Study of Trametinib in children and adolescent subjects with Cancer

• Research type

  Research Study

• Full title

  An Open-Label, Dose-Escalation, Phase I/II Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of the MEK Inhibitor Trametinib in Children and Adolescents Subjects with Cancer or Plexiform Neurofibromas and Trametinib in Combination with Dabrafenib in Children and Adolescents with Cancers Harboring V600 mutations.

• IRAS ID

  157131

• Contact name

  Hira Sajjad

• Contact email

  hira.sajjad@parexel.com

• Sponsor organisation

  GlaxoSmithKline Research & Development Ltd

• Eudract number

  2013-003596-35

• Duration of Study in the UK

  2 years, 6 months, 0 days

• Research summary

  Trametinib (an anti-cancer drug) has been tested in humans and animals with different cancer types, but has not been tested in the paediatric population.

  In this study, GSK (study sponsor) is looking to assess the safety of trametinib at different dose levels in children and adolescents. The study will also look at the combination of trametinib with dabrafenib in treating cancer in children and adolescents with BRAF V600 mutated tumours (type of cancer with a specific type of gene mutation, called BRAF V600 mutation). Dabrafenib is a drug approved by the FDA for treatment of metastatic melanoma (type of skin cancer) in adults with the BRAF V600 mutation.

  This study consists of 3 parts.
  Part A: Dose escalation phase: Participants <2 years of age will not be included in this phase.

  Dose levels to be tested:
  Dose Level 1 – (starting dose): 0.0125 mg/kg/day
  Dose Level 2 – 0.025 mg/kg/day
  Dose Level 3 – 0.04 mg/kg/day
  Depending on the study data, GSK may amend the protocol to add a higher dose.

  Age expansion phase: Additional participants will be enrolled in 3 age groups: 1 month to < 2 years, 2-12 years, and >12-<18 years of age (participant cannot be 18 years of age) and receive trametinib at the dose that was well tolerated in the dose escalation phase.

  Part B: Participants will be enrolled in one of the following groups depending on their type of cancer and will receive the dose identified as being well-tolerated in part A:
  • Neuroblastoma
  • Low grade glioma
  • Neurofibromatosis Type 1 associated plexiform neurofibromas
  • BRAF V600 mutated tumours

  Part C: Combination of trametinib and dabrafenib in treatment of cancer in children and adolescents with BRAF V600 mutated tumours will be studied.

  Approximately 94 participants (36 in Part A, 40 in Part B, and 18 in Part C) in approximately 5 countries world-wide will be enrolled.

• REC name

  South Central - Berkshire B Research Ethics Committee

• REC reference

  15/SC/0679

• Date of REC Opinion

  15 Dec 2015

• REC opinion

  Further Information Favourable Opinion