A Phase II Study of BVD-523 in 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. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03417739|
Recruitment Status : Active, not recruiting
First Posted : January 31, 2018
Results First Posted : November 11, 2021
Last Update Posted : November 23, 2021
|Condition or disease||Intervention/treatment||Phase|
|Uveal Melanoma||Drug: BVD-523||Phase 2|
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved BVD-523 as a treatment for any disease.
BVD-523 has been tested in patients with solid tumors to determine the highest dose of BVD-523 that can be safely given to patients.
In this research study, the investigators are evaluating the role of BVD-523 in the treatment of patients with uveal melanoma. Genetic changes within metastatic uveal melanoma activate proteins in the MAPK protein signaling pathway which leads to tumor growth. In the laboratory BVD-523 works against one of these proteins called ERK to decrease tumor growth. In this study, the investigators are testing BVD-523 to see if it works to treat metastatic uveal melanoma.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||13 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of BVD-523 in Metastatic Uveal Melanoma|
|Actual Study Start Date :||March 26, 2018|
|Actual Primary Completion Date :||May 5, 2020|
|Estimated Study Completion Date :||August 31, 2025|
BVD-523 is administered at the RP2D of 600mgs taken twice daily orally for 28 consecutive days (1 cycle). Planned does may modified based on toxicity.
ERK1 and ERK2 inhibitor
Other Name: Ulixertinib
- Overall Response Rate [ Time Frame: up to 52 weeks ]Overall Response Rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
- Disease Control Rate [ Time Frame: up to 52 weeks ]A combination of patients who experience complete response, partial response and stable disease on CT or other form of imaging
- Median Overall Survival [ Time Frame: Participant survival information will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure. Median follow-up was 6 months. ]OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.
- Median Time to Tumor Progression [ Time Frame: Between the dates of the start of trial treatment and first documentation of progressive disease. In the absence of documented progressive disease, follow-up will be censored at date of last disease assessment. up to 52 weeks ]Time from enrollment on study until the tumor is progressing by RECIST v1.0 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
- To Evaluate the Pharmacodynamics of ERK Inhibition on BVD-523 With a Comparison of Pre- and On-treatment Biopsies. [ Time Frame: Tumor biopsies are obtained 7-28 days prior to the first treatment and 12-16 days following the initial treatment in order to facilitate ERK signaling analysis, mutation analysis, sequencing, and cell line development. ]MAPK pathway inhibition will be analyzed in pre-treatment and post-treatment samples to understand the effect of ERK inhibition by BVD-523
- To Better Understand the Genetic Variability of Uveal Melanoma Through Whole Exome Sequencing [ Time Frame: Tumor biopsies are obtained 7-28 days prior to the first treatment and 12-16 days following the initial treatment in order to facilitate ERK signaling analysis, mutation analysis, sequencing, and cell line development. ]DNA sequencing will occur in tissue samples from patients treated on study to gain a better understanding of the genetic variability observed in uveal melanoma
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): NCT03417739
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02214|
|Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|Principal Investigator:||Elizabeth Buchbinder, MD||Dana-Farber Cancer Institute|