FOLF(HA)iri: Trial of FOLF(HA)Iri Versus FOLFIRI in mCRC

Sponsor

Alchemia Oncology (Industry)

Overall Status

Unknown status

CT.gov ID

NCT01290783

Collaborator

(none)

390

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Colorectal Cancer	Drug: Irintoecan Drug: HA-Irinotecan solution for Infusion	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

390 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2011

Actual Primary Completion Date :

Oct 1, 2014

Anticipated Study Completion Date :

Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: FOLFIRI	Drug: Irintoecan 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.
Experimental: FOLF(HA)iri	Drug: HA-Irinotecan solution for Infusion 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.

Arm

Intervention/Treatment

Active Comparator: FOLFIRI

Drug: Irintoecan

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.

Experimental: FOLF(HA)iri

Drug: HA-Irinotecan solution for Infusion

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.

Outcome Measures

Primary Outcome Measures

Progression Free Survival (PFS) [Approximately 20 months]

Secondary Outcome Measures

Safety [After initial 20 patients receive 2 cycles, then 6 monthly thereafter.]
Diarrhea and haematology

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Southern Medical Day Care Centre	Wollongong	New South Wales	Australia	2500
2	Western General Hospital	Melbourne	Victoria	Australia	3011
3	Royal Melbourne Hospital	Melbourne	Victoria	Australia	3050
4	Monash Medical Centre	Melbourne	Victoria	Australia	3165
5	Border Medical Oncology	Wodonga	Victoria	Australia	3690