Clinical trial NCT04924075: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Pheochromocytoma/Paraganglioma
Pancreatic Neuroendocrine Tumor
Von Hippel-Lindau Disease
Advanced Gastrointestinal Stromal Tumor
HIF-2α Mutated Cancers
Keywords: HIF-2α
Pheochromocytoma/paraganglioma
Pancreatic NET
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2021-06-11
Enrollment: 322
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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: 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 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

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

Primary outcomes:
measure: Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR)
timeFrame: Up to approximately 5.5 years
Secondary outcomes:
measure: Duration of Response (DOR) as Assessed by BICR
timeFrame: Up to approximately 5.5 years
measure: Time to Response (TTR) as Assessed by BICR
timeFrame: Up to approximately 5.5 years
measure: Disease Control Rate (DCR) as Assessed by BICR
timeFrame: Up to approximately 5.5 years
measure: Progressive Free Survival (PFS) as Assessed by BICR
timeFrame: Up to approximately 5.5 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 5.5 years
measure: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: Up to approximately 5.5 years
measure: Number of Participants Discontinuing Study Drug due to an AE
timeFrame: Up to approximately 5.5 years
measure: Time to Surgery (TTS)
timeFrame: Up to approximately 5.5 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center ( Site 0110)
state: California
city: Chicago
country: United States
facility: Northwestern University - Robert H. Lurie Comprehensive Cancer Center ( Site 0130)
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa ( Site 0104)
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins Hospital-Sidney Kimmel Comprehensive Cancer Center - Developmental Therapeutics ( Site 0108)
state: Maryland
city: Bethesda
country: United States
facility: National Institutes of Health ( Site 0125)
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital ( Site 0111)
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan ( Site 0126)
state: Michigan
city: Saint Louis
country: United States
facility: Washington University-Internal Medicine/Oncology ( Site 0124)
state: Missouri
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai ( Site 0123)
state: New York
city: Philadelphia
country: United States
facility: Penn Medicine: University of Pennsylvania Health System-Heme/Onc ( Site 0127)
state: Pennsylvania
city: Nashville
country: United States
facility: SCRI Oncology Partners ( Site 7000)
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center ( Site 0107)
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center ( Site 0112)
state: Texas
city: Randwick
country: Australia
facility: Prince of Wales Hospital-Medical Oncology ( Site 1601)
state: New South Wales
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital ( Site 1602)
state: Victoria
city: Calgary
country: Canada
facility: Arthur J.E. Child Comprehensive Cancer Centre ( Site 0203)
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre ( Site 0202)
state: Ontario
city: Santiago
country: Chile
facility: FALP ( Site 2200)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Centro de Oncología de Precisión ( Site 2203)
state: Region M. De Santiago
city: Beijing
country: China
facility: Peking University First Hospital-Urology ( Site 1900)
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center ( Site 1905)
state: Guangdong
city: Shanghai
country: China
facility: Renji Hospital Shanghai Jiao Tong University School of Medicine ( Site 1904)
state: Shanghai
city: Cheng Du
country: China
facility: West China Hospital of Sichuan University ( Site 1906)
state: Sichuan
city: Copenhagen
country: Denmark
facility: Rigshospitalet ( Site 0304)
state: Hovedstaden
city: Copenhagen
country: Denmark
facility: Rigshospitalet-Department of Endocrinology ( Site 0303)
state: Hovedstaden
city: Odense C
country: Denmark
facility: Odense Universitetshospital ( Site 0302)
state: Syddanmark
city: Strasbourg
country: France
facility: CHU Strasbourg-Hautepierre-Medecine Interne, Endocrinologie et Nutrition ( Site 0402)
state: Alsace
city: Marseille
country: France
facility: Institut Paoli-Calmettes-Oncology ( Site 0406)
state: Bouches-du-Rhone
city: Villejuif
country: France
facility: Gustave Roussy ( Site 0403)
state: Ile-de-France
city: Le Kremlin-Bicêtre
country: France
facility: Hôpitaux Universitaires Paris Sud - Hôpital Bicêtre ( Site 0407)
state: Paris
city: Lyon
country: France
facility: Hôpital Edouard Herriot-oncologie ( Site 0405)
state: Rhone-Alpes
city: Paris
country: France
facility: Hopitaux Universitaires Paris Centre-Hopital Cochin ( Site 0404)
city: München
country: Germany
facility: Klinikum der Ludwig-Maximilians-Universitaet Muenchen-Department of Internal Medicine IV, Division ( Site 0501)
state: Bayern
