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

This study has suspended participant recruitment.
(efficacy interim analysis as per protocol)
Sponsor:
Information provided by (Responsible Party):
Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
ClinicalTrials.gov Identifier:
NCT01375816
First received: June 16, 2011
Last updated: November 14, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Drug: FOLFIRI 1-Bevacizumab
Drug: fluorouracil
Drug: irinotecan hydrochloride
Drug: leucovorin calcium
Drug: liposome-encapsulated irinotecan hydrochloride PEP02
Drug: Bevacizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of PEP02 or Irinotecan in Combination With Leucovorin and 5-Fluorouracil in Second Line Therapy of Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR):

Primary Outcome Measures:
  • Tumor response [ Time Frame: at 2 months ] [ Designated as safety issue: No ]
    Assessment of tumor response at 2 month after randomization by RECIST 1.1


Secondary Outcome Measures:
  • Safety [ Time Frame: before each 2-weeks cycles ] [ Designated as safety issue: Yes ]
    assessment of adverse events and toxicity according NCI CTC v4.0

  • Progression-free survival [ Time Frame: the time from the date of randomization to the date of progressive disease (RECIST criteria) or death (any cause) ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: at baseline, cycle 4, and cycle 8 ] [ Designated as safety issue: No ]
    Quality of life will be assessed by using a generic scale EQ-5D and the QLQ-C30 questionnaire

  • Correlation of UGT1A family polymorphism and the toxicity of liposome-encapsulated irinotecan hydrochloride PEP02 or irinotecan hydrochloride [ Time Frame: at baseline ] [ Designated as safety issue: No ]

Enrollment: 55
Study Start Date: May 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: FOLFIRI 1 or m FOLFIRI3-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

Drug: FOLFIRI 1-Bevacizumab Drug: fluorouracil Drug: irinotecan hydrochloride Drug: leucovorin calcium Drug: Bevacizumab
Experimental: FUPEP-Bevacizumab

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

Detailed Description:

OBJECTIVES:

Primary

  • To evaluate the objective response rates (complete response and partial response) in patients with metastatic colorectal cancer treated with liposome-encapsulated irinotecan hydrochloride PEP02, leucovorin calcium, and fluorouracil (FUPEP) Versus irinotecan hydrochloride, leucovorin calcium, and fluorouracil (FOLFIRI 1) or leucovorin calcium, fluorouracil, and irinotecan hydrochloride-modified (FOLFIRI 3-modified).

Secondary

  • To determine the safety of these regimens in these patients.
  • To determine progression-free survival of these patients.
  • To determine overall survival of these patients.
  • To assess the quality of life of these patients.
  • To assess the correlation of UGT1A family polymorphism and the toxicity of liposome-encapsulated irinotecan hydrochloride PEP02 or irinotecan hydrochloride.

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

    • FOLFIRI 1 in combination with bevacizumab: Patients receive bevacizumab over 30-90 minutes,irinotecan hydrochloride over 1 hour and leucovorin calcium IV over 2 hours on day 1 and a bolus of fluorouracil followed by fluorouracil IV over 46 hours beginning on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity
    • Modified FOLFIRI 3 in combination with bevacizumab: Patients receive bevacizumab,irinotecan hydrochloride, leucovorin calcium, and fluorouracil as in FOLFIRI 1. Patients also receive irinotecan hydrochloride IV over 1 hour on day 3. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
  • 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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01375816

Locations
France
Hopital Saint Antoine
Paris, France, 75012
Sponsors and Collaborators
Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
Investigators
Principal Investigator: Frederique Maindrault-Goebel, MD Hopital Saint Antoine
  More Information

Additional Information:
No publications provided

Responsible Party: Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
ClinicalTrials.gov Identifier: NCT01375816     History of Changes
Other Study ID Numbers: CDR0000701454, FRE-GERCOR-PEPCOL-C10-1, EU-21115, EUDRACT-2010-020468-39, PHARMAENGINE-FRE-GERCOR-PEPCOL
Study First Received: June 16, 2011
Last Updated: November 14, 2013
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
France: National Consultative Ethics Committee for Health and Life Sciences

Keywords provided by Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR):
adenocarcinoma of the colon
recurrent colon cancer
stage IV colon cancer
adenocarcinoma of the rectum
recurrent rectal cancer
stage IV rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Irinotecan
Bevacizumab
Camptothecin
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on April 23, 2014