A Phase I Study to Investigate the Safety, Tolerability and Pharmacokinetic Profile of of GSK2118436 in Japanese Subjects With BRAF Mutation Positive Solid Tumors

Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01582997
• Other study ID #: 116056
• Status: Completed
• Phase: Phase 1
• First received: April 5, 2012
• Last updated: November 8, 2017
• Start date: May 11, 2012
• Est. completion date: April 16, 2015

Study information

• Verified date: November 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: April 16, 2015
• Est. primary completion date: August 1, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• GSK2118436
Dose escalation with GSK2118436 may proceed until the overseas recommended phase III dose.

Locations

Country	Name	City	State
Japan	GSK Investigational Site	Shizuoka
Japan	GSK Investigational Site	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events as a measure of safety and tolerability	Adverse Events will be graded by the investigator according to the NCI-CTCAE (version 4.0)	First 28 days for Dose-limiting toxicity, Adverse Events for 1 year
Secondary	Pharmacokinetics (PK) parameters of GSK2118436 and its metabolites including blood concentration, Cmax and AUC		For 1 year
Secondary	Tumor response as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1		For 1 year
Secondary	Serum levels of cytokines		For 1 year
Secondary	Expression levels of pERK and Ki67 in tumor tissues if possible		For 1 year
Secondary	Gene mutation in tumor tissues, including BRAF and KRAS		For 1 year

External Links

•   Results for study 116056 can be found on the GSK Clinical Study Register.