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

NCT01231594 | Completed Phase 1 FDA Drug

• 1 other identifier: 114144
• Study Type: interventional
• Target: 214
• Locations: 9 countries
• Sites: 44

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.

Conditions

Cancer

Keywords

BRAF Inhibitor; Cancer; Safety; GSK2118436; BRAF mutation positive tumors

Outcome Measures

Primary Outcomes (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.

Study Arms (3)

Cohort A

EXPERIMENTAL

Subjects who have received \</= 8 weeks of GSK2118436 monotherapy in the parent study

Drug: GSK2118436

Cohort B

EXPERIMENTAL

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

Cohort C

EXPERIMENTAL

Subjects who have received \>8 weeks of continuous treatment with GSK2118436 in combination with a MEK inhibitor, GSK1120212

Drug: GSK2118436; Drug: GSK1120212

Interventions

GSK2118436 DRUG

Study Drug

Cohort A; Cohort B; Cohort C

GSK1120212 DRUG

Study Drug

Cohort C

Other approved anti-cancer agent DRUG

Study Drug

Cohort B

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (44)

Novartis Investigative Site

Goodyear, Arizona, 85338, United States

Location

Novartis Investigative Site

Scottsdale, Arizona, 85259, United States

Location

Novartis Investigative Site

Tucson, Arizona, 85724-5024, United States

Location

Novartis Investigative Site

Los Angeles, California, 90025, United States

Location

Novartis Investigative Site

Los Angeles, California, 90095-7059, United States

Location

Novartis Investigative Site

San Francisco, California, 94115, United States

Location

Novartis Investigative Site

Sarasota, Florida, 34232, United States

Location

Novartis Investigative Site

Ann Arbor, Michigan, 48109, United States

Location

Novartis Investigative Site

Detroit, Michigan, 48201, United States

Location

Novartis Investigative Site

Lebanon, New Hampshire, 03756, United States

Location

Novartis Investigative Site

New York, New York, 10016, United States

Location

Novartis Investigative Site

New York, New York, 10065, United States

Location

Novartis Investigative Site

Columbus, Ohio, 43210, United States

Location

Novartis Investigative Site

Oklahoma City, Oklahoma, 73104, United States

Location

Novartis Investigative Site

Philadelphia, Pennsylvania, 19111, United States

Location

Novartis Investigative Site

Pittsburgh, Pennsylvania, 15232, United States

Location

Novartis Investigative Site

Greenville, South Carolina, 29605, United States

Location

Novartis Investigative Site

Memphis, Tennessee, 38120, United States

Location

Novartis Investigative Site

Nashville, Tennessee, 37203, United States

Location

Novartis Investigative Site

Nashville, Tennessee, 37232-5536, United States

Location

Novartis Investigative Site

Dallas, Texas, 75246, United States

Location

Novartis Investigative Site

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

San Antonio, Texas, 78229, United States

Location

Novartis Investigative Site

Salt Lake City, Utah, 84112, United States

Location

Novartis Investigative Site

Tacoma, Washington, 98405, United States

Location

Novartis Investigative Site

Randwick, New South Wales, 2031, Australia

Location

Novartis Investigative Site

Westmead, New South Wales, 2145, Australia

Location

Novartis Investigative Site

Adelaide, South Australia, 5000, Australia

Location

Novartis Investigative Site

Heidelberg, Victoria, 3084, Australia

Location

Novartis Investigative Site

Melbourne, Victoria, 3004, Australia

Location

Novartis Investigative Site

Nedlands, Western Australia, 6009, Australia

Location

Novartis Investigative Site

Toronto, Ontario, M5G 2M9, Canada

Location

Novartis Investigative Site

Lille, 59037, France

Location

Novartis Investigative Site

Essen, North Rhine-Westphalia, 45122, Germany

Location

Novartis Investigative Site

Lübeck, Schleswig-Holstein, 23538, Germany

Location

Novartis Investigative Site

Berlin, 10117, Germany

Location

Novartis Investigative Site

Napoli, Campania, 80131, Italy

Location

Novartis Investigative Site

Konin, 62-500, Poland

Location

Novartis Investigative Site

Warsaw, 02-781, Poland

Location

Novartis Investigative Site

Barcelona, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28040, Spain

Location

Novartis Investigative Site

Seville, 41013, Spain

Location

Novartis Investigative Site

Headington, OX3 7LJ, United Kingdom

Location

Novartis Investigative Site

London, W1G 6AD, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms

Interventions

dabrafenib; trametinib

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2010
• First Posted: November 1, 2010
• Study Start: November 5, 2010
• Primary Completion: April 9, 2018
• Study Completion: April 9, 2018
• Last Updated: March 22, 2019

Record last verified: 2019-03

Locations

IT (1); CA (1); AU (6); FR (1); DE (3); GB (2); PL (2); US (25); ES (3)