Cancer
Conditions
Keywords
BRAF, Advance solid tumors
Brief summary
BRF116056 is the first clinical experience with GSK2118436, a BRAF inhibitor, in Japan. This study will be designed to assess safety, tolerability, single and repeat dose PK profile and preliminary efficacy of GSK2118436 in Japanese subjects with BRAF V600 mutation positive solid tumors using continuous daily dosing schedule.
Detailed description
BRF116056 is the first clinical experience with GSK2118436, a BRAF inhibitor, in Japan. This study will be designed to assess safety, tolerability, single and repeat dose PK profile and preliminary efficacy of GSK2118436 in Japanese subjects with BRAF V600 mutation positive solid tumors using continuous daily dosing schedule. Dose escalation of GSK2118436 will be performed according to a standard 3+3 dose-escalation design. GSK2118436 is given twice a day. However, to characterize the PK of GSK2118436 and its metabolites after single-dose administration, GSK2118436 will NOT be administrated for a week after the first administration. GSK2118436 continuous dosing will start after the 168-hour PK sample is obtained. Subjects may receive study treatment until disease progression, death or an unacceptable adverse event.
Interventions
DRUGGSK2118436
Dose escalation with GSK2118436 may proceed until the overseas recommended phase III dose.
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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 V600E or K mutant positive tumors. * Women with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 4 weeks after the last dose of study medication. * Men with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 16 weeks after the last dose of study medication. * Must have adequate organ function. * Must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
Exclusion criteria
* Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy or surgery). * Use of an investigational anti-cancer drug within 28 days preceding the first dose of GSK2118436. * A history of other malignancy. Subjects who have been disease-free for 5 years or subjects with a history of complete resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. * History of Human Immunodeficiency Virus (HIV) infection. * Certain cardiac abnormalities. * Pregnant or lactating female.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events as a measure of safety and tolerability | First 28 days for Dose-limiting toxicity, Adverse Events for 1 year | Adverse Events will be graded by the investigator according to the NCI-CTCAE (version 4.0) |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK) parameters of GSK2118436 and its metabolites including blood concentration, Cmax and AUC | For 1 year |
| Tumor response as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | For 1 year |
| Serum levels of cytokines | For 1 year |
| Expression levels of pERK and Ki67 in tumor tissues if possible | For 1 year |
| Gene mutation in tumor tissues, including BRAF and KRAS | For 1 year |
Countries
Japan
Outcome results
None listed