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

NCT01907802 | Terminated Phase 1

• 14 other identifiers: NCI-2013-01338MC12119343P30CA015083U01CA132123U01CA062490U01CA069912UM1CA186644UM1CA186686UM1CA186690UM1CA186691UM1CA186709UM1CA186716UM1CA186717
• Study Type: interventional
• Target: 8
• Locations: 2 countries
• Sites: 18

Brief Summary

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.

Conditions

BRAF Gene Mutation; Hepatic Complication; Renal Failure; Solid Neoplasm

Outcome Measures

Primary Outcomes (2)

• Incidence of toxicities graded according to NCI CTCAE v4.0

  Overall toxicity incidence as well as toxicity profiles by dose level and patient will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

  Up to 30 days after completion of study treatment

• MTD of dabrafenib, defined as the highest dose level that is estimated to induce a dose-limiting toxicity rate less than 33.3% by the two-way isotonic regression, graded according to NCI CTCAE v4.0

  Overall toxicity incidence as well as toxicity profiles by dose level and patient will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

  Up to 28 days

Secondary Outcomes (7)

• Incidence of adverse events graded according to NCI CTCAE v4.0

  Up to 30 days after completion of study treatment

• Best response, defined as the best objective status recorded from the start of treatment until disease progression/recurrence, measured by modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria

  Up to 30 days after completion of study treatment

• Time until any treatment-related toxicity

  Up to 30 days after completion of study treatment

• Time until treatment related grade 3+ toxicity

  Up to 30 days after completion of study treatment

• Time until hematologic nadirs (white blood cells, ANC, platelets)

  Up to 30 days after completion of study treatment

Other Outcomes (2)

• Pharmacokinetic profile of dabrafenib

  Days 1 and 15 of course 1, and day 1 of all subsequent courses

• Pharmacogenetic profile of dabrafenib

  Day 1 prior to treatment

Study Arms (1)

Treatment (dabrafenib)

EXPERIMENTAL

Patients receive dabrafenib PO BID on days 1-28 (QD on day 1 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Dabrafenib; Other: Laboratory Biomarker Analysis; Other: Pharmacogenomic Study; Other: Pharmacological Study

Interventions

Dabrafenib DRUG

Given PO

Also known as: BRAF Inhibitor GSK2118436, GSK-2118436A, GSK2118436

Treatment (dabrafenib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (dabrafenib)

Pharmacogenomic Study OTHER

Correlative studies

Also known as: PHARMACOGENOMIC

Treatment (dabrafenib)

Pharmacological Study OTHER

Correlative studies

Treatment (dabrafenib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• Glaxosmithkline Biologicals S.A.: collaborator

Study Sites (18)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

dabrafenib; Pharmacogenomic Testing

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Genetic Testing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Ramesh Ramanathan

  Mayo Clinic Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2013
• First Posted: July 25, 2013
• Study Start: August 23, 2013
• Primary Completion: December 16, 2015
• Study Completion: December 16, 2015
• Last Updated: August 14, 2018

Record last verified: 2018-08

Locations

US (17); CA (1)