 60611

United States

Northwestern Medicine Cancer Center - Warrenville ( Site 0134)

Warrenville, Illinois 60555

United States

University of Iowa ( Site 0104)

Iowa City, Iowa 52242

United States

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

Baltimore, Maryland 21287

United States

National Institutes of Health ( Site 0125)

Bethesda, Maryland 20892

United States

Massachusetts General Hospital ( Site 0111)

Boston, Massachusetts 02114

United States

University of Michigan ( Site 0126)

Ann Arbor, Michigan 48109

United States

Washington University-Internal Medicine/Oncology ( Site 0124)

St Louis, Missouri 63110

United States

Icahn School of Medicine at Mount Sinai ( Site 0123)

New York, New York 10029

United States

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

Philadelphia, Pennsylvania 19104

United States

SCRI Oncology Partners ( Site 7000)

Nashville, Tennessee 37203

United States

Vanderbilt University Medical Center ( Site 0107)

Nashville, Tennessee 37232

United States

University of Texas MD Anderson Cancer Center ( Site 0112)

Houston, Texas 77030

United States

Prince of Wales Hospital-Medical Oncology ( Site 1601)

Randwick, New South Wales 2031

Australia

The Royal Melbourne Hospital ( Site 1602)

Parkville, Victoria 3050

Australia

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

Calgary, Alberta T2N 5G2

Canada

Princess Margaret Cancer Centre ( Site 0202)

Toronto, Ontario M5G 2M9

Canada

FALP ( Site 2200)

Santiago, Region M. de Santiago 7500921

Chile

Centro de Oncología de Precisión ( Site 2203)

Santiago, Region M. de Santiago 7560908

Chile

Peking University First Hospital-Urology ( Site 1900)

Beijing, Beijing Municipality 100034

China

Sun Yat-sen University Cancer Center ( Site 1905)

Guangzhou, Guangdong 510060

China

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

Shanghai, Shanghai Municipality 200001

China

West China Hospital of Sichuan University ( Site 1906)

Chengdu, Sichuan 610041

China

Rigshospitalet ( Site 0304)

Copenhagen, Capital Region 2100

Denmark

Rigshospitalet-Department of Endocrinology ( Site 0303)

Copenhagen, Capital Region 2100

Denmark

Odense Universitetshospital ( Site 0302)

Odense, Region Syddanmark 5000

Denmark

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

Strasbourg, Alsace 67098

France

Hôpital Edouard Herriot-oncologie ( Site 0405)

Lyon, Auvergne-Rhône-Alpes 69003

France

Institut Paoli-Calmettes-Oncology ( Site 0406)

Marseille, Bouches-du-Rhone 13009

France

Hôpitaux Universitaires Paris Sud - Hôpital Bicêtre ( Site 0407)

Le Kremlin-Bicêtre, Paris 94270

France

Hopitaux Universitaires Paris Centre-Hopital Cochin ( Site 0404)

Paris, 75014

France

Gustave Roussy ( Site 0403)

Villejuif, Île-de-France Region 94805

France

Universitaetsklinikum Freiburg ( Site 0504)

Freiburg im Breisgau, Baden-Wurttemberg 79106

Germany

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

München, Bavaria 80336

Germany

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

Würzburg, Bavaria 97080

Germany

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

Düsseldorf, North Rhine-Westphalia 40225

Germany

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

Berlin, 10117

Germany

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

Budapest, 1083

Hungary

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

Ramat Gan, 5262100

Israel

Sourasky Medical Center ( Site 1401)

Tel Aviv, 6423906

Israel

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

Naples, Campania 80100

Italy

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

Milan, Lombardy 20133

Italy

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

Siena, Tuscany 53100

Italy

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

Bologna, 40138

Italy

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

Brescia, 25123

Italy

Ospedale San Raffaele-Oncologia Medica ( Site 0705)

Milan, 20132

Italy

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

Milan, 20141

Italy

Centro Ricerche Cliniche di Verona ( Site 0703)

Verona, 37134

Italy

Hokkaido University Hospital ( Site 1800)

Sapporo, Hokkaido 060-8648

Japan

Yokohama City University Hospital ( Site 1804)

Yokohama, Kanagawa 236-0004

Japan

Kochi Medical School Hospital ( Site 1807)

Nankoku, Kochi 783-8505

Japan

National Cancer Center Hospital ( Site 1802)

Chuo-ku, Tokyo 104-0045

Japan

Kyoto University Hospital ( Site 1806)

Kyoto, 606-8507

Japan

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

Tokyo, 123-8558

Japan

Universitair Medisch Centrum Utrecht ( Site 1530)

Utrecht, 3584 CX

Netherlands

Oslo Universitetssykehus Radiumhospitalet ( Site 2400)

Oslo, 0424

Norway

START Lisbon - Hospital de Santa Maria ( Site 2601)

Lisbon, Lisbon District 1649-035

Portugal

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

Porto, 4200-072

Portugal

GBUZ Republican Clinical Oncological Dispensary ( Site 0804)

Ufa, Baskortostan, Respublika 450054

Russia

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

Saint Petersburg, Leningradskaya Oblast' 190020

Russia

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

Saint Petersburg, Leningradskaya Oblast' 198255

Russia

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

Moscow, Moscow 115522

Russia

Endocrinology Research Center of Rosmedtechnologies-Surgery ( Site 0809)

Moscow, Moscow 117036

Russia

National Cancer Centre Singapore ( Site 1700)

Singapore, Central Singapore 168583

Singapore

Seoul National University Hospital ( Site 2001)

Jongno-gu, Seoul 03080

South Korea

Asan Medical Center ( Site 2000)

Songpa-gu, Seoul 05505

South Korea

MD Anderson Cancer Center-Oncology ( Site 1102)

Madrid, Madrid, Comunidad de 28033

Spain

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

Madrid, Madrid, Comunidad de 28041

Spain

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

Oviedo, Principality of Asturias 33011

Spain

Hospital Universitari Vall d'Hebron ( Site 1100)

Barcelona, 08035

Spain

Skanes University Hospital Lund ( Site 1200)

Lund, Skåne County 221 85

Sweden

Karolinska Universitetssjukhuset Solna ( Site 1202)

Stockholm, Stockholm County 171 76

Sweden

Akademiska sjukhuset-Blod- och tumörsjukdomar ( Site 1201)

Uppsala, Uppsala County 751 85

Sweden

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

Gothenburg, Västra Götaland County 413 45

Sweden

Baskent University Adana Training Hospital ( Site 0906)

Yüreğir, Adana 01250

Turkey (Türkiye)

Ege University Medicine of Faculty ( Site 0900)

Bornova, İzmir 35100

Turkey (Türkiye)

Hacettepe Universitesi-oncology hospital ( Site 0901)

Ankara, 06230

Turkey (Türkiye)

Ankara Bilkent Şehir Hastanesi. ( Site 0904)

Ankara, 06800

Turkey (Türkiye)

Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 0902)

Istanbul, 34668

Turkey (Türkiye)

Addenbrooke's Hospital ( Site 1309)

Cambridge, Cambridgeshire CB2 2QQ

United Kingdom

Royal Free Hospital ( Site 1302)

London, England NW3 2QG

United Kingdom

The Beatson West of Scotland Cancer Centre ( Site 1308)

Glasgow, Glasgow City G12 0YN

United Kingdom

Hammersmith Hospital-Medical Oncology ( Site 1304)

London, London, City of W12 OHS

United Kingdom