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

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Brief Title

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

Official Title

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 Phase

Phase 2

Study Type

Interventional


Primary Outcome

Overall Response Rate

Secondary Outcome

 Overall Survival

Condition

Uveal Melanoma

Intervention

BVD-523

Study Arms / Comparison Groups

 BVD-523
Description:  BVD-523 is to be taken twice daily orally for 28 consecutive days

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

13

Start Date

March 26, 2018

Completion Date

August 31, 2025

Primary Completion Date

May 5, 2020

Eligibility Criteria

        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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Elizabeth Buchbinder, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03417739

Organization ID

17-526


Responsible Party

Principal Investigator

Study Sponsor

Dana-Farber Cancer Institute

Collaborators

 BioMed Valley Discoveries, Inc

Study Sponsor

Elizabeth Buchbinder, MD, Principal Investigator, Dana-Farber Cancer Institute


Verification Date

August 2021