Clinical Trials

Study closed to enrollment

Inclusion Criteria:

PRE-REGISTRATION ELIGIBILITY CRITERIA

• Willing to provide tissue as required per protocol for central BRAF-V600 mutation testing
  • NOTE: Patients with prior BRAF testing that demonstrate a mutation at V600 will be allowed to enroll prior to central testing if the assay was performed at a Clinical Laboratory Improvement Amendments (CLIA)-certified lab using the COBAS, Pyromark BRAF, Karmonos Detroit Medical Center-University Laboratories (DMC)-UL BRAF, THxID BRAF or Response Genetics BRAF assays; if the assay was based on other methodology other than COBAS, Pyromark BRAF, Karmonos DMC-UL BRAF, THxID BRAF or Response Genetics BRAF assays, the results should be confirmed by central lab testing prior to patient enrollment; should central testing prove to be discordant with initial result (wild-type, non-mutated BRAF), patient will be allowed to continue on study at the discretion of the investigator
• Patients with unknown BRAF status: histologically confirmed melanoma, papillary thyroid, cholangiocarcinoma or testicular cancer that is metastatic or unresectable and for which the investigator feels a BRAF targeted agent is a reasonable treatment
  • NOTE: patient must be screened by central BRAF testing and must demonstrate a V600 mutation prior to start of study agent
  • NOTE: other tumor types without known BRAF mutations will not be eligible for central testing
• Ability to understand and willingness to sign written informed consent
• Life expectancy of > 3 months

REGISTRATION ELIGIBILITY CRITERIA

• Patients with known BRAF-V600 mutation: patients must have BRAF-V600 mutated, histologically confirmed cancer that is metastatic or unresectable and for which curative or standard therapies do not exist or are no longer effective
  • NOTE: Colorectal cancers with BRAF mutations ARE NOT allowed
  • NOTE: Any mutation at the V600 position that results in a change from V (valine) is allowed; this includes E, D, K, R or other mutations not noted here at the V600 position
• Any number of the following prior therapies is allowed:
  • Chemotherapy ≥ 28 days prior to registration
  • Mitomycin C/nitrosoureas ≥ 42 days prior to registration
  • Immunotherapy ≥ 28 days prior to registration
  • Biologic therapy ≥ 28 days prior to registration
  • Radiation therapy ≥ 28 days prior to registration
  • Radiation to < 25% of bone marrow
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Karnofsky ≥ 70%)
• Able to swallow and retain oral medication
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
• Hemoglobin ≥ 9 g/dL
• Platelets ≥ 75 x 10^9/L
• Hepatic and renal function meeting one of the strata below:
  • Group N: Hepatic: normal function (bilirubin ≤ upper limit of normal [ULN]; aspartate aminotransferase [AST] ≤ ULN); Renal: normal function (creatinine clearance [CrCl] ≥ 60 mL/min)
  • Group R3: Hepatic: normal function (bilirubin ≤ ULN; AST ≤ ULN); Renal: severe dysfunction (CrCl ≥ 15 and < 30 mL/min)
  • Group R4: Hepatic: normal function (bilirubin ≤ ULN; AST ≤ ULN; Renal: renal failure (hemodialysis)
  • Group H1: Hepatic: mild dysfunction (bilirubin ≤ ULN; AST > ULN); Renal: acceptable function (CrCl ≥ 60 mL/min)
  • Group H2: Hepatic: moderate dysfunction (bilirubin > ULN and ≤ 3 x ULN; AST > ULN); Renal: acceptable function (CrCl ≥ 60 mL/min)
  • Group H3: Hepatic: severe dysfunction (bilirubin > 3 x ULN and up to investigators discretion; AST > ULN); Renal: acceptable function (CrCl ≥ 60 mL/min)
• Women of childbearing potential must have a negative serum pregnancy test ≤ 7 days prior to registration
• Women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; 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 1 month after completion of dabrafenib administration
• Ability to understand and the willingness to sign a written informed consent document
• Willingness to provide to provide blood and tissue samples as required per protocol
• Patients with a history of clinical benefit from prior RAF inhibitor therapy, as judged by the investigator, will be allowed

Exclusion Criteria:

• Patients with active biliary obstruction; NOTE: patients for which a shunt has been in place for at least 10 days prior to the first dose of dabrafenib are allowed
• Reduced left ventricular ejection fraction (< 50%) or other evidence of cardiac dysfunction as determined by the investigator
• Use of an investigational anti-cancer drug within 28 days preceding the first dose of dabrafenib
• Patients receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450, family 3, subfamily A (CYP3A) or cytochrome P450 family 2, subfamily C, polypeptide 8 (CYP2C8) are ineligible
  • For patients on intermediate inducers or inhibitors, attempts should be made to switch to an alternative agent or delay enrollment until treatment course with concomitant agent completed; if not possible, patient may be enrolled if it is felt to be in the patients best interest as decided by the investigator
  • Weak inhibitors of CYP3A or CYP2C8 should be used with caution and attempts made to limit their use or find alternative agents, if possible
• Warfarin use is provisionally allowed
• Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI CTCAE v4.0) grade 2 or higher from previous anti-cancer therapy, except alopecia
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible; Note: patients not on antiretroviral therapies are eligible for this study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, diabetes mellitus, hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
• Presence of malignancy other than the study indication under this trial within 5 years of study enrollment
• Brain metastases that are symptomatic or untreated or not stable for ≥ 3 months (must be documented by imaging) or requiring corticosteroids; subjects on a stable dose of corticosteroids > 1 month or who have been off corticosteroids for at least 2 weeks can be enrolled with approval of the Cancer Therapy Evaluation Program (CTEP) medical monitor; subjects must also be off enzyme-inducing anticonvulsants for > 4 weeks
• History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 24 weeks; class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; or history of known cardiac arrhythmias unless it has been stably controlled
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to dabrafenib or other agents used in this study
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with dabrafenib
• Any condition or medical problem in addition to the underlying malignancy and organ dysfunction which the investigator feels would pose unacceptable risk