Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01231594




Registration number
NCT01231594
Ethics application status
Date submitted
21/10/2010
Date registered
1/11/2010
Date last updated
22/03/2019

Titles & IDs
Public title
A Rollover Study to Provide Continued Treatment With GSK2118436 to Subjects With BRAF Mutation-Positive Tumors
Scientific title
A Rollover Study to Provide Continued Treatment With GSK2118436 to Subjects With BRAF Mutation-Positive Tumors
Secondary ID [1] 0 0
114144
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK2118436
Treatment: Drugs - GSK1120212
Treatment: Drugs - Other approved anti-cancer agent

Experimental: Cohort A - Subjects who have received </= 8 weeks of GSK2118436 monotherapy in the parent study

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

Experimental: Cohort C - Subjects who have received >8 weeks of continuous treatment with GSK2118436 in combination with a MEK inhibitor, GSK1120212


Treatment: Drugs: GSK2118436
Study Drug

Treatment: Drugs: GSK1120212
Study Drug

Treatment: Drugs: Other approved anti-cancer agent
Study Drug
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with adverse events, as a measure of safety and tolerability
Timepoint [1] 0 0
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.

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/11/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/04/2018
Sample size
Target
Accrual to date
Final
214
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Randwick
Recruitment hospital [2] 0 0
Novartis Investigative Site - Westmead
Recruitment hospital [3] 0 0
Novartis Investigative Site - Adelaide
Recruitment hospital [4] 0 0
Novartis Investigative Site - Heidelberg
Recruitment hospital [5] 0 0
Novartis Investigative Site - Melbourne
Recruitment hospital [6] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
New Hampshire
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Oklahoma
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
South Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Utah
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
France
State/province [16] 0 0
Lille
Country [17] 0 0
Germany
State/province [17] 0 0
Nordrhein-Westfalen
Country [18] 0 0
Germany
State/province [18] 0 0
Schleswig-Holstein
Country [19] 0 0
Germany
State/province [19] 0 0
Berlin
Country [20] 0 0
Italy
State/province [20] 0 0
Campania
Country [21] 0 0
Poland
State/province [21] 0 0
Konin
Country [22] 0 0
Poland
State/province [22] 0 0
Warszawa
Country [23] 0 0
Spain
State/province [23] 0 0
Barcelona
Country [24] 0 0
Spain
State/province [24] 0 0
Madrid
Country [25] 0 0
Spain
State/province [25] 0 0
Sevilla
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Headington
Country [27] 0 0
United Kingdom
State/province [27] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01231594
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01231594