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Protocol Details

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

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

001715-C

Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 12 Years
Max Age: 120 Years

Referral Letter Required

No

Population Exclusion(s)

Fetuses;
Pregnant Women;
Neonates

Keywords

HIF-2 alpha;
Pheochromocytoma/paraganglioma;
Pancreatic NET;
Gastrointestinal Stromal Tumor

Recruitment Keyword(s)

None

Condition(s)

Neuroectodermal Tumors;
Neoplasms, Germ Cell and Embryonal;
Neoplasms by Histologic Type;
Neoplasms, Nerve Tissue;
Neoplasms, Connective Tissue;
Neoplasms, Connective and Soft Tissue;
Gastrointestinal Neoplasms;
Digestive System Neoplasms;
Digestive System Diseases;
Gastrointestinal Diseases;
Adenoma;
Neoplasms, Glandular and Epithelial;
Pancreatic Neoplasms;
Neoplasms by Site;
Endocrine Gland Neoplasms

Investigational Drug(s)

Belzutifan

Investigational Device(s)

None

Intervention(s)

Drug: Belzutifan

Supporting Site

National Cancer Institute

Background:

Pheochromocytomas and paraganglioma (PPGLs) are rare tumors of the adrenal glands and related nerves. About 2 to 8 people per million are diagnosed with PPGLs in the US each year. Between 15% and 20% of these tumors are cancerous.

SDH-deficient gastrointestinal stromal tumor, also known as SDH-deficient GIST, is a form of gastrointestinal malignancy that primarily affects the stomach or small intestine, with less common occurrences in the large intestine. Approximately 5% to 7.5% of GISTs are classified as "SDH-deficient" and primarily manifest in the stomach. SDH refers to succinate dehydrogenase, a critical protein involved in energy production within the body. SDH-deficient GISTs are predominantly observed in pediatric patients and certain young adults.

HIF-2-alpha serves as a crucial modulator of the cellular oxygen-signaling cascade. It plays a role in upregulating genes associated with cell growth, metastasis, and tumor progression. Activation of HIF-1-alpha has been closely linked with various types of malignancies.

Researchers want to know if an FDA-approved drug called belzutifan can help treat PPGLs, SDH-deficient GIST, HIF-2-alpha related-cancers.

Objective:

To test a drug (belzutifan) in people with PPGLs, GIST and HIF-2-alpha related-cancers.

Eligibility:

People aged 12 years and older with PPGLs, GIST and HIF-2-alpha related-cancers, and related cancers that have not responded to treatment.

Design:

Participants will be screened. They will have a physical exam, imaging scans, and blood tests. They will have tests of their heart function. Small pieces of tumor tissue will be collected. They will have a bone scan and an eye exam.

Belzutifan is a pill taken by mouth. Participants will take the drug at home once a day. They will write down their doses in a diary. They may also track their blood pressure at home.

Participants will visit the clinic 9 times in their first 6 months. Then they will have clinic visits every 4 weeks. Imaging scans, blood tests, and other tests will be repeated during the study. Some blood may be used for genetic testing.

Participants may remain in the study as long as the drug is helping them. If they stop taking the drug, they will have a follow-up visit after 4 weeks. Follow-up visits will continue every 8 to 12 weeks.

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Eligibility

INCLUSION CRITERIA:

Adults and adolescents >=12 years of age and weighing >=40 kg (cohort specific exceptions noted below) with one of the following indications:

- Advanced (unresectable and/or metastatic) PPGL (Cohort A1): Adult and adolescent

- Advanced pNET who have progressed on or after at least one prior systemic therapy, which includes an approved targeted agent (such as sunitinib or everolimus) (Cohort A2): Adult and adolescent

- VHL disease-associated localized tumors (Cohort B1): Adult only - Advanced wt GIST (Cohort C): Adult and adolescent

- Advanced solid tumors with HIF-2alpha related genetic alterations (Cohort D): Adult and adolescent


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Citations:

Not Provided

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Contacts:

Principal Investigator

Referral Contact

For more information:

Jaydira Del Rivero, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CLINICAL CENTER BG RM 13C434
10 CENTER DR
BETHESDA MD 20892
(240) 858-3851
delriveroj@mail.nih.gov

Kimberley J. Cooper
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 8D44
10 Center Drive
Bethesda, Maryland 20892
(240) 858-7989
kimberley.cooper@nih.gov

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
1-888-NCI-1937
ncimo_referrals@mail.nih.gov

Clinical Trials Number:

NCT04924075

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