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Phase II Randomized Study of First-Line Therapy Comprising Bevacizumab and Irinotecan Hydrochloride, Leucovorin Calcium, and Fluorouracil (FOLFIRI) Versus Bevacizumab and Irinotecan Hydrochloride and Capecitabine (XELIRI) in Patients With Unresectable Metastatic Colorectal Cancer [ACCORD]


Phase 2
18 Years
75 Years
Open (Enrolling)
Both
Colorectal Cancer

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Trial Information

Phase II Randomized Study of First-Line Therapy Comprising Bevacizumab and Irinotecan Hydrochloride, Leucovorin Calcium, and Fluorouracil (FOLFIRI) Versus Bevacizumab and Irinotecan Hydrochloride and Capecitabine (XELIRI) in Patients With Unresectable Metastatic Colorectal Cancer [ACCORD]


OBJECTIVES:

Primary

- Compare the progression-free survival at 6 months in patients with unresectable
metastatic colorectal cancer treated with first-line therapy comprising bevacizumab and
irinotecan hydrochloride, leucovorin calcium, and fluorouracil (FOLFIRI) vs bevacizumab
and irinotecan hydrochloride and capecitabine (XELIRI).

Secondary

- Compare the toxicities of these regimens in these patients.

- Compare the objective response rate and duration of response in patients treated with
these regimens.

- Compare the tumor control in patients treated with these regimens.

- Compare the progression-free and overall survival of patients treated with these
regimens.

- Compare the quality of life of patients treated with these regimens.

OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified
according to participating center, WHO performance status (0 or 1 vs 2), age (< 65 years vs
≥ 65 years), and number of metastatic sites (1 vs ≥ 2). Patients are randomized to 1 of 2
treatment arms.

- Arm I: Patients receive bevacizumab IV over 30-90 minutes, irinotecan hydrochloride IV
over 90 minutes, and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV
continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for 12
courses in the absence of disease progression or unacceptable toxicity. Patients may
then continue to receive bevacizumab alone every 2 weeks in the absence of disease
progression.

- Arm II: Patients receive bevacizumab IV over 30-90 minutes and irinotecan hydrochloride
IV over 90 minutes on day 1 and oral capecitabine on days 1-14. Treatment repeats every
3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
Patients may then continue to receive bevacizumab alone every 3 weeks in the absence of
disease progression.

Quality of life is assessed periodically.

After completion of study therapy, patients are followed periodically.

PROJECTED ACCRUAL: A total of 144 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed colorectal cancer

- Unresectable metastatic disease

- Measurable disease

- No CNS metastases

PATIENT CHARACTERISTICS:

- WHO performance status 0-2

- Life expectancy > 3 months

- Absolute neutrophil count > 1,500/mm³

- Platelet count > 100,000/mm³

- Hemoglobin > 9 g/dL (transfusion allowed)

- INR < 1.5

- Alkaline phosphatase < 1.5 times upper limit of normal (ULN)

- Bilirubin < 1.5 times ULN

- AST and ALT < 2.5 times ULN (5 times ULN if liver metastases are present)

- Creatinine clearance > 30 mL/min

- Urine protein < 2+ OR ≤ 1 g/L by 24-hour urine collection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No contraindications to study therapy

- No gastrointestinal or duodenal ulcers

- No AIDS

- No serious illness, active infection, or other serious condition that would preclude
study therapy

- No coagulation problem

- No bleeding diathesis

- No sensitivity to Chinese hamster ovarian cells or other recombinant human antibodies

- No severe renal insufficiency

- No uncontrolled hypertension

- No active or severe cardiovascular conditions, including the following:

- Cerebrovascular accident

- Myocardial infarction within the past 6 months

- New York Heart Association class II-IV cardiac insufficiency

- Severe cardiac arrhythmia (even if treated)

- No primitive stenosis or symptomatic peritoneal carcinosis causing a risk of
intestinal subocclusion or occlusion

- No nonhealing wound or fracture

- No prior thromboembolic disease

- No other cancer within the past 2 years except for basal cell skin cancer or
carcinoma in situ of the uterine cervix

- No geographical, social, or psychological condition that would preclude study
participation

PRIOR CONCURRENT THERAPY:

- No prior chemotherapy for metastatic disease

- At least 6 months since prior adjuvant chemotherapy (fluorouracil with or without
oxaliplatin)

- No prior adjuvant chemotherapy comprising irinotecan hydrochloride with or
without bevacizumab

- At least 28 days since prior major surgery

- Prior radiotherapy allowed except to target lesions

- At least 10 days since prior anticoagulants

- No concurrent chronic acetylsalicylic acid (at doses > 325 mg/day)

- No other concurrent investigational therapy

- No other concurrent anticancer therapy

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival at 6 months

Safety Issue:

No

Principal Investigator

Michel Ducreux, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Gustave Roussy, Cancer Campus, Grand Paris

Authority:

United States: Federal Government

Study ID:

CDR0000523435

NCT ID:

NCT00423696

Start Date:

January 2006

Completion Date:

Related Keywords:

  • Colorectal Cancer
  • stage IV colon cancer
  • stage IV rectal cancer
  • recurrent colon cancer
  • recurrent rectal cancer
  • Colorectal Neoplasms

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