|Full title:||A Phase II, multicenter, open-label, randomized study evaluating the efficacy and safety of FOLFIRI +MEHD7945A versus FOLFIRI +CETUXIMAB in second line in patients with KRAS wild-type metastatic colorectal cancer|
|Cancer type:||Metastatic colorectal|
|Study GO28074 is an open-label, randomized, global, multicenter, Phase II trial designed to estimate the efficacy of MEHD7945A when combined with FOLFIRI chemotherapy in patients with KRAS wild-type metastatic colorectal cancer (mCRC) who have progressed on or after first-line oxaliplatin-containing chemotherapy for metastatic disease. Patients with KRAS wild-type tumors will be identified by the investigator using local assessment of KRAS mutation status; no central confirmation is required prior to enrollment. Eligible patients will be randomized in a 1:1 ratio to one of two treatment arms.
• Arm A (experimental arm): FOLFIRI +MEHD7945A
Study treatment will be given in cycles repeated every 14 days and will consist of FOLFIRI +MEHD7945A (Arm A) or FOLFIRI + cetuximab (Arm B). Patients in Arm A will receive MEHD7945A at a fixed dose of 1100 mg IV q2w (every cycle), starting on Day 1 of Cycle 1. Patients in Arm B will receive cetuximab administered according to the Erbitux prescribing information, with a loading dose of 400 mg/m2 IV on Day 1 of Cycle 1, followed by weekly doses of 250 mg/m2 IV (2 × per cycle). FOLFIRI chemotherapy will be administered q2w (every cycle) starting on Day 1 of Cycle 1.
FOLFIRI consists of irinotecan (starting dose of 180 mg/m2), 5-FU (starting bolus and 46-hour infusional doses of 400 mg/m2 and 2400 mg/m2, respectively), and leucovorin (racemic, starting dose of 400 mg/m2 or L-form, starting dose of 200 mg/m2). FOLFIRI and MEHD7945A or cetuximab will be administered until disease progression or unacceptable toxicity. If a patient stops FOLFIRI either in part or in whole, they should continue on MEHD7945A or cetuximab until documented disease progression or unacceptable toxicity. Similarly, if a patient stops cetuximab or MEHD7945A for unacceptable toxicity, they should continue FOLFIRI either in part or in whole until documented disease progression or unacceptable toxicity.
Randomization will be stratified across the treatment arms by the following predefined stratification variables: disease progression within 6 months of completing or discontinuing first-line prior oxaliplatin-containing chemotherapy (yes vs. no) and prior therapy with bevacizumab (yes vs. no). While the safety of MEHD7945A as a single agent has been demonstrated in Phase I and has been shown to be generally consistent with that of approved anti-EGFR therapies without identification of new safety events, the safety of combined therapy with MEHD7945A and FOLFIRI has not been previously studied. An early interim safety analysis will be conducted and overseen by an internal monitoring committee. Efficacy assessments will be performed every 8 weeks from the time of study treatment initiation until disease progression. Upon progression, patients with tumour lesions that in the opinion of the investigator can be safely biopsied should be asked to undergo an optional biopsy of their tumour.
After discontinuation from study treatment, patients will be followed for survival every 3 months until death, loss to follow up, or study termination by the Sponsor.
|Sites:||Auckland (CTNZ acting as a site)|
|Lead Investigator:||Professor Michael Findlay|
|Contact:||Lindsey Wylde (firstname.lastname@example.org)|
|Trial Registry reference:||NCT01652482 (click for more details)|