Clinical trial NCT00423696: Bevacizumab and Combination Chemotherapy as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed By Surgery
Official title: 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]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2007-01-18
Enrollment: 145
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with combination chemotherapy may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective when given together with bevacizumab in treating patients with colorectal cancer.

PURPOSE: This randomized phase II trial is studying bevacizumab to compare how well it works when given together with two different combination chemotherapy regimens as first-line therapy in treating patients with metastatic colorectal cancer that cannot be removed by surgery.

Detailed description: 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.

Eligibility 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

Primary outcomes:
measure: Progression-free survival at 6 months
Secondary outcomes:
measure: Percentage of objective responses
measure: Percentage of stable disease responses
measure: Duration of objective response and stable disease
measure: Progression-free survival
measure: Overall survival
measure: Toxicities
measure: Quality of life
Other outcomes:
Locations:
city: Brest
country: France
facility: C.H.U. de Brest
city: Caen
country: France
facility: Centre Regional Francois Baclesse
city: Dijon
country: France
facility: Centre de Lutte Contre le Cancer Georges-Francois Leclerc
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lormont
country: France
facility: Polyclinique des Quatre Pavillons
city: Marseille
country: France
facility: Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Institut Curie Hopital
city: Perigueux
country: France
facility: Polyclinique Francheville
city: Reims
country: France
facility: Institut Jean Godinot
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Saint Cloud
country: France
facility: Centre Rene Huguenin
city: Vandoeuvre-les-Nancy
country: France
facility: Centre Alexis Vautrin
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Gustave Roussy, Cancer Campus, Grand Paris
name: Michel Ducreux, MD, PhD
role: STUDY_CHAIR
References:
citation: Malka D, Boige V, Jacques N, Vimond N, Adenis A, Boucher E, Pierga JY, Conroy T, Chauffert B, Francois E, Guichard P, Galais MP, Cvitkovic F, Ducreux M, Farace F. Clinical value of circulating endothelial cell levels in metastatic colorectal cancer patients treated with first-line chemotherapy and bevacizumab. Ann Oncol. 2012 Apr;23(4):919-27. doi: 10.1093/annonc/mdr365. Epub 2011 Aug 8.
citation: Antoun S, Bayar MA, Dyevre V, Lanoy E, Smolenschi C, Ducreux M. No evidence for changes in skeletal muscle mass or weight during first-line chemotherapy for metastatic colorectal cancer. BMC Cancer. 2019 Aug 28;19(1):847. doi: 10.1186/s12885-019-6086-2.