city: Würzburg
country: Germany
facility: Comprehensive Cancer Center Mainfranken-Div. of Endocrinology and Diabetes ( Site 0500)
state: Bayern
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg ( Site 0504)
state: Brandenburg
city: Düsseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf-Gastroenterology, Hepatology and Infectiology ( Site 0505)
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Charité Universitaetsmedizin Berlin - Campus Mitte-Department of Endocrinology and Metabolism ( Site 0503)
city: Budapest
country: Hungary
facility: Semmelweis University-Belgyógyászati és Onkológiai Klinika Hematológia Osztály ( Site 0600)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center-Institute of Endocrinology, Diabetes and Metabolism ( Site 1400)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 1401)
city: Naples
country: Italy
facility: University of Naples Federico II-Dipartimento di Medicina Clinica e Chirurgia ( Site 0704)
state: Campania
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola ( Site 0708)
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia-Oncology ( Site 0701)
city: Milano
country: Italy
facility: Ospedale San Raffaele-Oncologia Medica ( Site 0705)
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia IRCCS-Divisione di Oncologia Medica Gastrointestinale e Tumori Neuroe ( Site 0700)
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma ( Site 0703)
city: Sapporo
country: Japan
facility: Hokkaido University Hospital ( Site 1800)
state: Hokkaido
city: Yokohama-shi
country: Japan
facility: Yokohama City University Hospital ( Site 1804)
state: Kanagawa
city: Nankoku
country: Japan
facility: Kochi Medical School Hospital ( Site 1807)
state: Kochi
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital ( Site 1802)
state: Tokyo
city: Kyoto
country: Japan
facility: Kyoto University Hospital ( Site 1806)
city: Tokyo
country: Japan
facility: Tokyo Women's Medical University Adachi Medical Center ( Site 1803)
city: Jongno-gu
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 2001)
state: Seoul
city: Songpa-gu
country: Korea, Republic of
facility: Asan Medical Center ( Site 2000)
state: Seoul
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht ( Site 1530)
city: Oslo
country: Norway
facility: Oslo Universitetssykehus Radiumhospitalet ( Site 2400)
city: Ufa
country: Russian Federation
facility: GBUZ Republican Clinical Oncological Dispensary ( Site 0804)
state: Baskortostan, Respublika
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg State University-Clinic of advanced medical technologies n. a. Nicolay I. Pirogov ( Site 0805)
state: Leningradskaya Oblast
city: Saint Petersburg
country: Russian Federation
facility: Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 0803)
state: Leningradskaya Oblast
city: Moscow
country: Russian Federation
facility: Fed State Budgetary Inst N.N. Blokhin Med Center of Oncology MHRF ( Site 0801)
state: Moskva
city: Moscow
country: Russian Federation
facility: Endocrinology Research Center of Rosmedtechnologies-Surgery ( Site 0809)
state: Moskva
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore ( Site 1700)
state: Central Singapore
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias-Medical Oncology ( Site 1101)
state: Asturias
city: Madrid
country: Spain
facility: MD Anderson Cancer Center-Oncology ( Site 1102)
state: Madrid, Comunidad De
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre-Medical Oncology ( Site 1103)
state: Madrid, Comunidad De
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron ( Site 1100)
city: Lund
country: Sweden
facility: Skanes University Hospital Lund ( Site 1200)
state: Skane Lan
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Solna ( Site 1202)
state: Stockholms Lan
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset-Blod- och tumörsjukdomar ( Site 1201)
state: Uppsala Lan
city: Gothenburg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset-Department of Oncology CTU Clinical Trial Unit ( Site 1204)
state: Vastra Gotalands Lan
city: Yuregir
country: Turkey
facility: Baskent University Adana Training Hospital ( Site 0906)
state: Adana
city: Bornova
country: Turkey
facility: Ege University Medicine of Faculty ( Site 0900)
state: Izmir
city: Ankara
country: Turkey
facility: Hacettepe Universitesi-oncology hospital ( Site 0901)
city: Ankara
country: Turkey
facility: Ankara Bilkent Şehir Hastanesi. ( Site 0904)
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 0902)
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital ( Site 1309)
state: Cambridgeshire
city: London
country: United Kingdom
facility: Royal Free Hospital ( Site 1302)
state: England
city: Glasgow
country: United Kingdom
facility: The Beatson West of Scotland Cancer Centre ( Site 1308)
state: Glasgow City
city: London
country: United Kingdom
facility: Hammersmith Hospital-Medical Oncology ( Site 1304)
state: London, City Of
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: