MK0646-025 :A Phase 2 comparative study in metastatic Rectal cancer

• Research type

  Research Study

• Full title

  A Phase IIA Open Label, Adaptive, Randomized Clinical Trial of Dalotuzumab (MK-0646) Treatment in Combination with Irinotecan Versus Cetuximab and Irinotecan for Patients with Metastatic Rectal Cancers(mRC) Expressing High IGF-1,Low IGF-2 Levels.

• IRAS ID

  103263

• Contact name

  David Watkins

• Sponsor organisation

  Merck Sharpe & Dohme

• Eudract number

  2012-000317-36

• ISRCTN Number

  na

• Research summary

  This randomised study will evaluate the patient outcomes achieved with the combination of dalotuzumab and irinotecan, as compared to the current standard of care (cetuximab and irinotecan) in a selected sub-group (high IGF-1 & low IGF-2) of patients with metastatic KRAS wild-type chemorefractory recal cancer. Dalotuzumab is an antibody agent that targets the insulin-like growth factor receptor (IGF1R). Activation of the insulin-like growth factor receptor can occur by binding of its cognate ligand; IGF-1. This study is designed to assess if Dalotuzumab is more active than cetuximab when given to patients with rectal cancers which express high levels of the IGF-1 protein. Approximately 70 patients will be randomised into the study, 35 patients per arm. Arm A: Irinotecan 180mg/m2 every two weeks Dalotuzumab 10mg/kg weekly. Arm B: Irinotecan 180mg/m2 every two weeks Cetuximab weekly (initial dose 400mg/m2) followed by 250mg/m2. When 36 patients have completed 6 weeks of treatment enrollment will stop and an interim analysis will be performed (futility test). The analysis will compare the proportion of patients in each arm that have achieved a reduction in tumour volume (response) or developed worsening disease (progression-free survival). If futility is not declared the study will continue to enrol approximately 34 additional patients. A further analysis will be undertaken when a total of 42 progression-free survival events (defined as patients developing worsening disease or death) have occurred. Patients in Arm A who develop disease progression whilst on the study will be able to receive Irinotecan and Cetuximab (standard of care) according to local standard NHS practice. An indepedent committee (IDMC) will review the results during the course of the study to ensure the potential for harm to patients is minimised. Subjects will participate in this study for a maximum of approximately 24 months (assumption treatment 9 months).

• REC name

  South Central - Oxford B Research Ethics Committee

• REC reference

  12/SC/0310

• Date of REC Opinion

  20 Jul 2012

• REC opinion

  Further Information Favourable Opinion