Clinical trial NCT03108066: MK-3795 (PT2385) for the Treatment of Von Hippel-Lindau Disease-Associated Clear Cell Renal Cell Carcinoma (MK-3795-003)
Official title: An Open Label Phase 2 Study to Evaluate PT2385 for the Treatment of Von Hippel-Lindau Disease-Associated Clear Cell Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: VHL Gene Mutation
VHL
VHL Syndrome
VHL Gene Inactivation
Von Hippel
Von Hippel-Lindau Disease
Von Hippel's Disease
Von Hippel-Lindau Syndrome, Modifiers of
Clear Cell Renal Cell Carcinoma
Clear Cell RCC
ccRCC
Lead sponsor: Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
Collaborators: name: National Institutes of Health (NIH)
First posted: 2017-04-11
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is an open-label Phase 2 study that will be conducted with a 2-stage design.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall Response Rate (ORR) in VHL Disease-Associated ccRCC Tumors
timeFrame: Up to approximately 76 months
Secondary outcomes:
measure: Progression-free Survival (PFS) in VHL Disease-Associated ccRCC Tumors
timeFrame: Up to approximately 76 months
measure: Duration of Response (DOR) in VHL Disease-Associated ccRCC Tumors
timeFrame: Up to approximately 76 months
measure: Time to Response (TTR) in VHL Disease-Associated ccRCC Tumors
timeFrame: Up to approximately 76 months
measure: Overall Response Rate (ORR) in VHL Disease-Associated Non-ccRCC Tumors
timeFrame: Up to approximately 76 months
measure: Progression-free Survival (PFS) in VHL Disease-Associated Non-ccRCC Tumors
timeFrame: Up to approximately 76 months
measure: Duration of Response (DOR) in VHL Disease-Associated Non-ccRCC Tumors
timeFrame: Up to approximately 76 months
measure: Time to Response (TTR) in VHL Disease-Associated Non-ccRCC Tumors
timeFrame: Up to approximately 76 months
measure: MK-3795 Plasma Concentration
timeFrame: Week 1: pre-dose and 6 hours post-dose, Week 3, 5, 9, 13, and 17: pre-dose
measure: MK-3795 Metabolite Plasma Concentration
timeFrame: Week 1: pre-dose and 6 hours post-dose, Week 3, 5, 9, 13, and 17: pre-dose
measure: Number of Participants Who Experienced One or More Adverse Events (AEs)
timeFrame: Up to approximately 76 months
measure: Number of Participants Who Discontinued Study Intervention Due to an AE
timeFrame: Up to approximately 74 months
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Larcher A, Rowe I, Belladelli F, Fallara G, Raggi D, Necchi A, Montorsi F, Capitanio U, Salonia A; OSR VHL Program. Von Hippel-Lindau disease-associated renal cell carcinoma: a call to action. Curr Opin Urol. 2022 Jan 1;32(1):31-39. doi: 10.1097/MOU.0000000000000950.