Bevacizumab in Treating Patients Who Have Undergone First-Line Therapy for Metastatic Colorectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00544700
Recruitment Status : Active, not recruiting
First Posted : October 16, 2007
Last Update Posted : February 12, 2018
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research

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 tumor cells by blocking blood flow to the tumor. It is not yet known whether giving bevacizumab as maintenance therapy is more effective than observation in treating patients with colorectal cancer.

PURPOSE: This randomized phase III trial is studying bevacizumab to see how well it works in treating patients who have undergone first-line therapy for metastatic colorectal cancer.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Biological: bevacizumab Other: no maintenance Phase 3

Detailed Description:



  • To demonstrate that time to progression (TTP) without further treatment is not inferior to TTP with maintenance therapy comprising bevacizumab in patients with metastatic colorectal cancer and stable or responding disease after completion of standard first-line chemotherapy/bevacizumab treatment.


  • To evaluate the safety of bevacizumab maintenance therapy in these patients.
  • To assess the long-term cost implications of prolonged treatment with bevacizumab.

OUTLINE: This is a multicenter study. Patients are stratified according to best response during first-line chemotherapy/bevacizumab treatment (complete response and partial response vs stable disease), duration of first-line treatment (16-20 weeks vs 21-24 weeks), type of chemotherapy used during first-line treatment (irinotecan and fluoropyrimidine vs oxaliplatin and fluoropyrimidine vs fluoropyrimidine monotherapy), disease burden (one organ with metastasis vs more than one organ with metastasis), and by participating center.

  • Arm I (bevacizumab maintenance therapy): Patients receive bevacizumab IV over 30 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
  • Arm II (no maintenance therapy): Patients receive no further treatment; they are monitored for disease progression.

After completion of study therapy or documentation of disease progression, patients are followed every 3 months for 1 year and then every 6 months for up to 5 years.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 265 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Bevacizumab Maintenance Versus no Maintenance After Stop of First-line Chemotherapy in Patients With Metastatic Colorectal Cancer. A Randomized Multicenter Phase III Non-inferiority Trial
Actual Study Start Date : October 5, 2007
Actual Primary Completion Date : January 21, 2013
Estimated Study Completion Date : January 30, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Bevacizumab

Arm Intervention/treatment
Active Comparator: Arm A: Bevacizumab monotherapy
Bevacizumab maintenance monotherapy
Biological: bevacizumab
7.5 mg/kg i.v. bevacizumab every 21 days until progression or unacceptable toxicity
Other Name: Avastin®

Arm B: No maintenance
No antitumor treatment until progression
Other: no maintenance
No treatment until progression

Primary Outcome Measures :
  1. Time to progression (TTP) [ Time Frame: From randomization until documented progressive disease or death due to tumor. ]
    TTP will be calculated from randomization until documented PD or death due to tumor.

Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: OS will be calculated from start of first-line treatment until death. Additionally, OS will be calculated from randomization until death. ]
    OS will be calculated from start of first-line treatment until death. Additionally, OS will be calculated from randomization until death.

  2. Progression-free survival (PFS) [ Time Frame: From start of first-line treatment until documented PD or death, whichever occurs first. ]
    PFS will be calculated from start of first-line treatment until documented PD or death, whichever occurs first. Additionally, PFS will be calculated from randomization until documented PD or death, whichever occurs first.

  3. Adverse events (AE) [ Time Frame: Predefined AEs and AEs ≥ grade 3 will be assessed according to NCI CTCAE v3.0. ]
    Predefined AEs and AEs ≥ grade 3 will be assessed according to NCI CTCAE v3.0.

  4. Long-term bevacizumab treatment costs [ Time Frame: Estimated for the time period between randomization and the end of the follow-up phase (lasting maximal 5 years). ]
    Costs of bevacizumab treatment, including additional treatments and/or hospitalisations related to bevacizumab, as well as other anticancer treatments and their related hospitalisations, will be estimated for the time period between randomization and the end of the follow-up phase (lasting maximal 5 years) from information collected on the CRFs during trial treatment and follow-up phase.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically or cytologically confirmed metastatic colorectal cancer
  • Received prior first-line chemotherapy with oral or intravenous fluoropyrimidine alone or in combination with irinotecan or oxaliplatin

