Trial of FOLF(HA)Iri Versus FOLFIRI in mCRC

Study Overview
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Brief Summary
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Trial design: Phase III, FOLFIRI versus FOLF(HA)iri (the FOLFIRI regimen with Hyaluronic acid-Irinotecan or HA-Irinotecan) regimen. Patients with mCRC (metastatic colorectal cancer), 2nd/3rd line irinotecan naïve. Randomized 1:1, double-blinded, multi-centre, multi-national (Australia, Bulgaria, Poland, Serbia, Russia, Ukraine and the United Kingdom). Dosing regimen: Irinotecan (180 mg/m2) or HA-Irinotecan (180 mg/m2), IV, over 90 minutes, day 1 (in patients > 75 years of age, the irinotecan and HA-Irinotecan dose in must be reduced to 150 mg/m2). Leucovorin, 400 mg/m2, or levoleucovorin, 200 mg/m2, IV over 90 minutes with irinotecan. 5-fluorouracil (5-FU), 400 mg/m2 IV bolus day 1, then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) continuous infusion. Repeat every 2 weeks for 8 months. Patient accrual over approximately 12-14 months. Monitoring to 18 months post-randomization. 390 patients. Progression Free Survival (PFS) primary endpoint. Safety analysis on the initial 20 patients.

Official Title
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Randomized Double-blind Phase III Trial of FOLF(HA)Iri vs FOLFIRI for Second or Third Line Therapy in Irinotecan-naïve Patients With Metastatic Colorectal Cancer

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Irintoecan
* Drug: HA-Irinotecan solution for Infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic colorectal cancer with disease progression after first or second line chemotherapy Irinotecan naïve. ECOG performance status of 0 or 1. Measurable disease, i.e. at least one measurable metastatic lesion (spiral CT or MRI). Histological proof of colorectal cancer. 18 years of age and older. Adequately recovered from and at least 4 weeks after recent surgery or chemotherapy. Women of child-bearing potential (WOCBP) and male partners of WOCBP must agree to use adequate contraception. Patient consent obtained and signed according to local and/or national ethics. CT or MRI scan of chest/abdomen/pelvis within 21 days prior to randomization. Hematology done within 14 days prior to randomization. Chemistry done within 14 days prior to randomization. Exclusion Criteria: History of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for > 5 years. Locally advanced or recurrent disease only. Unsuitability for irinotecan including known Gilbert's syndrome, active inflammatory bowel disease or chronic diarrhea greater than or equal to grade 2. Abdominal or pelvic radiation therapy within the last 12 months. Women who are pregnant or breastfeeding. Any condition (e.g., psychological, geographical) that would render the protocol treatment dangerous. Significant cardiac disease. Untreated or symptomatic brain or central nervous system (CNS). Presence of pleural effusion or ascites requiring therapeutic thoracocentesis or paracentesis. Current partial or complete bowel obstruction. Concomitant active infection. Enrolled in any other investigational trial, unless treatment in that trial has been discontinued at least 30 days prior to signing the Informed Consent for the ACO-002 study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: FOLFIRI<br> | Drug: Irintoecan<br>* Irinotecan, 180 mg/m2 IV, over 90 minutes, day 1 (in patients > 75 years of age, the irinotecan dose in must be reduced to 150 mg/m2). Leucovorin, 400 mg/m2, or levoleucovorin, 200 mg/m2, IV over 90 minutes with irinotecan. 5-FU, 400 mg/m2 IV bolus day 1, then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) continuous infusion. Repeat every two weeks. 8 months of treatment.<br>|
| Experimental: FOLF(HA)iri<br> | Drug: HA-Irinotecan solution for Infusion<br>* HA-Irinotecan (irinotecan 180 mg/m2), IV, over 90 minutes, day 1 (in patients > 75 years of age, the irinotecan dose in must be reduced to 150 mg/m2). Leucovorin, 400 mg/m2, or levoleucovorin, 200 mg/m2, IV over 90 minutes with irinotecan. 5-FU, 400 mg/m2 IV bolus day 1, then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) continuous infusion. Repeat every two weeks 8 months of treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) |  | Approximately 20 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | Diarrhea and haematology | After initial 20 patients receive 2 cycles, then 6 monthly thereafter. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mCRC, CRC, colorectal, irinotecan, Hyaluronic acid, Hyaluronan