Los requisitos de elegibilidad de los participantes incluyen la edad, el sexo, el tipo y el estadio de la enfermedad, y los problemas de salud o tratamientos previos. Las pautas difieren de un estudio a otro e identifican quiénes pueden o no pueden participar. No hay garantía de que cada persona elegible que desee participar en un ensayo se inscribirá. Comunícate con el equipo del estudio para analizar la elegibilidad del estudio y la posible participación.
Inclusion Criteria:
- 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 measurable brain metastasis 0.5 - 3.0 cm, 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) NOTE: Tumor lesions in a previously irradiated area are not considered
measurable disease; disease that is measurable by physical examination only is not eligible
- Asymptomatic or symptomatic CNS metastasis
- Other metastatic melanoma systemic disease is allowed, including leptomeningeal disease
- 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
- Prior immunotherapy for metastatic disease is allowed, if >= 2 weeks have elapsed between the end of therapy and initiation of study treatment
- Prior treatment with BRAF/MEK inhibitor therapy is allowed, if >= 2 weeks have 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 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 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 Criteria:
- 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
- Prior treatment with any chemotherapeutic or investigational agent for =< 4 weeks prior to registration
- Prior treatment with > 2 lines of immunotherapy for metastatic disease
- Prior treatment with > 1 line of a BRAF and/or MEK inhibitor for metastatic disease
- 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
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 6/28/23. Questions