    • Chemotherapy must have been given in combination with a standard dose of bevacizumab for 16-24 weeks as part of first-line treatment for metastatic colorectal cancer
  • Stable disease, partial response, or complete response after completion of first-line treatment as documented by abdominal and thoracic CT scan, MRI, or x-ray within the past 21 days
  • No clinical symptoms or history of CNS metastases

    • No imaging required in asymptomatic patients


  • WHO performance status 0-1
  • Serum creatinine < 2.0 mg/dL or 177 μmol/L
  • Proteinuria < 2+ by urine dipstick OR urine protein ≤ 1 g by 24-hour urine collection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 12 months after completion of study therapy
  • Must have basic health insurance with a Swiss health insurance company
  • Patients must be compliant and in geographic proximity to allow proper staging and follow-up
  • No medical reason that prohibits further bevacizumab treatment, including any of the following:

    • Uncontrolled hypertension (systolic blood pressure [BP] > 150 mm Hg and/or diastolic BP > 100 mm Hg) or clinically significant (i.e., active) cardiovascular disease
    • Serious non-healing wound, active peptic ulcer, or non-healing bone fracture
    • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
    • History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding
  • No serious underlying medical condition that, in the judgment of the investigator, could further impair the ability of the patient to participate in the trial (e.g., active autoimmune disease or uncontrolled diabetes)
  • No psychiatric disorder that would preclude patient understanding of study-related topics or giving informed consent


  • See Disease Characteristics
  • At least 4 weeks since prior bevacizumab
  • No prior anti-EGFR treatment (e.g., cetuximab) during first-line therapy
  • No anticipation of concurrent major surgery (e.g., resection) or ablation of metastases
  • No concurrent elective major surgery
  • No concurrent daily aspirin exceeding 325 mg/day or clopidogrel exceeding 75 mg/day

    • Lower doses of the drugs noted above, or non-steroidal anti-inflammatory drugs with activity on platelets and gastric mucosa, or dipyridamole are allowed if given at a stable dose for ≥ 2 weeks prior to study entry
  • No other concurrent experimental drugs or anticancer therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00544700

Kantonsspital Aarau
Aarau, Switzerland, CH-5000
Hirslanden Klinik Aarau
Aarau, Switzerland, CH-5001
Kantonsspital Baden
Baden, Switzerland, CH-5404
St. Claraspital AG
Basel, Switzerland, CH-4016
Basel, Switzerland, CH-4031
Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
Bellinzona, Switzerland, 6500
Inselspital, Bern
Bern, Switzerland, CH-3010
Spitalzentrum Biel
Biel, Switzerland, CH-2501
Kantonsspital Bruderholz
Bruderholz, Switzerland, CH-4101
Spital Buelach
Bulach, Switzerland, CH-8180
AndreasKlinik Cham Zug
Cham, Switzerland, CH-6330
Kantonsspital Graubuenden
Chur, Switzerland, CH-7000
Hopital Fribourgeois
Fribourg, Switzerland, 1708
Hopital Cantonal Universitaire de Geneve
Geneva, Switzerland, CH-1211
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
Kantonsspital Liestal
Liestal, Switzerland, CH-4410
Istituto Oncologico della Svizzera Italiana
Lugano, Switzerland, CH-6900
Kantonsspital Luzern
Luzerne, Switzerland, CH-6000
Onkologie Zentrum am Spital Maennedorf
Männedorf, Switzerland, 8708
Kantonsspital Olten
Olten, Switzerland, CH-4600
Hopital Regional de Sion-Herens-Conthey
Sion, Switzerland, CH -1951
Kantonsspital - St. Gallen
St. Gallen, Switzerland, CH-9007
Thun, Switzerland, 3600
Spital Uster
Uster, Switzerland, 8610
Kantonsspital Winterthur
Winterthur, Switzerland, CH-8400
Onkozentrum Klinik im Park
Zurich, Switzerland, 8038
Klinik Hirslanden
Zurich, Switzerland, CH-8008
Stadtspital Waid
Zurich, Switzerland, CH-8037
UniversitaetsSpital Zuerich
Zurich, Switzerland, CH-8091
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Study Chair: Dieter Koeberle, MD St. Claraspital Basel
Study Chair: Peter Moosmann, MD Kantonsspital Aarau

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Swiss Group for Clinical Cancer Research Identifier: NCT00544700     History of Changes
Other Study ID Numbers: SAKK 41/06
First Posted: October 16, 2007    Key Record Dates
Last Update Posted: February 12, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Swiss Group for Clinical Cancer Research:
stage IV colon cancer
stage IV rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents