Phase 2 study of RO5083945 in patients with colorectal cancer Version1

• Research type

  Research Study

• Full title

  A randomized, multicenter, open-label phase II study of RO5083945 in combination with FOLFIRI versus FOLFIRI plus cetuximab or FOLFIRI alone as second line treatment in patients with KRAS wild-type or mutant metastatic colorectal cancer.

• IRAS ID

  68927

• Contact name

  James Cassidy

• Sponsor organisation

  F. Hoffmann-La Roche Ltd

• Eudract number

  2010-022983-11

• Research summary

  Colorectal cancer is one of the most frequent types of cancer worldwide with a mortality rate of 50%. One of the key genetic steps in developing this cancer can include the activation of the oncogene KRAS, which occurs in 37% of colorectal cancer patients. The currently available treatments include flurouracil (5-FU), which has increased the median survival to more than 20 months. 5-FU can also be used in combination with leucovorin. Irinotecan and oxaliplatin are also used in first-line treatment and combination names FOLFIRI and FOLFOX are widely used. In addition, capecitabine is used in combination with irinotecan or oxaliplatin.Two classes of monoclonal antibodies have been approved for use in CRC: the anti-vascular endothelial growth factor (VEGF) receptor antibody bevacizumab and the anti-epidermal growth factor receptor (EGFR) antibodies cetuximab and panitumumab. RO5083945 is a recombinant humanized and glycoenginered anti-Epidermal Growth Factor Receptor (EGFR/HER1) monoclonal antibody (mAB). There are 2 ongoing Phase I/II clinical studies using RO5083945, BO21945 and BP22350. BO21945 is a phase I study in patients with solid tumours and an expansion phase with KRAS mutant colorectal cancer. BP22350 is a mode of action study for patients with head and neck cancer. As of 17 Aug 2010, 113 patients have received RO5083945 by IV infusion at doses between 50 and 1400mg. In Study BO21945, it has been shown that in 31 patients with CRC (11 KRAS wild type and 20 KRAS mutant), RO5083945 is active in KRAS mutant CRC patients with 10 KRAS mutant patients achieving stable disease and 1 KRAS mutant patient achieving partial response.RO5083945 generally well tolerated with the majority of the adverse events being mild or moderate. This study is a randomised, phase II open label study and patients will be randomised based on the KRAS status in the fresh (new) tumour biopsy obtained during screening. 160 patients will be enrolled into the study with 80 being in KRAS WT group and 80 being in KRAS mutant group.Participants may remain on treatment until their disease progresses. Study procedures include a fresh (new) tumour biopsy, archival tumour biopsy, CT/MRI scans, physical exams, vital signs, blood and urine testing, ECGs, pregnancy testing for females and a physician completed skin toxicity questionnaireF. Hoffman-La Roche Ltd is the sponsor of the clinical trial.

• REC name

  East of Scotland Research Ethics Service REC 2

• REC reference

  10/S0501/67

• Date of REC Opinion

  24 Jan 2011

• REC opinion

  Favourable Opinion