Study of PAC-1 and Entrectinib for Patients With Metastatic Uveal Melanoma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04589832|
Recruitment Status : Recruiting
First Posted : October 19, 2020
Last Update Posted : February 11, 2021
|Condition or disease||Intervention/treatment||Phase|
|Uveal Melanoma||Drug: PAC-1 Drug: Entrectinib||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||38 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 1B/2 Study of PAC-1 and Entrectinib for Patients With Metastatic Uveal Melanoma|
|Actual Study Start Date :||January 11, 2021|
|Estimated Primary Completion Date :||June 2021|
|Estimated Study Completion Date :||June 2022|
Experimental: Study Treatment Arm
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.
Pharmacokinetic (PK) and pharmacodynamic (PD) assay for PAC-1 will be performed during Days 1 and 21 of Cycle 1. PAC-1 will be given on Day 1 of Cycle 1, withheld on Day 2 and Day 3 of Cycle 1 then reinitiated on Day 4 of Cycle 1 to continue for 21 days of the 28-day cycle. For each successive cycle, PAC-1 therapy will be initiated on Day 1 and continue for 21 days of the 28-day cycle.
Pharmacokinetic and pharmacodynamic assay for entrectinib will be performed during Days 3 and 21 of Cycle 1. Entrectinib therapy will be withheld on Day 1 and Day 2 of Cycle 1, initiated on Day 3 of Cycle 1 and continue for the remainder of the 28 day cycle. For each successive cycle, entrectinib will be intiated on Day 1 and continue for 28 days of the 28-day cycle.
- Phase 1b: Determine maximum tolerated dose (MTD) of PAC-1 [ Time Frame: 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)
- Phase 2: Progression Free Survival at 3 months [ Time Frame: 3 months ]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.
- Incidence and severity of adverse events [ Time Frame: 12 months ]Evaluate the safety of entrectinib and PAC-1 combination, assessed by the incidence and severity of drug-related adverse events (AE), in subjects with metastatic uveal melanoma. CTCAE v5 for grading adverse events
- Overall Response Rate (ORR) [ Time Frame: 12 months ]Number of subjects with complete response and partial response determined as per RECIST 1.1
- Duration of Response (DoR) [ Time Frame: 12 months ]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) [ Time Frame: 12 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
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): NCT04589832
|Contact: Arkadiusz Z Dudek, MD, PhD||657-482-8200||Arkadiusz.Z.Dudek@HealthPartners.com|
|Contact: Ahran Lee||317-634-5842 ext 14||Alee@hoosiercancer.org|
|United States, Minnesota|
|HealthPartners Institute Regions Cancer Care Center||Recruiting|
|Minneapolis, Minnesota, United States, 55440|
|Contact: Arkadiusz Z Dudek, MD 651-254-3321 Arkadiusz.Z.Dudek@HealthPartners.Com|
|Principal Investigator:||Arkadiusz Dudek, MD, PhD||Health Partners Institute|