Status:
COMPLETED
A Phase I Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of GSK2118436 in Subjects With Solid Tumors
Lead Sponsor:
GlaxoSmithKline
Conditions:
Cancer
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
BRF112680 is a first-time-in-human study to establish the recommended dose and schedule of the orally administered GSK2118436. The recommended dose and regimen will be selected based on the safety, ph...
Eligibility Criteria
Inclusion
- Written informed consent provided.
- 18 years old or older. Subjects enrolled in the midazolam cohort need to be younger than 65 years old.
- Histologically or cytologically confirmed diagnosis of a solid tumor that is not responsive to standard therapies or for which there is no approved or curative therapy. Subjects must have BRAF mutant positive tumors.
- Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
- Able to swallow and retain oral medication.
- Male subjects must agree to use one of the contraception methods listed in the protocol. The criterion must be followed from the time of the first dose of study medication until 16 weeks after the last dose of study medication.
- A female subject is eligible to participate if she is of non-childbearing potential or postmenopausal as defined in the protocol. A female of child-bearing potential may participate if she agrees to use one of the contraception methods listed in the protocol.
- Adequate organ system function as defined in the protocol.
- Part 2/Cohorts A, B and C: Must have radiologically and/or clinically documented disease with at least one measurable lesion as defined by RECIST criteria.
- Part 2/Cohort C only: Must have BRAF positive melanoma with the V600E mutation.
Exclusion
- Currently receiving cancer therapy (chemotherapy, radiation therapy, immuno-therapy, biologic therapy, hormonal therapy, surgery and/or tumor embolization).
- Use of an investigational anti-cancer drug within 28 days preceding the first dose of GSK2118436.
- Current use of a prohibited medication as defined in the protocol or requires any of these medications during treatment with GSK2118436.
- Current use of therapeutic warfarin.
- Any major surgery, radiotherapy, or immunotherapy within 4 weeks prior to first dose. Limited radiotherapy within 2 weeks prior to first dose.
- Chemotherapy regimens with delayed toxicity within four weeks prior to first dose (6 weeks for prior nitrosourea or mitomycin C). Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity within 2 weeks prior to first dose.
- Unresolved toxicity greater than National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0 Grade 1 from previous anti-cancer therapy except alopecia unless agreed to by a GSK Medical Monitor and the investigator.
- Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs.
- A history of known HIV infection.
- Primary malignancy of the central nervous system.
- Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression. Subjects previously treated for these conditions that are asymptomatic and off corticosteroids for at least two weeks are permitted. Brain metastases must be stable for at least 3 months with verification by imaging (brain MRI completed at screening). Subjects are not permitted to receive enzyme inducing anti-epileptic drugs (EIAEDs). In Part 2 of the study, subjects with asymptomatic, untreated brain metastases that have not been stable for 3 months may be enrolled with approval of the GSK medical monitor. These subjects can be on a stable dose of corticosteroids.
- History of alcohol or drug abuse within 6 months prior to the screen visit.
- Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
- Concurrent condition that in the investigator's opinion would jeopardize compliance with the protocol.
- QTc interval greater than or equal to 480 msecs.
- History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within 24 weeks prior to the first dose.
- Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
- Abnormal cardiac valve morphology (subjects with minimally abnormalities can be entered on study with approval from the GSK medical monitor).
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug, or excipients as described in the protocol (to date there are no known FDA approved drugs chemically related to GSK2118436).
- Pregnant or lactating female.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subjects with known glucose 6 phosphate dehydrogenase (G6PD) deficiency.
- Patients positive for HPV. Entry on study allowed only at the discretion of subject and investigator after informed consent regarding discussion of the risk of papillomavirus infection. If enrolled, these subjects must use condoms for sexual activity, regardless of the use of other contraceptive measures and childbearing status.
- Prior treatment with a BRAF or MEK inhibitor unless approved by the GSK medical monitor.
Key Trial Info
Start Date :
June 4 2009
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
March 20 2012
Estimated Enrollment :
170 Patients enrolled
Trial Details
Trial ID
NCT00880321
Start Date
June 4 2009
End Date
March 20 2012
Last Update
November 13 2017
Active Locations (8)
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1
GSK Investigational Site
Los Angeles, California, United States, 90025
2
GSK Investigational Site
New York, New York, United States, 10016
3
GSK Investigational Site
Nashville, Tennessee, United States, 37203
4
GSK Investigational Site
Houston, Texas, United States, 77030