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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01582997
First received: April 5, 2012
Last updated: August 28, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Cancer
Drug: GSK2118436
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: First 28 days for Dose-limiting toxicity, Adverse Events for 1 year ] [ Designated as safety issue: Yes ]
    Adverse Events will be graded by the investigator according to the NCI-CTCAE (version 4.0)


Secondary Outcome Measures:
  • Pharmacokinetics (PK) parameters of GSK2118436 and its metabolites including blood concentration, Cmax and AUC [ Time Frame: For 1 year ] [ Designated as safety issue: No ]
  • Tumor response as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: For 1 year ] [ Designated as safety issue: No ]
  • Serum levels of cytokines [ Time Frame: For 1 year ] [ Designated as safety issue: No ]
  • Expression levels of pERK and Ki67 in tumor tissues if possible [ Time Frame: For 1 year ] [ Designated as safety issue: No ]
  • Gene mutation in tumor tissues, including BRAF and KRAS [ Time Frame: For 1 year ] [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: May 2012
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: GSK2118436
Dose escalation with GSK2118436 may proceed until the overseas recommended phase III dose.

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

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01582997

Locations
Japan
GSK Investigational Site
Shizuoka, Japan, 411-8777
GSK Investigational Site
Tokyo, Japan, 104-0045
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01582997     History of Changes
Other Study ID Numbers: 116056
Study First Received: April 5, 2012
Last Updated: August 28, 2014
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by GlaxoSmithKline:
BRAF
Advance solid tumors

Additional relevant MeSH terms:
Dabrafenib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014