GSK2118436 on Cardiac Repolarization in Patients with BRAF+ Tumours

• Research type

  Research Study

• Full title

  A Two-Part Study to Evaluate the Effect of Repeat Oral Dosing of GSK2118436 on Cardiac Repolarization in Subjects with V600 BRAF Mutation-Positive Tumors: an open-label, dose-escalating safety lead-in study followed by a single-sequence, placebo-controlled, single-blind study

• IRAS ID

  114509

• Contact name

  Hendrik-Tobias Arkenau

• Sponsor organisation

  GlaxoSmithKline Research & Development Ltd

• Eudract number

  2011-004119-21

• Research summary

  BRAF is a gene which controls both cell signalling events and cell growth. As a result of these functions, mutations acquired in the BRAF gene have been associated with human cancers. The frequency of BRAF mutations vary widely between cancers, but appear most frequently (80%) in patients suffering from melanoma. One such drug being investigated to treat BRAF mutation positive tumours is GSK2118436. GSK2118436 is an orally administered, potent and selective inhibitor of BRAF function. By inhibiting BRAF, GSK2118436 may act to prevent downstream events such as unregulated cell growth. The effectiveness of GSK2118436 treatment on BRAF mutation positive tumours is being studied in Phase 3 studies at present. The objective of this study is to evaluate the effect of repeat supratherapeutic doses of orally administered GSK2118436 on patient??s hearts. This study will focus on the effect that GSK2118436 has on cardiac repolarization (the recharging of the electrical signal in the heart muscle that is required after each heart beat). The electrical activity of the heart will be recorded continuously using a Holter monitor worn by participants. BRAF mutation positive cancer patients willing to participate in this study will undergo a series of examinations, assessments, and blood sampling including: - Physical and dermatological examinations - Tumour biopsies - Tumour assessment scans - ECG and ECHO assessment - Blood sampling for pharmacokinetic analysis and safety assessments. Participation will last for less than 2 months, and at the end of the study patients will have the opportunity to continue receiving GSK2118436 as part of a rollover study.

• REC name

  London - Bloomsbury Research Ethics Committee

• REC reference

  12/LO/1867

• Date of REC Opinion

  29 Jan 2013

• REC opinion

  Further Information Favourable Opinion