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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01231594
• Collaborator: (none)
• Enrollment: 214
• Locations: 44
• Arms: 3
• Actual Duration (Months): 89.1
• Patients Per Site: 4.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cancer	Drug: GSK2118436; Drug: GSK1120212; Drug: Other approved anti-cancer agent	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 214 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Rollover Study to Provide Continued Treatment With GSK2118436 to Subjects With BRAF Mutation-Positive Tumors
• Actual Study Start Date: Nov 5, 2010
• Actual Primary Completion Date: Apr 9, 2018
• Actual Study Completion Date: Apr 9, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A Subjects who have received </= 8 weeks of GSK2118436 monotherapy in the parent study	Drug: GSK2118436; Study Drug
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; Study Drug; Drug: Other approved anti-cancer agent; Study Drug
Experimental: Cohort C Subjects who have received >8 weeks of continuous treatment with GSK2118436 in combination with a MEK inhibitor, GSK1120212	Drug: GSK2118436; Study Drug; Drug: GSK1120212; Study Drug

Outcome Measures

Primary Outcome Measures

1. Number of participants with adverse events, as a measure of safety and tolerability [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 Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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/L2 (55 mg^2/dL2) 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

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Goodyear	Arizona	United States	85338
2	Novartis Investigative Site	Scottsdale	Arizona	United States	85259
3	Novartis Investigative Site	Tucson	Arizona	United States	85724-5024
4	Novartis Investigative Site	Los Angeles	California	United States	90025
5	Novartis Investigative Site	Los Angeles	California	United States	90095-7059
6	Novartis Investigative Site	San Francisco	California	United States	94115
7	Novartis Investigative Site	Sarasota	Florida	United States	34232
8	Novartis Investigative Site	Ann Arbor	Michigan	United States	48109
9	Novartis Investigative Site	Detroit	Michigan	United States	48201
10	Novartis Investigative Site	Lebanon	New Hampshire	United States	03756
11	Novartis Investigative Site	New York	New York	United States	10016
12	Novartis Investigative Site	New York	New York	United States	10065
13	Novartis Investigative Site	Columbus	Ohio	United States	43210
14	Novartis Investigative Site	Oklahoma City	Oklahoma	United States	73104
15	Novartis Investigative Site	Philadelphia	Pennsylvania	United States	19111
16	Novartis Investigative Site	Pittsburgh	Pennsylvania	United States	15232
17	Novartis Investigative Site	Greenville	South Carolina	United States	29605
18	Novartis Investigative Site	Memphis	Tennessee	United States	38120
19	Novartis Investigative Site	Nashville	Tennessee	United States	37203
20	Novartis Investigative Site	Nashville	Tennessee	United States	37232-5536
21	Novartis Investigative Site	Dallas	Texas	United States	75246
22	Novartis Investigative Site	Houston	Texas	United States	77030
23	Novartis Investigative Site	San Antonio	Texas	United States	78229
24	Novartis Investigative Site	Salt Lake City	Utah	United States	84112
25	Novartis Investigative Site	Tacoma	Washington	United States	98405
26	Novartis Investigative Site	Randwick	New South Wales	Australia	2031
27	Novartis Investigative Site	Westmead	New South Wales	Australia	2145
28	Novartis Investigative Site	Adelaide	South Australia	Australia	5000
29	Novartis Investigative Site	Heidelberg	Victoria	Australia	3084
30	Novartis Investigative Site	Melbourne	Victoria	Australia	3004
31	Novartis Investigative Site	Nedlands	Western Australia	Australia	6009
32	Novartis Investigative Site	Toronto	Ontario	Canada	M5G 2M9
33	Novartis Investigative Site	Lille		France	59037
34	Novartis Investigative Site	Essen	Nordrhein-Westfalen	Germany	45122
35	Novartis Investigative Site	Luebeck	Schleswig-Holstein	Germany	23538
36	Novartis Investigative Site	Berlin		Germany	10117
37	Novartis Investigative Site	Napoli	Campania	Italy	80131
38	Novartis Investigative Site	Konin		Poland	62-500
39	Novartis Investigative Site	Warszawa		Poland	02-781
40	Novartis Investigative Site	Barcelona		Spain	08035
41	Novartis Investigative Site	Madrid		Spain	28040
42	Novartis Investigative Site	Sevilla		Spain	41013
43	Novartis Investigative Site	Headington		United Kingdom	OX3 7LJ
44	Novartis Investigative Site	London		United Kingdom	W1G 6AD

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01231594
• Other Study ID Numbers: 114144
• First Posted: Nov 1, 2010
• Last Update Posted: Mar 22, 2019
• Last Verified: Mar 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: BRAF Inhibitor; Cancer; Safety; GSK2118436; BRAF mutation positive tumors
• Additional relevant MeSH terms: Trametinib; Dabrafenib; Antineoplastic Agents

Study Results

No Results Posted as of Mar 22, 2019