Liposome-encapsulated Irinotecan Hydrochloride PEP02 or Irinotecan Hydrochloride, Leucovorin Calcium, and Fluorouracil as Second-Line Therapy in Treating Patients With Metastatic Colorectal Cancer

NCT01375816 | Terminated Phase 2 DMC

• 5 other identifiers: CDR0000701454FRE-GERCOR-PEPCOL-C10-1EU-21115EUDRACT-2010-020468-39PHARMAENGINE-FRE-GERCOR-PEPCOL
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colorectal Cancer

Keywords

adenocarcinoma of the colon; recurrent colon cancer; stage IV colon cancer; adenocarcinoma of the rectum; recurrent rectal cancer; stage IV rectal cancer

Outcome Measures

Primary Outcomes (1)

• Tumor response

  Assessment of tumor response at 2 month after randomization by RECIST 1.1

  at 2 months

Secondary Outcomes (5)

• Safety

  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)

• 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

  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

Study Arms (2)

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

Drug: FOLFIRI 1-Bevacizumab; Drug: fluorouracil; Drug: irinotecan hydrochloride; Drug: leucovorin calcium; Drug: Bevacizumab

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

Drug: fluorouracil; Drug: leucovorin calcium; Drug: liposome-encapsulated irinotecan hydrochloride PEP02; Drug: Bevacizumab

Interventions

FOLFIRI 1-Bevacizumab DRUG

FOLFIRI 1 or m FOLFIRI3-Bevacizumab

fluorouracil DRUG

FOLFIRI 1 or m FOLFIRI3-Bevacizumab; FUPEP-Bevacizumab

irinotecan hydrochloride DRUG

FOLFIRI 1 or m FOLFIRI3-Bevacizumab

leucovorin calcium DRUG

FOLFIRI 1 or m FOLFIRI3-Bevacizumab; FUPEP-Bevacizumab

liposome-encapsulated irinotecan hydrochloride PEP02 DRUG

FUPEP-Bevacizumab

Bevacizumab DRUG

FOLFIRI 1 or m FOLFIRI3-Bevacizumab; FUPEP-Bevacizumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• GERCOR - Multidisciplinary Oncology Cooperative Group: lead

Study Sites (1)

Hopital Saint Antoine

Paris, 75012, France

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Fluorouracil; Irinotecan; Leucovorin; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Frederique Maindrault-Goebel, MD

  Hopital Saint Antoine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2011
• First Posted: June 17, 2011
• Study Start: May 1, 2011
• Primary Completion: June 1, 2014
• Study Completion: December 1, 2014
• Last Updated: June 4, 2015

Record last verified: 2013-11

Locations

FR (1)