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GROUP A (Patients with unresectable advanced non-colorectal cancer ) - irinotecan + MM-398 dose escalation (3-18 patients)

Level 1 : initial DOUBLIRI dose 60/90 (0-3 patients)

* MM-398 : 60mg/m²
* Irinotecan (CPT-11) : 90mg/m²

Level 2: DOUBLIRI dose 80/90 (9 - 18 patients)

* MM-398 : 80mg/m²
* CPT-11: 90mg/m²

Level 3A: DOUBLIRI dose 60/120 (12-18 patients)

* MM-398 : 60mg/m²
* CPT-11: 120mg/m²

Level 3B: DOUBLIRI dose : 80/120 (12-18 patients)

* MM-398 : 80mg/m²
* CPT-11 : 120 mg/m²

GROUP B (Patients with unresectable metastatic colorectal cancer)- LV/5FU-bevacizumab+irinotecan+MM-398 dose Escalation (3-18 patients)

same level as group A + LV/5FU - bevacizumab regimen :

* Bevacizumab : 5mg/kg(day (d) 1)
* Leucovorin (LV) : 400mg/m² (d1)
* 5-fluorouracile infusion (5 FU) :2400mg/m² (d1,2)

unresectable Advanced non-colorectal cancer

MM-398

unresectable metastatic colorectal cancer

Leucovorin (LV)

5-fluorouracile (5-FU)

bevacizumab

Benoist Chibaudel, MD

MM-398 (also known as PEP02) is nanoliposomal encapsulated irinotecan: the liposomal formulation is designed to extend plasma circulation and to increase accumulation in the tumor through the enhanced permeability and retention (EPR) effect.

This study introduces a new concept of combining free and nanoliposomal drugs.

This is a dose-finding and therapeutic exploratory phase Ib multi-center, open label study of MM-398 plus irinotecan in two different settings:

* Group A : patients with unresectable advanced non-colorectal cancer who should receive only MM-398 and irinotecan
* Group B : patients with unresectable metastatic colorectal cancer who should receive MM-398 and irinotecan combined with leucovorin, 5-fluorouracil and bevacizumab.

These groups will be enrolling in parallel. Pharmacokinetic and biomarker sampling will also be performed.

There are three periods to this study :

Screening period (up to -28d): patients undergo screening assessments to determine the eligibility for the study

MM-398 treatment period (C1D1 until safety evaluation/progression): patients receive treatment every 2 weeks and undergo biopsies and other required assessments. The treatment period is divided into a maximum of 3 dose levels

Follow up period: patients will be followed-up 30 days after their last dose of MM-398 for final safety assessments, and every 2 months thereafter for overall survival follow-up

A Dose Escalation Study of MM-398 Plus Irinotecan in Patients With Unresectable Advanced Cancer

A Phase Ib Dose Escalation Study of MM-398 Plus Irinotecan in Patients With Unresectable Advanced Cancer - DOUBLIRI

to determine the levels of MM-398/irinotecan, SN-38 and SN-38G

Merrimack Pharmaceuticals

GERCOR - Multidisciplinary Oncology Cooperative Group

Spots Global Cancer Trial Database for non colorectal