Dabrafenib in Treating Patients With Solid Tumors and Kidney or Liver Dysfunction

Stopped early · Phase 1

Conditions studied: BRAF Gene Mutation, Hepatic Complication, Renal Failure, Solid Neoplasm

In brief

This phase I trial studies the side effects and best dose of dabrafenib in treating patients with solid tumors and kidney or liver dysfunction. Dabrafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Key facts

Study ID

NCT01907802

Run by

National Cancer Institute (NCI)

People needed

8

Starts

2013-08-23

Expected to finish

2015-12-16

Last updated by the study team

2018-08-14

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• PRE-REGISTRATION ELIGIBILITY CRITERIA
• Willing to provide tissue as required per protocol for central BRAF\^V600X mutation testing
• NOTE: patients with prior BRAF\^600X testing that demonstrate a mutation at V600X will be allowed to enroll prior to central testing if the assay was performed at a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory assay; this includes THxID, BRAF Detection Kit, Cobas 4800 BRAF600 mutation test and other CLIA-certified assays available at participating institutions
• Patients with unknown BRAF\^600X status: histologically confirmed melanoma, papillary thyroid, cholangiocarcinoma or testicular cancer that is metastatic or unresectable and for which the investigator feels a BRAF\^600X 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\^600X 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\^V600X mutation: patients must have BRAF\^V600X 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 and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
• Absolute neutrophil count (ANC) >= 1.2 x 10\^9/L
• Hemoglobin >= 9 g/dL
• Platelets >= 100 x 10\^9/L
• Albumin >= 2.5 g/dL

You may not qualify if…

• 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
• History or evidence of cardiovascular risks including any of the following:
• QT interval corrected for heart rate using the Bazett's formula QTcB >= 480 msec
• History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to randomization
• History or evidence of current class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
• Intra-cardiac defibrillators
• Abnormal cardiac valve morphology (>= grade 2) documented by ECHO; (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study
• History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible
• Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti- hypertensive therapy
• 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

Where it is running

• City of Hope Comprehensive Cancer Center — Duarte, California, United States
• USC / Norris Comprehensive Cancer Center — Los Angeles, California, United States
• University of California Davis Comprehensive Cancer Center — Sacramento, California, United States
• City of Hope South Pasadena — South Pasadena, California, United States
• University of Colorado Hospital — Aurora, Colorado, United States
• Mayo Clinic in Florida — Jacksonville, Florida, United States
• University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States
• Johns Hopkins University/Sidney Kimmel Cancer Center — Baltimore, Maryland, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• Wayne State University/Karmanos Cancer Institute — Detroit, Michigan, United States
• Mayo Clinic — Rochester, Minnesota, United States
• Washington University School of Medicine — St Louis, Missouri, United States
• Rutgers Cancer Institute of New Jersey — New Brunswick, New Jersey, United States
• Case Western Reserve University — Cleveland, Ohio, United States
• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States
• University of Pittsburgh Cancer Institute (UPCI) — Pittsburgh, Pennsylvania, United States
• University of Wisconsin Hospital and Clinics — Madison, Wisconsin, United States
• University Health Network-Princess Margaret Hospital — Toronto, Ontario, Canada

Full record on ClinicalTrials.gov

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