Four-Part: Effect of GSK2118436 in pts with BRAF Solid Mutant Tumours

• Research type

  Research Study

• Full title

  A Four-Part, Open-Label Study to Evaluate the Effects of Repeat Dose GSK2118436 on the Single Dose Pharmacokinetics of Warfarin, the Effects of Repeat Dose Oral Ketoconazole and Oral Gemfibrozil on the Repeat Dose Pharmacokinetics of GSK2118436, and the Repeat Dose Pharmacokinetics of GSK2118436 in Subjects with BRAF Mutant Solid Tumors.

• IRAS ID

  93689

• Contact name

  Hendrik-Tobias Arkenau

• Sponsor organisation

  ICON Clinical Research

• Eudract number

  2011-004436-61

• ISRCTN Number

  not issued

• 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. Preliminary results from other clinical studies have shown that the repeat dosing of GSK2118436 may also have an effect on a group of enzymes that control drug metabolism. As a result, co-administration of GSK2118436 with other medications (metabolised by this group of enzymes) may reduce the effectiveness of these medications, or reduce the effectiveness of GSK2118436. The purpose of this study is to: (A) investigate the metabolism of GSK2118436 upon repeat dosing, and (B) assess the drug-drug interactions between GSK2118436 and 3 selected medications: warfarin, ketoconazole and gemfibrozil. We will look at the effect that GSK2118436 has - as a perpetrator on warfarin, and as a victim of ketoconazole and gemfibrozil - in order to predict the consequence of GSK2118436 co-administration. 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 assessment 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 roll-over study.

• REC name

  London - West London & GTAC Research Ethics Committee

• REC reference

  12/LO/0190

• Date of REC Opinion

  30 Mar 2012

• REC opinion

  Further Information Favourable Opinion