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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
Last Update Posted : June 16, 2020
Sponsor:
Collaborator:
BioMed Valley Discoveries, Inc
Information provided by (Responsible Party):
Elizabeth Buchbinder, Dana-Farber Cancer Institute

Tracking Information
First Submitted Date  ICMJE January 25, 2018
First Posted Date  ICMJE January 31, 2018
Last Update Posted Date June 16, 2020
Actual Study Start Date  ICMJE March 26, 2018
Actual Primary Completion Date May 11, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 25, 2018)
Overall Response Rate [ Time Frame: 3 months - 2 years ]
Tumor measurement by CT or other imaging method at initial imaging and subsequent imaging with responses graded by RECIST criteria.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 30, 2018)
  • Overall Survival [ Time Frame: 2 years ]
    The time from study enrollment until death.
  • Disease Control Rate [ Time Frame: 3 months - 2 years ]
    A combination of patients who experience complete response, partial response and stable disease on CT or other form of imaging
  • Time to Tumor Progression [ Time Frame: 2 years ]
    Time from enrollment on study until the tumor is progressing by RECIST criteria
  • Duration of Response Rate [ Time Frame: 2 years ]
    Time when initial complete response or partial response is initially recorded until the first date that recurrent or progressive disease is documented.
  • Incidence of treatment associated adverse events [ Time Frame: 2 years ]
    Monitoring for adverse events and severe adverse events associated with study therapy.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 25, 2018)
  • Overall Survival [ Time Frame: 2 years ]
    The time from study enrollment until death.
  • Disease Control Rate [ Time Frame: 3 months - 2 years ]
    A combination of patients who experience complete response, partial response and stable disease on CT or other form of imaging
  • Time to Tumor Progression [ Time Frame: 2 years ]
    Time from enrollment on study until the tumor is progressing by RECIST criteria
  • Duration of Response Rate [ Time Frame: 2 years ]
    Time when initial complete response or partial response is initially recorded until the first date that recurrent or progressive disease is documented.
  • Safety and Tolerability [ Time Frame: 2 years ]
    Monitoring for adverse events and severe adverse events associated with study therapy.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase II Study of BVD-523 in Metastatic Uveal Melanoma
Official Title  ICMJE A Phase II Study of BVD-523 in Metastatic Uveal Melanoma
Brief Summary This research study is studying a targeted therapy called BVD-523 as a possible treatment for advanced uveal melanoma.
Detailed Description

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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Uveal Melanoma
Intervention  ICMJE Drug: BVD-523
In the laboratory BVD-523 works against proteins called ERK to decrease tumor growth
Study Arms  ICMJE Experimental: BVD-523
BVD-523 is to be taken twice daily orally for 28 consecutive days
Intervention: Drug: BVD-523
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 26, 2019)
13
Original Estimated Enrollment  ICMJE
 (submitted: January 25, 2018)
25
Estimated Study Completion Date  ICMJE August 31, 2025
Actual Primary Completion Date May 11, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participants must have histologically or cytologically confirmed stage IV uveal melanoma
  • Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam. See Section 11 for the evaluation of measurable disease.
  • Patients can have received any number of prior therapies for treatment of their uveal melanoma excluding prior treatment with an ERK inhibitor. Patients who have received prior MEK inhibition or other MAPK targeted agents will be allowed on study.
  • Age ≥ 18 years of age.
  • ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
  • Life expectancy of greater than 6 months
  • Participants must have normal organ and marrow function as defined below:

    • leukocytes ≥3,000/mcL
    • hemoglobin ≥9.0 g/dL
    • absolute neutrophil count ≥1,500/mcL
    • platelets ≥100,000/mcL
    • total bilirubin ≤1.5 × institutional upper limit of normal AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal, unless there is known liver involvement in which case ≤5.0 × institutional upper limit of normal
    • creatinine within normal institutional limits OR
    • creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
  • Participants must have adequate cardiac function, e.g. left ventricular ejection fraction (LVEF) of >50% as assessed by multi-gated acquisition (MUGA) or ultrasound/echocardiography (ECHO); corrected QT interval (QTc) <470ms.
  • Presence of metastatic disease that would be amenable to the required biopsies. Ideally pre and post biopsies should be from the same lesion and otherwise from lesions in the same organ. If not possible, then biopsy of the lesions in different organs will be permitted.
  • The effects of BVD-523 on the developing human fetus are unknown. For this reason and because ERK inhibitors could potentially be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 4 months after completion of BVD-523 administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of BVD-523 administration.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C), small molecule targeted therapy (i.e. - kinase inhibitors) within 3 weeks or the last dose of antibody therapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
  • Participants who are receiving any other investigational agents.
  • Major surgery within 4 weeks of the first dose of BVD-523. Tumor embolization procedure or ablation procedure within 2 weeks of first dose of BVD-523.
  • Participants with known brain metastases or evidence of leptomeningeal involvement are eligible only if these lesions are treated and both clinically and radiographically stable for at least four weeks. Patients are eligible if they are being treated with a stable dosage of steroids/anticonvulsants, requiring no dose increase for 4 weeks.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to BVD-523.
  • Participants receiving any medications or substances that are known to be strong inhibitors of CYP1A2, CYP2D6, and CYP3A4 or strong inducers of CYP3A4 are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study because BVD-523 is an ERK with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with BVD-523 breastfeeding should be discontinued if the mother is treated with BVD-523.
  • Gastrointestinal (GI) condition which could impair absorption of study medication or inability to ingest study medication.
  • A history of current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
  • Concomitant malignancies or previous malignancies with less than 2 years of disease-free interval at the time of enrollment (except non-melanoma skin cancer, cervical cancer in situ, prostate cancer with undetectable PSA). Other concurrent malignancies must be discussed with the medical monitor prior to enrollment.
  • Patients with melanoma of cutaneous, mucosal or acral-lentiginous origin or of unknown primary.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03417739
Other Study ID Numbers  ICMJE 17-526
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Elizabeth Buchbinder, Dana-Farber Cancer Institute
Study Sponsor  ICMJE Dana-Farber Cancer Institute
Collaborators  ICMJE BioMed Valley Discoveries, Inc
Investigators  ICMJE
Principal Investigator: Elizabeth Buchbinder, MD Dana-Farber Cancer Institute
PRS Account Dana-Farber Cancer Institute
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP