What side effects are associated with this type of intervention?

Common treatments for Pancreatic Neuroendocrine Tumors (pNETs) include HIF-2α inhibitors like Belzutifan, mTOR inhibitors like everolimus, and tyrosine kinase inhibitors like sunitinib. The known side effects of these treatments can include fatigue, anemia, hyperglycemia, decreased appetite, nausea, and diarrhea. Additionally, everolimus may cause stomatitis, infections, and non-infectious pneumonitis, while sunitinib can lead to hypertension, hand-foot syndrome, and gastrointestinal disturbances. It is important for patients to discuss these potential side effects with their healthcare provider to manage them effectively.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Pancreatic Neuroendocrine Tumors (pNETs). Notably, everolimus (an mTOR inhibitor) and sunitinib (a tyrosine kinase inhibitor) have been approved for advanced pNETs. These drugs target pathways involved in tumor growth and angiogenesis, similar to the mechanism of action of HIF-2α inhibitors like Belzutifan, which is currently under study. Additionally, somatostatin analogs such as octreotide and lanreotide are used to manage symptoms and control tumor growth in pNETs.

What other types of research exist?

Promising alternatives to Belzutifan for Pancreatic Neuroendocrine Tumors include Everolimus (an mTOR inhibitor), Sunitinib (a multityrosine kinase inhibitor), and Peptide Receptor Radionuclide Therapy (PRRT) using radiolabeled somatostatin analogs such as Lutetium Lu-177 Dotatate. These treatments have shown efficacy in extending progression-free survival and controlling tumor growth in clinical studies.

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HIF-2α Inhibitor

Belzutifan for Advanced Cancers

Phase 2

Recruiting

Research Sponsored by Merck Sharp & Dohme Corp.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Cohort A1: Pheochromocytoma/Paraganglioma (PPGL) - Has documented histopathological diagnosis of pheochromocytoma or paraganglioma

Cohort D participants with advanced solid tumors with HIF-2α related genetic alterations - Has locally advanced or metastatic solid tumor not amenable to surgery or curative intent treatment

Must not have

Is currently receiving strong inhibitors of Cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of the study

Has a known history of hepatitis B or known active hepatitis C (HCV) infection

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 5.5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing belzutifan, a medication given alone, in patients with advanced cancers that have specific genetic changes. The drug works by blocking a protein that helps cancer cells grow. Belzutifan showed significant response rates for both Von Hippel-Lindau disease-associated kidney cancers and other types of cancers.

Who is the study for?

This trial is for adults with certain advanced cancers like pheochromocytoma, paraganglioma, pancreatic neuroendocrine tumors, VHL-associated tumors, GIST or solid tumors with HIF-2α alterations. Participants must have a specific diagnosis for each cohort, controlled blood pressure, good organ function and not be pregnant or breastfeeding. They should not have other treatments recently and no major health issues that could affect the study.

What is being tested?

The trial tests belzutifan's effectiveness and safety on its own in treating various advanced cancers related to HIF-2α genetic changes. The main goal is to see how well the cancer responds to belzutifan according to standard response criteria reviewed by independent experts.

What are the potential side effects?

Possible side effects of belzutifan may include fatigue, nausea, anemia (low red blood cell count), hypoxia (low oxygen levels), high blood pressure and liver problems among others. Each person might experience these differently.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with pheochromocytoma or paraganglioma.

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My advanced cancer cannot be removed by surgery or cured with treatment.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I can provide a sample of my tumor for testing.

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My pancreatic neuroendocrine tumor cannot be treated with surgery, radiation, or other local therapies aimed at cure.

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My PPGL cannot be removed by surgery or cured with treatment.

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My blood pressure is under control and I have PPGL.

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My pancreatic cancer has worsened after at least one treatment.

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I have a confirmed diagnosis of GIST based on tissue analysis.

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My pancreatic tumor is confirmed to be a low or intermediate grade neuroendocrine tumor.

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I have been diagnosed with VHL disease.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am taking strong CYP3A4 inhibitors that I cannot stop during the study.

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I have a history of hepatitis B or currently have hepatitis C.

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I have not used any experimental drugs or devices in the last 4 weeks.

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I have been treated with a HIF-2α inhibitor before.

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I am currently being treated for an infection.

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I have a serious heart condition.

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My cancer has spread to my brain or its coverings.

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I have complications like bleeding or blockages that need emergency surgery.

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I need extra oxygen or my oxygen levels are often below 92%.

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I do not have VHL disease.

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I have received an organ or tissue transplant from another person.

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I cannot take pills by mouth or have a condition that affects drug absorption.

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I have had PRRT treatment for my pancreatic neuroendocrine tumor within the last 12 weeks.

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I have had MIBG therapy or similar treatment in the last 3 months.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 5.5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 5.5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 5.5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR)

Secondary study objectives

Disease Control Rate (DCR) as Assessed by BICR

Duration of Response (DOR) as Assessed by BICR

Number of Participants Discontinuing Study Drug due to an AE

+5 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: BelzutifanExperimental Treatment1 Intervention

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Belzutifan

2018

Completed Phase 1

~50

0 / 25Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Pancreatic Neuroendocrine Tumors (pNETs) include somatostatin analogs, mTOR inhibitors, and HIF-2α inhibitors. Somatostatin analogs, such as octreotide and lanreotide, work by inhibiting hormone secretion and tumor growth, providing symptom relief and slowing disease progression. mTOR inhibitors like everolimus target the mTOR pathway, which is involved in cell growth and proliferation, thereby reducing tumor growth. HIF-2α inhibitors, such as belzutifan, target hypoxia-inducible factors that are often overexpressed in tumors, disrupting the tumor's ability to adapt to low oxygen conditions and inhibiting its growth. These treatments are crucial for pNET patients as they offer targeted approaches to manage tumor growth and associated symptoms, improving quality of life and potentially extending survival.

Update of the diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours) [Aktualizacja zaleceń ogólnych dotyczących postępowania diagnostyczno-terapeutycznego w nowotworach neuroendokrynnych układu pokarmowego (rekomendowane przez Polską Sieć Guzów Neuroendokrynnych)].