Clinical trial NCT01582997: A Phase I Study to Investigate the Safety, Tolerability and Pharmacokinetic Profile of of GSK2118436 in Japanese Subjects With BRAF Mutation Positive Solid Tumors
Official title: An Open-label, Dose Escalation, Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetic Profile of GSK2118436 in Japanese Subjects With BRAF V600 Mutation Positive Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: BRAF
Advance solid tumors
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2012-04-23
Enrollment: 12
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with adverse events as a measure of safety and tolerability
timeFrame: First 28 days for Dose-limiting toxicity, Adverse Events for 1 year
Secondary outcomes:
measure: Pharmacokinetics (PK) parameters of GSK2118436 and its metabolites including blood concentration, Cmax and AUC
timeFrame: For 1 year
measure: Tumor response as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
timeFrame: For 1 year
measure: Serum levels of cytokines
timeFrame: For 1 year
measure: Expression levels of pERK and Ki67 in tumor tissues if possible
timeFrame: For 1 year
measure: Gene mutation in tumor tissues, including BRAF and KRAS
timeFrame: For 1 year
Other outcomes:
Locations:
city: Shizuoka
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Fujiwara Y, Yamazaki N, Kiyohara Y, Yoshikawa S, Yamamoto N, Tsutsumida A, Nokihara H, Namikawa K, Mukaiyama A, Zhang F, Tamura T. Safety, tolerability, and pharmacokinetic profile of dabrafenib in Japanese patients with BRAF V600 mutation-positive solid tumors: a phase 1 study. Invest New Drugs. 2018 Apr;36(2):259-268. doi: 10.1007/s10637-017-0502-8. Epub 2017 Sep 7.