Study of PAC-1 and Entrectinib for Patients With Metastatic Uveal Melanoma
- Registration Number
- NCT04589832
- Lead Sponsor
- Arkadiusz Z. Dudek, MD
- Brief Summary
Single arm study with dose escalation Phase Ib cohort followed by a Phase II cohort. PAC-1 (PO) will be given daily on Days 1 through 21 of each cycle (28-day cycle). Entrectinib (PO) will be given daily on Days 1 through 28 of each cycle. Response will be evaluated after every 2 cycles. Treatment will continue until disease progression based on RECIST criteria or intolerable toxicity.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 6
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Study Treatment Arm PAC-1 Phase 1b will determine the MTD of PAC-1 in combination with entrectinib. Study treatment will include: PAC-1 will be taken orally on Days 1-21 and Entrectinib will be taken orally on Days 1-28 of each 28-day cycle. Treatment will continue until disease progression (based on RECIST 1.1 criteria), unacceptable toxicity, subject withdrawal of informed consent, or subject death either from progression of disease, the therapy itself, or from other causes. Study Treatment Arm Entrectinib Phase 1b will determine the MTD of PAC-1 in combination with entrectinib. Study treatment will include: PAC-1 will be taken orally on Days 1-21 and Entrectinib will be taken orally on Days 1-28 of each 28-day cycle. Treatment will continue until disease progression (based on RECIST 1.1 criteria), unacceptable toxicity, subject withdrawal of informed consent, or subject death either from progression of disease, the therapy itself, or from other causes.
- Primary Outcome Measures
Name Time Method Phase 2: Progression Free Survival at 3 Months Time of treatment start until the criteria for disease progression. PFS is defined as proportion of alive subjects with metastatic uveal melanoma at 3 months from treatment initiation with PAC-1 in combination with entrectinib without evidence of radiological disease progression by RECIST 1.1.
Phase 1b: Determine Maximum Tolerated Dose (MTD) 28 days The MTD of PAC-1 in combination with entrectinib is the highest tested dose of PAC-1 combined with entrectinib with DLT rate of less than 33% in first cycle of therapy (i.e., ≤1 out of 6 subjects with DLT)
- Secondary Outcome Measures
Name Time Method Phase 2: Overall Response Rate (ORR) Start of treatment until disease progression/recurrence Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD.
ORR is defined as the proportion of all subjects with confirmed PR or CR according to RECIST 1.1.Phase 2: Duration of Response (DoR) Time from complete or partial response (whichever status is recorded first) until the date that recurrent or progressive disease. DoR is defined as the time that measurement criteria are met for complete or partial response (whichever status is recorded first) until the date that recurrent or progressive disease is objectively documented
Overall Survival (OS) up to a maximum of 15 months OS is defined as the time from treatment initiation with PAC-1 in combination with entrectinib until death as a result of any cause
Assess Adverse Events AEs will be recorded from time of signed informed consent until 90 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first, up to a maximum of 10 months. The frequency and severity of all treatment related grade 1 and 2 adverse events are reported by CTCAEv5 term and grade.
Trial Locations
- Locations (1)
HealthPartners Institute Regions Cancer Care Center
🇺🇸Minneapolis, Minnesota, United States