A Rollover Study to Provide Continued Treatment With GSK2118436 to Subjects With BRAF Mutation-Positive Tumors - Full Text View

Purpose

This rollover study is designed to provide continued access to GSK2118436 for eligible subjects with BRAF mutation-positive tumors who have previously participated in a GlaxoSmithKline (GSK)-sponsored GSK2118436 study (parent study), who have no evidence of progressive disease and who have tolerated GSK2118436 in the parent study without significant toxicities. Subjects will be enrolled into the appropriate cohort based upon the treatment received in their parent study. Safety assessments (physical examinations, vital signs, 12-lead electrocardiograms, echocardiograms, clinical laboratory assessments, and monitoring of adverse events) will be made throughout the study. Clinical activity will be assessed using local standard of care imaging practices and the appropriate response criteria as determined by the investigator.

Condition	Intervention	Phase
Cancer	Drug: GSK2118436 Drug: GSK1120212 Drug: Other approved anti-cancer agent	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Rollover Study to Provide Continued Treatment With GSK2118436 to Subjects With BRAF Mutation-Positive Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Number of participants with adverse events, as a measure of safety and tolerability [ Time Frame: From date of transition into this Rollover study until 28 days following the last dose. Subjects may continue to receive study medication until disease progression, death or unacceptable adverse event; there is no time limit for this outcome measure. ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	200
Study Start Date:	November 2010
Estimated Study Completion Date:	August 2016
Estimated Primary Completion Date:	August 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Cohort A Subjects who have received </= 8 weeks of GSK2118436 monotherapy in the parent study	Drug: GSK2118436
Experimental: Cohort B Subjects who have received >8 weeks of continuous treatment with GSK2118436 either as monotherapy or combination therapy with another approved anti-cancer agent	Drug: GSK2118436 Drug: Other approved anti-cancer agent
Experimental: Cohort C Subjects who have received >8 weeks of continuous treatment with GSK2118436 in combination with a MEK inhibitor, GSK1120212	Drug: GSK2118436 Drug: GSK1120212

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Has provided signed written informed consent for this study
Has demonstrated compliance with study drug(s), treatment visit schedules, and the requirements and restrictions listed in the consent form
Is currently participating in a GSK-sponsored study of GSK2118436
Currently has no evidence of progressive disease, as determined by the investigator, following previous treatment with GSK2118436 (either as monotherapy or as part of a combination treatment regimen)
For Cohort C only: Subjects must have a calcium phosphate product (CPP) of <4.4 mmol^2/L^2 (55 mg^2/dL^2) if they are to continue treatment with GSK1120212
Continued ability to swallow and retain orally administered study drug(s) and does not have any clinically significant GI abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
Women of childbearing potential and men with reproductive potential must be willing to continue practicing acceptable methods of birth control during the study NOTE: Oral contraceptives are not reliable due to potential drug-drug interaction with GSK2118436
Women of childbearing potential must have a negative serum pregnancy test at the time of transition to this study and before the first dose of study treatment
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category

Exclusion Criteria:

Permanent discontinuation of GSK2118436 in the parent study due to toxicity or disease progression
Local access to commercially available GSK2118436
Currently receiving treatment with any prohibited medication(s)
Any unresolved toxicity > Grade 2 (National Cancer Institute-Common Toxicity Criteria for Adverse Events [NCI-CTCAE], version 4.0) from parent study treatment, except for alopecia, will need to be approved by the GSK Medical Monitor
Uncontrolled diabetes, hypertension or other medical conditions at the time of transition to this study that may interfere with assessment of toxicity
Presence of rheumatoid arthritis
Corrected QT (QTc) interval >/= 480 msec at the time of transition to this study
Left ventricular ejection fraction (LVEF) </= institutional lower limit of normal (LLN) by ECHO at the time of transition to this study
Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system at the time of transition to this study
Pregnant or lactating female
Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions at the time of transition to this study that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the investigator or GSK Medical Monitor

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01231594

Contacts

Contact: US GSK Clinical Call Center

877-379-3718

GSKClinicalSupportHD@gsk.com

Show 27 Study Locations

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT01231594 History of Changes
Other Study ID Numbers:	114144
Study First Received:	October 21, 2010
Last Updated:	May 16, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:

BRAF Inhibitor
Cancer
Safety
GSK2118436
BRAF mutation positive tumors

Additional relevant MeSH terms:

Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013