E6201 Plus Dabrafenib for the Treatment of Metastatic Melanoma Central Nervous System Metastases (CNS)

• Status: Recruiting
• Trial end date: 2021-06-30
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase 1 study of E6201 plus dabrafenib for the treatment of CNS metastases in BRAF V600-mutated metastatic melanoma. A total of up to N=28-34 subjects with melanoma metastasized to the CNS will be included.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Spirita Oncology, LLC; Strategia Therapeutics
• Collaborator: University of Arizona
• Treatments: Dabrafenib

Criteria

Inclusion Criteria:

• Males and females ≥ 18 years of age

• Histologically or cytologically confirmed BRAFV600-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 or MEK pathway mutation reports from a CLIA qualified laboratory. If a report is not available, the mutation analysis will be performed at Screening on archival tissue

• Other metastatic melanoma systemic disease allowed

• At least one measurable brain metastais, 0.5 - 3.0 cm, as assessed by MRI ≤ 3 weeks prior to initiation of study treatment, provided neurological sequelae have resolved completely and at least one measurable metastasis with documented disease progression is present on MRI

• Prior stereotactic radiosurgery and/or excision of up to 3 brain metastases is allowed > 3 weeks before initiation of study treatment, provided neurological sequelae have resolved completely and at least one measurable metastasis with documented disease progression is present on MRI

• One prior line of immunotherapy for metastatic disease is allowed, if ≥ 2 weeks has elapsed between the end of therapy and initiation of study treatment

• Prior melanoma adjuvant immunotherapy is allowed, if ≥ 6 months has elapsed between the end of therapy and initiation of study treatment

• Prior melanoma adjuvant BRAF/MEK inhibitor therapy 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 (Combination Safety Run-in and Expansion Phases of the study only)

• Asymptomatic or symptomatic CNS metastasis is allowed

• Stable dose of corticosteroids for CNS metastasis for ≥ 7 days allowed

• Patients with seizures due to CNS metastases must be controlled with stable anti-epileptic treatment for ≥ 14 days

• Bisphosphonates and/or denosumab are allowed

• Adequate performance status: Eastern Cooperative Oncology Group (ECOG) ≤ 2

• Life expectancy of ≥ 3 months

• Adequate hematologic parameters without ongoing transfusional support:

• Hemoglobin (Hb) ≥ 9 g/dL

• Absolute neutrophil count (ANC) ≥ 1.0 x 10^9 cells/L

• Platelets ≥ 75 x 10^9 cells/L

• Adequate renal and hepatic function:

• Creatinine ≤ 1.5 x the upper limit of normal (ULN), or calculated creatinine clearance ≥ 50 mL/minute x 1.73 m^2

• Total bilirubin ≤ 2 times the upper limit of normal (ULN) unless due to Gilbert's disease

• ALT/AST ≤ 2.5 times ULN, or < 5 times ULN for subjects with liver metastases

• Negative serum pregnancy test within 14 days prior to the first dose of study therapy for women of child-bearing potential (WCBP). Sexually active WCBP and male subjects must agree to use adequate methods to avoid pregnancy throughout the study and for 28 days after the completion of study treatment.

• Ability to provide written informed consent

Exclusion Criteria:

• 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

• Prior treatment with any chemotherapeutic or investigational agent

• Prior treatment with any BRAF and/or MEK inhibitor for metastatic disease

• Prior treatment with > 1 line of immunotherapy for metastatic disease

• Serious cardiac condition within the last 6 months, such as uncontrolled arrhythmia, myocardial infarction, unstable angina or heart disease defined by the New York Heart Association (NYHA) Class III or Class IV

• QT interval corrected for rate (QTc) > 480 msec for on the ECG obtained at Screening using Fridericia method for QTc calculation

• Active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) requiring systemic antiviral treatment within the last week prior to study treatment

• Other active infection requiring IV antibiotic usage within the last week prior to study treatment

• Any other medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence to study requirements or confound the interpretation of study results

• Pregnant or breast-feeding