Liposome-encapsulated Irinotecan Hydrochloride PEP02 or Irinotecan Hydrochloride, Leucovorin Calcium, and Fluorouracil as Second-Line Therapy in Treating Patients With Metastatic Colorectal Cancer (PEPCOL)
Colorectal Cancer
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring adenocarcinoma of the colon, recurrent colon cancer, stage IV colon cancer, adenocarcinoma of the rectum, recurrent rectal cancer, stage IV rectal cancer
Eligibility Criteria
DISEASE CHARACTERISTICS
Histologically proven adenocarcinoma of colon or rectum
- Metastatic disease, exclusive of bone metastasis
- Not suitable for complete carcinological surgical resection
- Patients regardless KRAS status (wild type or mutated) or previous anti EGFR treatment or not.
- Measurable lesion (greater than 1 cm) as assessed by CT scan or MRI according to RECIST criteria (version 1.1)
- Must have received prior oxaliplatin-based chemotherapy for metastatic disease
- No symptomatic ascites or pleural effusion not evacuated prior to study entry
- No history or evidence of CNS metastasis
PATIENT CHARACTERISTICS:
- WHO or ECOG performance status 0-2
- Absolute neutrophil count greater than 1500 per mm3
- Platelet count greater than 100 000 per microL
- Hemoglobin greater than 9 g per dL (may be transfused to maintain or exceed this level)
- INR less or equal than 1.5. aPTT less than 1.5 ULN (exemption:patients on full anticoagulation due to VTE must have an in-range INR.
- Serum creatinine less than 150 micromol per L
- Calculated creatinine clearance greater than 30 mL per min
- Total bilirubin less than 1.5 times upper limit of normal
- Proteinuria less than 2 plus (dipstick urinalysis) or less than 1 g per 24 hours.
- Negative serum pregnancy test
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No severe arterial thromboembolic events within the past 6 months, including myocardial infarction and stroke
- No baseline diarrhea greater than grade 1
- No total or partial bowel obstruction
- No uncontrolled hypercalcemia
- No uncontrolled hypertension, or history of hypertensive crisis, or hypertensive encephalopathy
- No other prior or concurrent malignancy, except adequately treated in situ carcinoma of the uterine cervix, basal cell or squamous cell carcinoma of the skin, or cancer in complete remission for more than 5 years
- No other serious and uncontrolled non-malignant disease
- Major surgery or traumatic injury within the last 28 days.
- No known allergy to any excipients of study drugs
- Must be registered in a national health care system (CMU included)
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Prior anti-EGFR therapy allowed
- No prior irinotecan hydrochloride
- No concurrent agents known to have anticancer activity
- No concurrent radiotherapy
- No participation in another clinical trial with any investigational drug or treatments concurrently or within the past 30 days
Sites / Locations
- Hopital Saint Antoine
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
FOLFIRI 1 or m FOLFIRI3-Bevacizumab
FUPEP-Bevacizumab
FOLFIRI 1-Bevacizumab: Day 1 H0 : Bevacizumab 5 mg/kg, 30-90 min infusion H+1: Irinotecan 180 mg/m² in 250 ml NaCl 0.9%, 1h infusion Folinic Acid 400 mg/m² (l + d racemic form, or l form 200 mg/m²) over 2h H + 3: 5-FU bolus 400 mg/m², 15 min infusion H + 3.5: 5-FU continuous infusion 2400 mg/m² 46-h infusion End of cycle: day 14 modified FOLFIRI3-Bevacizumab H0 :Bevacizumab 5 mg/kg, 30-90 min infusion H+1:Irinotecan 90 mg/m² in 250 ml NaCl 0.9%, 1h infusion H+1: Folinic Acid 400 mg/m² (l + d racemic form, or l form 200 mg/m²) 2-h infusion H + 3: 5-FU continuous infusion 2400 mg/m² 46-h infusion Day 3 (H+49) H0 Irinotecan 90 mg/m² in 250 ml NaCl 0.9%, 1h infusion End of cycle: day 14
Day 1 H0 :Bevacizumab 5 mg/kg, 30-90 min infusion H +1 :PEP02 80 mg/m² , 1h30 infusion. The infusion time could be reduced to 1h from cycle 2 if no acute infusion reaction has occured in cycle 1. H +1 : Folinic Acid 400 mg/m² (l + d racemic form, or l form 200 mg/m²) , 2-h infusion H +3 : 5-FU continuous infusion 2400 mg/m² 46-h infusion End of cycle: day 14