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A Phase 2 Study of Belzutifan (PT2977, MK-6482) for the Treatment of Von Hippel Lindau (VHL) Disease-Associated Renal Cell Carcinoma (RCC) (MK-6482-004)

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ClinicalTrials.gov Identifier: NCT03401788
Recruitment Status : Active, not recruiting
First Posted : January 17, 2018
Last Update Posted : August 23, 2021
Sponsor:
Information provided by (Responsible Party):
Peloton Therapeutics, Inc.

Brief Summary:
This study is designed to investigate belzutifan as a treatment for VHL disease associated RCC.

Condition or disease Intervention/treatment Phase
VHL - Von Hippel-Lindau Syndrome VHL Gene Mutation VHL Syndrome VHL Gene Inactivation VHL-Associated Renal Cell Carcinoma VHL-Associated Clear Cell Renal Cell Carcinoma Drug: Belzutifan Phase 2

Detailed Description:
This open-label Phase 2 study will evaluate the efficacy and safety of belzutifan in participants with VHL disease who have at least 1 measurable RCC tumor. Belzutifan will be administered orally and treatment will be continuous. Participants will be evaluated radiologically approximately 12 weeks after initiation of treatment and every 12 weeks thereafter while continuing in the study. Changes in VHL disease-associated non-RCC tumors will also be evaluated.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Phase 2 Open Label
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Phase 2 Study to Evaluate PT2977 for the Treatment of Von Hippel Lindau Disease-Associated Renal Cell Carcinoma
Actual Study Start Date : May 2, 2018
Estimated Primary Completion Date : March 29, 2026
Estimated Study Completion Date : March 29, 2026


Arm Intervention/treatment
Experimental: Open Label Belzutifan
Participants receive 120 mg belzutifan orally once daily. Participants may continue to receive belzutifan in the absence of unacceptable treatment related toxicity or unequivocal disease progression.
Drug: Belzutifan
120 mg once daily (three 40 mg oral tablets once daily).
Other Name: PT2977




Primary Outcome Measures :
  1. Objective Response Rate (ORR) in VHL Disease-Associated RCC Tumors [ Time Frame: Up to approximately 4 years ]
    ORR is defined as the percentage of participants in the analysis population who have a best confirmed response of Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). ORR will be assessed by independent review committee (ICR) for the primary analysis.


Secondary Outcome Measures :
  1. Duration of Response (DOR) in VHL Disease-Associated RCC Tumors [ Time Frame: Up to approximately 4 years ]
    DOR is defined as the interval from the first documented evidence of a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 until Progressive Disease (PD) or death due to any cause, whichever occurs first, in participants demonstrating a best confirmed response of CR or PR. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.

  2. Time to Response (TTR) in VHL Disease-Associated RCC Tumors [ Time Frame: Up to approximately 4 years ]
    TTR is defined as the interval from the start of study treatment to the first documentation of a response per RECIST 1.1, and calculated for participants with a best confirmed response of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions).

  3. Progression-free Survival (PFS) in VHL Disease-Associated RCC Tumors [ Time Frame: Up to approximately 4 years ]
    PFS is defined as the interval from the start of study treatment to the first documented PD or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.

  4. Time to Surgery (TTS) in VHL Disease-Associated RCC Tumors [ Time Frame: Up to approximately 4 years ]
    TTS was defined as the interval from the start of study treatment to the date of surgery.

  5. ORR in VHL Disease-Associated Non-RCC Tumors [ Time Frame: Up to approximately 4 years ]
    ORR is defined as the percentage of participants in the analysis population who have a best confirmed response of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1.

  6. DOR in VHL Disease-Associated Non-RCC Tumors [ Time Frame: Up to approximately 4 years ]
    DOR is defined as the interval from the first documented evidence of a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 until PD or death due to any cause, whichever occurs first, in participants demonstrating a best confirmed response of CR or PR. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.

  7. TTR in VHL Disease-Associated Non-RCC Tumors [ Time Frame: Up to approximately 4 years ]
    TTR is defined as the interval from the start of study treatment to the first documentation of a response per RECIST 1.1, and calculated for participants with a best confirmed response of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions).

  8. PFS in VHL Disease-Associated Non-RCC Tumors [ Time Frame: Up to approximately 4 years ]
    PFS is defined as the interval from the start of study treatment to the first documented PD or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.

  9. TTS in VHL Disease-Associated Non-RCC Tumors [ Time Frame: Up to approximately 4 years ]
    TTS was defined as the interval from the start of study treatment to the date of surgery.

  10. Number of Participants Experiencing an Adverse Event (AE) [ Time Frame: Up to approximately 4 years ]
    An AE is any untoward medical occurrence in a participant regardless of its causal relationship to study treatment. An AE can be any unfavorable and unintended sign (including any clinically significant abnormal laboratory test result), symptom, or disease temporally associated with the use of the study drug, whether or not it is considered to be study drug related.

  11. Number of Participants Experiencing a Serious Adverse Event (SAE) [ Time Frame: Up to approximately 4 years ]
    An SAE is any AE occurring at any dose and regardless of causality that meets any of the following criteria: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, is a congenital anomaly or birth defect in an offspring of a participant taking study drug, or is an important medical event.

  12. Belzutifan Plasma Concentration [ Time Frame: Weeks 1 and 3: pre-dose, 2 and 5 hours post-dose, Week 5, 9, and 13: post-dose. ]
    Blood samples for the determination of belzutifan concentration will be collected at pre-specified timepoints before and after treatment administration.

  13. Belzutifan Metabolite Plasma Concentration [ Time Frame: Weeks 1 and 3: pre-dose, 2 and 5 hours post-dose, Week 5, 9, and 13: post-dose. ]
    Blood samples for the determination of belzutifan metabolite concentration will be collected at pre-specified timepoints before and after treatment administration.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has a diagnosis of von Hippel Lindau disease, based on a germline VHL alteration
  • Has at least 1 measurable solid RCC tumor and no RCC tumor that requires immediate surgical intervention. The diagnosis of RCC can be radiologic (histologic diagnosis not required). Participants may have VHL disease-associated tumors in other organ systems

Exclusion Criteria:

  • Has received prior treatment with belzutifan or another HIF-2α inhibitor
  • Has had any systemic anti-cancer therapy (includes anti-vascular endothelial growth factor [VEGF] therapy or any systemic investigational anti-cancer agent)
  • Has an immediate need for surgical intervention for tumor treatment
  • Has evidence of metastatic disease on screening imaging

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03401788


Locations
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United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Pennsylvania
University of Pennsylvania Medical Center
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
Vanderbilt Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Denmark
Aarhus University Hospital
Aarhus, Denmark
France
Hospital Georges Pompidou
Paris, France
United Kingdom
Cambridge University Hospital
Cambridge, United Kingdom
Sponsors and Collaborators
Peloton Therapeutics, Inc.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
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Responsible Party: Peloton Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03401788    
Other Study ID Numbers: 6482-004
PT2977-202 ( Other Identifier: Peloton Study ID )
2018-000125-30 ( EudraCT Number )
MK-6482-004 ( Other Identifier: Merck )
First Posted: January 17, 2018    Key Record Dates
Last Update Posted: August 23, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Peloton Therapeutics, Inc.:
VHL
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Von Hippel-Lindau Disease
Syndrome
Disease
Pathologic Processes
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Neurocutaneous Syndromes
Nervous System Diseases
Angiomatosis
Vascular Diseases
Cardiovascular Diseases
Ciliopathies
Abnormalities, Multiple
Congenital Abnormalities
Genetic Diseases, Inborn