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Bevacizumab and Combination Chemotherapy as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed By Surgery

Primary Purpose

Colorectal Cancer

Status

Completed

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

bevacizumab

capecitabine

fluorouracil

irinotecan hydrochloride

leucovorin calcium

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

C.H.U. de Brest
Centre Regional Francois Baclesse
Centre de Lutte Contre le Cancer Georges-Francois Leclerc
Centre Oscar Lambret
Polyclinique des Quatre Pavillons
Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
Centre Antoine Lacassagne
Institut Curie Hopital
Polyclinique Francheville
Institut Jean Godinot
Centre Eugene Marquis
Centre Rene Huguenin
Centre Alexis Vautrin
Institut Gustave Roussy

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

bevacizumab + FOLFIRI

bevacizumab + XELIRI

Arm Description

Outcomes

Primary Outcome Measures

Progression-free survival at 6 months

Secondary Outcome Measures

Percentage of objective responses

Percentage of stable disease responses

Duration of objective response and stable disease

Progression-free survival

Overall survival

Toxicities

Quality of life

Full Information

NCT ID

NCT00423696

First Posted

January 16, 2007

Last Updated

February 15, 2021

Sponsor

UNICANCER

1. Study Identification

Unique Protocol Identification Number

NCT00423696

Brief Title

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

2. Study Status

Record Verification Date

February 2021

Overall Recruitment Status

Completed

Study Start Date

March 23, 2006 (Actual)

Primary Completion Date

July 28, 2008 (Actual)

Study Completion Date

August 1, 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

UNICANCER

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Cancer

Keywords

stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

145 (Actual)

8. Arms, Groups, and Interventions

Arm Title

bevacizumab + FOLFIRI

Arm Type

Experimental

Arm Title

bevacizumab + XELIRI

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

bevacizumab

Intervention Type

Drug

Intervention Name(s)

capecitabine

Intervention Type

Drug

Intervention Name(s)

fluorouracil

Intervention Type

Drug

Intervention Name(s)

irinotecan hydrochloride

Intervention Type

Drug

Intervention Name(s)

leucovorin calcium

Primary Outcome Measure Information:

Title

Progression-free survival at 6 months

Secondary Outcome Measure Information:

Title

Percentage of objective responses

Title

Percentage of stable disease responses

Title

Duration of objective response and stable disease

Title

Progression-free survival

Title

Overall survival

Title

Toxicities

Title

Quality of life

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michel Ducreux, MD, PhD

Organizational Affiliation

Gustave Roussy, Cancer Campus, Grand Paris

Official's Role

Study Chair

Facility Information:

Facility Name

C.H.U. de Brest

City

Brest

ZIP/Postal Code

29200

Country

France

Facility Name

Centre Regional Francois Baclesse

City

Caen

ZIP/Postal Code

14076

Country

France

Facility Name

Centre de Lutte Contre le Cancer Georges-Francois Leclerc

City

Dijon

ZIP/Postal Code

21079

Country

France

Facility Name

Centre Oscar Lambret

City

Lille

ZIP/Postal Code

59020

Country

France

Facility Name

Polyclinique des Quatre Pavillons

City

Lormont

ZIP/Postal Code

33310

Country

France

Facility Name

Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes

City

Marseille

ZIP/Postal Code

13273

Country

France

Facility Name

Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle

City

Montpellier

ZIP/Postal Code

34298

Country

France

Facility Name

Centre Antoine Lacassagne

City

Nice

ZIP/Postal Code

06189

Country

France

Facility Name

Institut Curie Hopital

City

Paris

ZIP/Postal Code

75248

Country

France

Facility Name

Polyclinique Francheville

City

Perigueux

ZIP/Postal Code

24004

Country

France

Facility Name

Institut Jean Godinot

City

Reims

ZIP/Postal Code

51056

Country

France

Facility Name

Centre Eugene Marquis

City

Rennes

ZIP/Postal Code

35062

Country

France

Facility Name

Centre Rene Huguenin

City

Saint Cloud

ZIP/Postal Code

92210

Country

France

Facility Name

Centre Alexis Vautrin

City

Vandoeuvre-les-Nancy

ZIP/Postal Code

54511

Country

France

Facility Name

Institut Gustave Roussy

City

Villejuif

ZIP/Postal Code

F-94805

Country

France

12. IPD Sharing Statement

Citations:

PubMed Identifier

21825101

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.

Results Reference

result

PubMed Identifier

31462288

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.

Results Reference

derived

Learn more about this trial

Bevacizumab and Combination Chemotherapy as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed By Surgery

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