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| ID | Type | Description | Link |
|---|---|---|---|
| FRE-GERCOR-PEPCOL-C10-1 | |||
| EU-21115 | |||
| EUDRACT-2010-020468-39 | |||
| PHARMAENGINE-FRE-GERCOR-PEPCOL |
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efficacy interim analysis as per protocol
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RATIONALE: Drugs used in chemotherapy, such as liposome-encapsulated irinotecan hydrochloride PEP02, irinotecan hydrochloride, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving liposome-encapsulated irinotecan hydrochloride PEP02 together with leucovorin calcium and fluorouracil is more effective than giving irinotecan hydrochloride together with leucovorin calcium and fluorouracil as second-line therapy in treating patients with metastatic colorectal cancer.
PURPOSE: This randomized phase II trial is studying liposome-encapsulated irinotecan hydrochloride PEP02 given together with leucovorin calcium and fluorouracil to see how well it works compared with giving irinotecan hydrochloride together with leucovorin calcium and fluorouracil as second-line therapy in treating patients with metastatic colorectal cancer.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter study. Patients are stratified, in terms of prognosis, according to treatment center, prognostic score (ECOG performance status [PS] 0 and normal LDH value vs ECOG PS > 1 and/or LDH > 1 times upper limit of normal), and time to progression after first-line therapy (≥ 9 months vs < 9 months). Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients are assigned to either the FOLFIRI 1 or Modified FOLFIRI 3 treatment groups according to the investigator's discretion in combination with bevacizumab
Arm II (FUPEP)in combination with bevacizumab: Patients receive bevacizumab over 30-90 minutes liposome-encapsulated irinotecan hydrochloride PEP02 IV over 60-90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically for pharmacogenetic analysis of UGT1A family polymorphisms. Quality of life is assessed by using a generic scale EQ-5D and the QLQ-C30 questionnaire at baseline and after courses 4 and 8.
After completion of study treatment, patients are followed up at day 30 and then every 2-3 months thereafter.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| FOLFIRI 1 or m FOLFIRI3-Bevacizumab | Active Comparator | 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 |
|
| FUPEP-Bevacizumab | Experimental | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FOLFIRI 1-Bevacizumab | Drug |
| ||
| fluorouracil |
| Measure | Description | Time Frame |
|---|---|---|
| Tumor response | Assessment of tumor response at 2 month after randomization by RECIST 1.1 | at 2 months |
| Measure | Description | Time Frame |
|---|---|---|
| Safety | assessment of adverse events and toxicity according NCI CTC v4.0 | before each 2-weeks cycles |
| Progression-free survival | the time from the date of randomization to the date of progressive disease (RECIST criteria) or death (any cause) |
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DISEASE CHARACTERISTICS
Histologically proven adenocarcinoma of colon or rectum
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:
PRIOR CONCURRENT THERAPY:
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| Name | Affiliation | Role |
|---|---|---|
| Frederique Maindrault-Goebel, MD | Hopital Saint Antoine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hopital Saint Antoine | Paris | 75012 | France |
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| Drug |
|
| irinotecan hydrochloride | Drug |
|
| leucovorin calcium | Drug |
|
| liposome-encapsulated irinotecan hydrochloride PEP02 | Drug |
|
| Bevacizumab | Drug |
|
| Overall survival | from the date of randomization to the date of patient death, due to any cause, or to the last date the patient was known to be alive |
| Quality of life | Quality of life will be assessed by using a generic scale EQ-5D and the QLQ-C30 questionnaire | at baseline, cycle 4, and cycle 8 |
| Correlation of UGT1A family polymorphism and the toxicity of liposome-encapsulated irinotecan hydrochloride PEP02 or irinotecan hydrochloride | at baseline |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D003110 | Colonic Neoplasms |
| D012004 | Rectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
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| ID | Term |
|---|---|
| D005472 | Fluorouracil |
| D000077146 | Irinotecan |
| D002955 | Leucovorin |
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D002166 | Camptothecin |
| D000470 | Alkaloids |
| D005575 | Formyltetrahydrofolates |
| D013763 | Tetrahydrofolates |
| D005492 | Folic Acid |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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