Status:
TERMINATED
E6201 and Dabrafenib for the Treatment of Central Nervous System Metastases From BRAF V600 Mutated Metastatic Melanoma
Lead Sponsor:
Mayo Clinic
Conditions:
Clinical Stage IV Cutaneous Melanoma AJCC v8
Metastatic Malignant Neoplasm in the Brain
Eligibility:
All Genders
18+ years
Phase:
PHASE1
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 (c...
Detailed Description
PRIMARY OBJECTIVE: I. To determine the maximum tolerated dose of MEK-1/MEKK-1 inhibitor E6201 (E6201) in combination with dabrafenib in patients with central nervous system (CNS) metastases from BRAF...
Eligibility Criteria
Inclusion
- 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
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
- Hemoglobin (Hb) \>= 9 g/dL without ongoing transfusional support (obtained =\< 15 days prior to registration)
- Absolute neutrophil count (ANC) \>= 1.0 x 10\^9 cells/L without ongoing transfusional support (obtained =\< 15 days prior to registration)
- Platelets \>= 75 x 10\^9 cells/L without ongoing transfusional support (obtained =\< 15 days prior to registration)
- Creatinine =\< 1.5 x the upper limit of normal (ULN), or calculated creatinine clearance \>= 50 mL/minute per the Cockcroft-Gault formula (obtained =\< 15 days prior to registration)
- Total bilirubin =\< 2 times the upper limit of normal (ULN) unless due to Gilbert's disease (obtained =\< 15 days prior to registration)
- Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =\< 2.5 times ULN, or \< 5 times ULN for subjects with liver metastases (obtained =\< 15 days prior to registration)
- Negative serum pregnancy test done =\< 14 days prior to registration, for persons of childbearing potential only, defined as a female who has not undergone a hysterectomy or who has not been naturally post-menopausal for at least 24 consecutive months (i.e., who has had menses any time in the preceding 24 consecutive months)
- Willing to use contraception
- Sexually active persons of childbearing potential (PCBP) and persons able to father a child must agree to use adequate methods to avoid pregnancy throughout the study and for 28 days after the completion of study treatment
- Provide written informed consent
- Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
- Ability to complete Patient Medication Diaries by themselves or with assistance
- Willingness to have institution procure previous BRAF-gene analysis report(s) from a CLIA qualified laboratory, or if a report is not available, willingness to have institution procure archived tumor sample to establish BRAF-mutational melanoma tumor status prior to study
- Ability to swallow
Exclusion
- 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
Key Trial Info
Start Date :
October 20 2022
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
June 2 2025
Estimated Enrollment :
13 Patients enrolled
Trial Details
Trial ID
NCT05388877
Start Date
October 20 2022
End Date
June 2 2025
Last Update
August 19 2025
Active Locations (3)
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1
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
2
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224-9980
3
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905