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

NCT ID: NCT01582997

Last Updated: 2017-11-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-11
• Study Completion Date: 2015-04-16

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.

Conditions

Cancer

Keywords

BRAF; Advance solid tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Escalation Part

Dose escalation will be conducted to assess safety, tolerability, single and repeat dose PK profile and preliminary efficacy of GSK2118436 . The dose may be escalated to the overseas recommended phase III dose.

Group Type: EXPERIMENTAL

GSK2118436

Intervention Type: DRUG

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

Interventions

GSK2118436

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

Intervention Type: DRUG

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.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Shizuoka, , Japan

GSK Investigational Site

Tokyo, , Japan

Countries

Japan

References

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.

Reference Type: DERIVED

PMID: 28879519 (View on PubMed)

Other Identifiers

116056

Identifier Type: -

Identifier Source: org_study_id