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.
OBJECTIVES: Primary * 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. Secondary * 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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
265
7.5 mg/kg i.v. bevacizumab every 21 days until progression or unacceptable toxicity
No treatment until progression
Kantonsspital Aarau
Aarau, Switzerland
Hirslanden Klinik Aarau
Aarau, Switzerland
Kantonsspital Baden
Baden, Switzerland
St. Claraspital AG
Basel, Switzerland
Universitaetsspital-Basel
Basel, Switzerland
Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
Bellinzona, Switzerland
Inselspital, Bern
Bern, Switzerland
Spitalzentrum Biel
Biel, Switzerland
Kantonsspital Bruderholz
Bruderholz, Switzerland
Spital Buelach
Bülach, Switzerland
...and 19 more locations
Time to progression (TTP)
TTP will be calculated from randomization until documented PD or death due to tumor.
Time frame: From randomization until documented progressive disease or death due to tumor.
Overall survival (OS)
OS will be calculated from start of first-line treatment until death. Additionally, OS will be calculated from randomization until death.
Time frame: OS will be calculated from start of first-line treatment until death. Additionally, OS will be calculated from randomization until death.
Progression-free survival (PFS)
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.
Time frame: From start of first-line treatment until documented PD or death, whichever occurs first.
Adverse events (AE)
Predefined AEs and AEs ≥ grade 3 will be assessed according to NCI CTCAE v3.0.
Time frame: Predefined AEs and AEs ≥ grade 3 will be assessed according to NCI CTCAE v3.0.
Long-term bevacizumab treatment costs
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.
Time frame: Estimated for the time period between randomization and the end of the follow-up phase (lasting maximal 5 years).
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