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Completed

NCT Number: NCT03108066

MK-3795 (PT2385) for the Treatment of Von Hippel-Lindau Disease-Associated Clear Cell Renal Cell Carcinoma (MK-3795-003)

The primary objective of this study is to assess the overall response rate (ORR) of von Hippel-Lindau (VHL) disease-associated clear cell renal cell carcinoma (ccRCC) tumors in VHL participants treated with MK-3795.

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Key information

Conditions

VHL Gene Mutation Abnormalities, Multiple Adenocarcinoma Angiomatosis Carcinoma Carcinoma, Renal Cell Cardiovascular Diseases Ciliopathies Clear Cell RCC Clear Cell Renal Cell Carcinoma Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genetic Diseases, Inborn Kidney Diseases Kidney Neoplasms Male Urogenital Diseases Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Nervous System Diseases Neurocutaneous Syndromes Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms VHL VHL Gene Inactivation VHL Syndrome Vascular Diseases Von Hippel Von Hippel's Disease Von Hippel-Lindau Disease Von Hippel-Lindau Syndrome, Modifiers of ccRCC

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

About this study

This open-label Phase 2 study will evaluate the efficacy, safety, PK, and PD of MK-3795 in participants with VHL disease who have at least 1 measurable VHL disease-associated ccRCC tumor (as defined by RECIST 1.1). MK-3795 will be administered orally and treatment will be continuous. Changes in VHL disease-associated non-ccRCC tumors will also be evaluated.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Has at least 1 measurable ccRCC tumor and no solid ccRCC tumor greater than 3.0 cm, based on radiologic diagnosis (histologic diagnosis not required); may have VHL disease-associated lesions in other organ systems
  • Has a diagnosis of von Hippel Lindau disease, based on a germline VHL alteration

Exclusion criteria

  • Has had prior radiotherapy or systemic anti cancer therapy for ccRCC (includes anti-vascular endothelial growth factor (VEGF) therapy or any systemic investigational anti cancer agent)
  • Has a prior or concomitant non-VHL disease-associated invasive malignancy with the exception of adequately treated basal or squamous cell carcinoma of the skin, cervical carcinoma in situ or any other malignancy from which the participant has remained disease free for more than 2 years
  • Has any history of metastatic disease
  • Has had radiotherapy to any non-ccRCC site within 4 weeks prior to entering the study or has not recovered from adverse events (AE)
  • Has had any surgical procedure for VHL disease or any major surgical procedure completed within 4 weeks prior to entering the study or has any surgical lesions from recent major surgical procedures that are not well healed

Treatment and study plan

MK-3795

Drug

800 mg twice daily (four 200 mg oral tablets twice daily)

Other names: PT2385, PT-2385

Primary outcomes

  1. Overall Response Rate (ORR) in VHL Disease-Associated ccRCC Tumors

    Time frame: Up to approximately 76 months

    ORR was 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 was assessed by independent review committee (ICR) for the primary analysis.

Secondary outcomes

  1. Progression-free Survival (PFS) in VHL Disease-Associated ccRCC Tumors

    Time frame: Up to approximately 76 months

    PFS was defined as the interval from the start of study treatment to the first documented Progressive Disease (PD) or death from any cause, whichever occurs first. Per RECIST 1.1, PD was 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 was also considered PD.

  2. Duration of Response (DOR) in VHL Disease-Associated ccRCC Tumors

    Time frame: Up to approximately 76 months

    DOR was 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 was 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 was also considered PD.

  3. Time to Response (TTR) in VHL Disease-Associated ccRCC Tumors

    Time frame: Up to approximately 76 months

    TTR was 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).

  4. Overall Response Rate (ORR) in VHL Disease-Associated Non-ccRCC Tumors

    Time frame: Up to approximately 76 months

    ORR was 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).

  5. Progression-free Survival (PFS) in VHL Disease-Associated Non-ccRCC Tumors

    Time frame: Up to approximately 76 months

    PFS was 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 was also considered PD.

  6. Duration of Response (DOR) in VHL Disease-Associated Non-ccRCC Tumors

    Time frame: Up to approximately 76 months

    DOR was 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 was 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 was also considered PD.

  7. Time to Response (TTR) in VHL Disease-Associated Non-ccRCC Tumors

    Time frame: Up to approximately 76 months

    TTR was 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. MK-3795 Plasma Concentration

    Time frame: Week 1: pre-dose and 6 hours post-dose, Week 3, 5, 9, 13, and 17: pre-dose

    Blood samples for the determination of MK-3795 concentration were collected at pre-specified timepoints before and after administration of study intervention.

  9. MK-3795 Metabolite Plasma Concentration

    Time frame: Week 1: pre-dose and 6 hours post-dose, Week 3, 5, 9, 13, and 17: pre-dose

    Blood samples for the determination of MK-3795 metabolite concentration were collected at pre-specified timepoints before and after administration of study intervention.

  10. Number of Participants Who Experienced One or More Adverse Events (AEs)

    Time frame: Up to approximately 76 months

    An AE was defined as 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 was considered to be study drug related.

  11. Number of Participants Who Discontinued Study Intervention Due to an AE

    Time frame: Up to approximately 74 months

    An AE was defined as 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.

Sponsors and collaborators

Lead sponsor

Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Industry

Collaborators

  • National Institutes of Health (NIH)

Registry information

Official study title

An Open Label Phase 2 Study to Evaluate PT2385 for the Treatment of Von Hippel-Lindau Disease-Associated Clear Cell Renal Cell Carcinoma

Important dates

Study start
2017
Primary completion
2023
Study completion
2023
First posted
Apr 11, 2017
Registry last updated
Sep 24, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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