E6201 and Dabrafenib for the Treatment of Central Nervous System Metastases From BRAF V600 Mutated Metastatic Melanoma

NCT05388877 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: MC210703NCI-2022-0413322-000531
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I tests the safety, side effects, and best dose of E6201 in combination with dabrafenib in treating patients with BRAF V600 mutated melanoma that has spread to the central nervous system (central nervous system metastases). E6201 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Dabrafenib is used in patients whose cancer has a mutated (changed) form of a gene called BRAF. It is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps stop the spread of tumor cells. Giving E6201 and dabrafenib together may work better in treating patients with BRAF V600 mutated melanoma that has spread to the central nervous system than either drug alone.

Conditions

Clinical Stage IV Cutaneous Melanoma AJCC v8; Metastatic Malignant Neoplasm in the Brain; Metastatic Malignant Neoplasm in the Central Nervous System; Metastatic Melanoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

  Up to end of cycle 1 (1 cycle = 28 days)

Secondary Outcomes (5)

• Overall intracranial response rate

  Up to 2 years

• Overall extracranial response rate

  Up to 2 years

• Incidence of adverse events

  Up to 2 years

• Time to first progression

  Up to 2 years

• Overall survival

  Up to 2 years

Other Outcomes (1)

• BRAF mutational status

  Up to 2 years

Study Arms (1)

Treatment (E6201, dabrafenib)

EXPERIMENTAL

Patients receive MEK-1/MEKK-1 inhibitor E6201 IV over 2 hours on days 1, 4, 8, 11, 15, and 18, and dabrafenib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Dabrafenib; Drug: MEK-1/MEKK-1 Inhibitor E6201; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging

Interventions

Dabrafenib DRUG

Given PO

Also known as: BRAF Inhibitor GSK2118436, GSK-2118436, GSK-2118436A, GSK2118436

Treatment (E6201, dabrafenib)

MEK-1/MEKK-1 Inhibitor E6201 DRUG

Given IV

Also known as: E-6201, E6201

Treatment (E6201, dabrafenib)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (E6201, dabrafenib)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Treatment (E6201, dabrafenib)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, nuclear magnetic resonance, sMRI, Structural MRI

Treatment (E6201, dabrafenib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>= 18 years
• Histologically or cytologically confirmed stage IV metastatic BRAF V600-mutated melanoma
• Documented metastasis of the primary tumor to the CNS
• BRAF-mutation melanoma tumor status will be established prior to entry based on previous BRAF-gene analysis reports from a Clinical Laboratory Improvement Act (CLIA) qualified laboratory. If a report is not available, the mutation analysis will be performed at screening on archival tissue
• At least one brain metastasis, as assessed by magnetic resonance imaging (MRI) or computed tomography (CT) with contrast =\< 3 weeks prior to registration and does not require immediate local intervention (surgery or radiosurgery)
• Asymptomatic or symptomatic CNS metastasis
• Systemic, measurable metastatic melanoma disease is allowed; leptomeningeal disease is allowed.
• Prior stereotactic radiosurgery and/or excision of brain metastases is allowed \> 3 weeks before initiation of study treatment
• Prior immunotherapy for adjuvant or metastatic disease is allowed provided there is documented progression of disease following treatment
• Prior melanoma adjuvant BRAF/MEK inhibitor treatment is allowed if \>= 12 months has elapsed between the end of therapy and initiation of study treatment
• Able to swallow and retain oral medication with no clinically significant gastrointestinal abnormalities that may alter absorption, such as malabsorption syndrome or major resection of the stomach or bowels
• Stable dose of corticosteroids for CNS metastasis is allowed if \>= 7 days
• Seizures due to CNS metastases must be controlled with stable anti-epileptic treatment for \>= 14 days
• Bisphosphonates and/or denosumab are allowed
• Life expectancy \>= 3 months

You may not qualify if:

• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
• Urgent need of treatment to prevent acute neurologic deterioration, including urgent neurosurgery or radiotherapy
• Symptoms of uncontrolled intracranial pressure
• Symptomatic or untreated spinal cord compression
• Serious cardiac condition =\< 6 months prior to registration, such as uncontrolled arrhythmia, myocardial infarction, unstable angina, or heart disease defined by the New York Heart Association (NYHA) class III or class IV
• Failure to recover from acute, reversible effects of prior therapy regardless of interval since last treatment
• Uncontrolled intercurrent non-cardiac illness including, but not limited to:
• Ongoing or active infection requiring IV antibiotic usage within the last week prior to study treatment
• Any other conditions that would limit compliance with study requirements or confound the interpretation of study results
• Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy
• NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
• Any of the following, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
• Pregnant persons
• Nursing persons
• Persons of childbearing potential who are unwilling to employ adequate contraception

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Brain Neoplasms; Melanoma

Interventions

dabrafenib; 14-(ethylamino)-8,9,16-trihydroxy-3,4-dimethyl-3,4,9,19-tetrahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione; Specimen Handling; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Hani M. Babiker, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2022
• First Posted: May 24, 2022
• Study Start: October 20, 2022
• Primary Completion: November 19, 2024
• Study Completion: June 2, 2025
• Last Updated: August 19, 2025

Record last verified: 2025-08

Locations

US (3)