COMBI-AD. COMBInation study in treatment of ADjuvant melanoma

• Research type

  Research Study

• Full title

  COMBI-AD: A phase III randomized double blind study of dabrafenib (GSK2118436) in COMBInation with trametinib (GSK1120212) versus two placebos in the ADjuvant treatment of high-risk BRAF V600 mutation-positive melanoma after surgical resection.

• IRAS ID

  113351

• Contact name

  Paul Nathan

• Sponsor organisation

  Novartis Pharmaceuticals UK Limited

• Eudract number

  2012-001266-15

• Clinicaltrials.gov Identifier

  113,557, IND

• Duration of Study in the UK

  20 years, 3 months, 4 days

• Research summary

  Cutaneous melanoma is the most aggressive of all skin cancers. Although representing only 4% of all cancers, of the 132,000 people diagnosed globally each year, 37,000 will die.50% of cutaneous melanomas demonstrate a BRAF V600E/K mutation.
  Surgery is the preferred treatment for localised melanoma and frequently cures early stage disease. Patients with lymph node involvement are at high risk of relapse after definitive surgery. Around half of all these patients will ultimately die of metastatic disease ( cancer that has spread from where it started). In the adjuvant setting , where additional cancer treatment is given after surgery to lower the risk of the cancer coming back, options are limited. Many agents have shown little or no benefit. The National Comprehensive Cancer Network guidelines recommend clinical trials, observation and interferon as the 3 therapy options with clinical trials preferred. High-dose interferon, the only approved therapy is not widely accepted as standard of care due to a questionable survival benefit, high incidence of serious toxicities & negligible benefit for patients with bulkier disease. Therefore there is an unmet need for more effective therapies with an acceptable safety profile in the adjuvant setting. This study will compare the combination of dabrafenib (B-RAF inhibitor) plus trametinib (MEK inhibitor ) with placebo ( or dummy treatment) in patients with the BRAF V600 mutation. After Informed Consent, patients’ tumour tissue will be tested for the V600 BRAF mutation . Approx 852 subjects (55 in the UK) will be randomised in a 1:1 ratio to receive either dabrafenib and trametinib combination therapy or two matching placebos for 12 months to investigate how much longer the combination may delay relapse. Neither Investigators nor patients will know which treatment they are receiving. Patients will also be followed for survival.

• REC name

  South West - Central Bristol Research Ethics Committee

• REC reference

  12/SW/0361

• Date of REC Opinion

  21 Jan 2013

• REC opinion

  Further Information Favourable Opinion