Clinical trial NCT01231594: A Rollover Study to Provide Continued Treatment With GSK2118436 to Subjects With BRAF Mutation-Positive Tumors
Official title: A Rollover Study to Provide Continued Treatment With GSK2118436 to Subjects With BRAF Mutation-Positive Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: BRAF Inhibitor
Cancer
Safety
GSK2118436
BRAF mutation positive tumors
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-11-01
Enrollment: 214
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Number of participants with adverse events, as a measure of safety and tolerability
timeFrame: 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.
Secondary outcomes:
Other outcomes:
Locations:
city: Goodyear
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Scottsdale
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Tucson
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: San Francisco
country: United States
facility: Novartis Investigative Site
state: California
city: Sarasota
country: United States
facility: Novartis Investigative Site
state: Florida
city: Ann Arbor
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Detroit
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Lebanon
country: United States
facility: Novartis Investigative Site
state: New Hampshire
city: New York
country: United States
facility: Novartis Investigative Site
state: New York
city: New York
country: United States
facility: Novartis Investigative Site
state: New York
city: Columbus
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Oklahoma City
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: Philadelphia
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Greenville
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Memphis
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Nashville
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Nashville
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: San Antonio
country: United States
facility: Novartis Investigative Site
state: Texas
city: Salt Lake City
country: United States
facility: Novartis Investigative Site
state: Utah
city: Tacoma
country: United States
facility: Novartis Investigative Site
state: Washington
city: Randwick
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Westmead
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Adelaide
country: Australia
facility: Novartis Investigative Site
state: South Australia
city: Heidelberg
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Nedlands
country: Australia
facility: Novartis Investigative Site
state: Western Australia
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Lille
country: France
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
state: Nordrhein-Westfalen
city: Luebeck
country: Germany
facility: Novartis Investigative Site
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Napoli
country: Italy
facility: Novartis Investigative Site
state: Campania
city: Konin
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
city: Headington
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: