Clinical Trial - NCT03417739

A Phase II Study of BVD-523 in Metastatic Uveal Melanoma

Active, not recruiting

Sponsor: Dana-Farber Cancer Institute

Collaborators: BioMed Valley Discoveries, Inc

Information provided by (Responsible party): Principal Investigator Dana-Farber Cancer Institute Elizabeth Buchbinder Principal Investigator

ClinicalTrials.gov Identifier: NCT03417739

Protocol Info

Short Description: Phase II of BVD-523 in Metastatic Uveal Melanoma
Long Description: A Phase II Study of BVD-523 in Metastatic Uveal Melanoma
MGH Status: Closed
Sponsor: DF/HCC
Disease Program: Melanoma

Next Steps


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Purpose

This research study is studying a targeted therapy called BVD-523 as a possible treatment for advanced uveal melanoma.
Condition Title Intervention Phase
Uveal Melanoma BVD-523 Phase 2
Study Type Interventional
Official Title A Phase II Study of BVD-523 in Metastatic Uveal Melanoma

Primary Outcome Measures

Overall Response Rate [Time Frame: 3 months - 2 years] [Designated as safety issue: ]


Secondary Outcome Measures

Overall Survival [Time Frame: 2 years] [Designated as safety issue: ]

Disease Control Rate [Time Frame: 3 months - 2 years] [Designated as safety issue: ]

Time to Tumor Progression [Time Frame: 2 years] [Designated as safety issue: ]

Duration of Response Rate [Time Frame: 2 years] [Designated as safety issue: ]

Incidence of treatment associated adverse events [Time Frame: 2 years] [Designated as safety issue: ]

Estimated Enrollment: 13
Study Start Date: March 2018
Estimated Study Completion Date: August 2025
Estimated Primary Completion Date: August 2021
Arms Assigned Interventions

Experimental:BVD-523

BVD-523 is to be taken twice daily orally for 28 consecutive days
Drug:BVD-523
In the laboratory BVD-523 works against proteins called ERK to decrease tumor growth

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03417739

Locations

  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02214
    • Dana Farber Cancer Institute Boston, Massachusetts, United States, 02215

Sponsors and Collaborators

Dana-Farber Cancer Institute

BioMed Valley Discoveries, Inc

More Information

No publications provided

Responsible Party: Principal Investigator Dana-Farber Cancer Institute Elizabeth Buchbinder Principal Investigator
ClinicalTrials.gov Identifier: NCT03417739
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Dana-Farber Cancer Institute:

Uveal Melanoma

Additional relevant MeSH terms:

Melanoma

Uveal Neoplasms

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on July 18, 2019