Conditions: Colon Cancer Rectal Cancer
Keywords: locally advanced metastatic colon rectal cancer
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 82
Healthy volunteers: no

Brief summary:
The purpose of the Phase Ib portion is to find out the highest dose of study drug that can safely be given when tested in a small group of subjects.

The purpose of the Phase II portion is to find out how safe the study drug is when taken at the highest dose in a larger group of subjects.

Detailed description:
This open-label, multicenter, randomized study will consist of a Phase Ib portion: a safety run-in period with 3 ascending doses of E7820; and a Phase II portion: a randomized 2-arm design. Approximately 95 patients with measurable, nonresectable locally advanced or metastatic colorectal adenocarcinoma, who have failed first-line chemotherapy, will be enrolled in the study (approximately 12 to 15 patients in the Phase Ib portion and 80 patients in the Phase II portion). Patients will only participate in either the Phase Ib or the Phase II portion of the study. Patients will receive up to a planned total of 12 cycles of study treatment unless there is occurrence of progressive disease, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurs first. After 12 cycles, patients who demonstrate clinical benefit may continue single agent E7820 for long as clinical benefit is sustained and the treatment is well tolerated. If the treating physician does not feel comfortable discontinuing chemotherapy after 12 cycles, further chemotherapy may be considered following discussion with the medical monitor and sponsor.

Arms:
arm 1: Experimental Irinotecan plus E7820 arm 2: FOLFIRI alone

Interventions: intervention 1: FOLFIRI intervention 2: E7820
Intervention descriptions: intervention 1: Comparator dose and mode of administration The FOLFIRI regimen consists of irinotecan at 180 mg/m2 (IV infusion) on Day 1 of each 14-day cycle, leucovorin at 200 mg/m2 (400 mg/m2 if using d,l-racemic mixture of leucovorin) by IV infusion on Day 1 of each cycle, and 5-FU at 400 mg/m2 as an IV bolus injection followed by a total of 2400 mg/m2 by continuous IV infusion over 46 hours over Days 1 and 2 via an ambulatory programmable pump (the use of an ambulatory pump is optional). intervention 2: Test product: dose and mode of administration:

E7820 is administered orally in tablet form once daily, every day of each 14-day treatment cycle. For the Phase Ib portion, the doses will be 40 mg/day, 70 mg/day, and 100 mg/day, and for the Pase II portion, the dose will be the MTD in combination with Irinotecan, as determined during the Phase ib portion of the study.

The irinotecan regimen consists of an irinotecan dose of 180 mg/m2 by IV infusion once every 2 weeks (Day 1 of each 14-day cycle).

Protocol document: