A Randomized Phase II Study of PEP02 or Irinotecan in Combination With Leucovorin and 5-Flourouracil in Second Line Therapy of Metastatic Colorectal Cancer
18 Years
75 Years
Both
Colorectal Cancer
Trial Information
A Randomized Phase II Study of PEP02 or Irinotecan in Combination With Leucovorin and 5-Flourouracil in Second Line Therapy of Metastatic Colorectal Cancer
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.
- FOLFIRI 1: Patients receive 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: Patients receive 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): Patients receive 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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically proven adenocarcinoma of colon or rectum
- Metastatic disease, exclusive of bone metastasis
- Not suitable for complete carcinological surgical resection
- Any KRAS status allowed (wild type or mutated)
- Measurable lesion (≥ 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 ≥ 1,500/mm^3
- Platelet count ≥ 100,000/μL
- Hemoglobin ≥ 9 g/dL (may be transfused to maintain or exceed this level)
- Serum creatinine < 150 µmol/L
- Calculated creatinine clearance > 30 mL/min
- Total bilirubin < 1.5 times upper limit of normal
- 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 > grade 1
- No total or partial bowel obstruction
- No uncontrolled hypercalcemia
- 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 ≥ 5 years
- No other serious and uncontrolled non-malignant disease
- 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Tumor response, in terms of objective response rates (complete response and partial response)
Safety Issue:
No
Principal Investigator
Frederique Maindrault-Goebel, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Hopital Saint Antoine
Authority:
Unspecified
Study ID:
CDR0000701454
NCT ID:
NCT01375816
Start Date:
May 2011
Completion Date:
Related Keywords:
- Colorectal Cancer
- adenocarcinoma of the colon
- recurrent colon cancer
- stage IV colon cancer
- adenocarcinoma of the rectum
- recurrent rectal cancer
- stage IV rectal cancer
- Colorectal Neoplasms
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