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

NCT ID: NCT00544700

Last Updated: 2020-02-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 265 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-26
• Study Completion Date: 2019-12-12

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.

Detailed Description

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.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: Bevacizumab monotherapy

Bevacizumab maintenance monotherapy

Group Type: ACTIVE_COMPARATOR

bevacizumab

Intervention Type: BIOLOGICAL

7.5 mg/kg i.v. bevacizumab every 21 days until progression or unacceptable toxicity

Arm B: No maintenance

No antitumor treatment until progression

Group Type: OTHER

no maintenance

Intervention Type: OTHER

No treatment until progression

Interventions

bevacizumab

7.5 mg/kg i.v. bevacizumab every 21 days until progression or unacceptable toxicity

Intervention Type: BIOLOGICAL

no maintenance

No treatment until progression

Intervention Type: OTHER

Other Intervention Names

Avastin®

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

• 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

PRIOR CONCURRENT THERAPY:

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dieter Koeberle, MD

Role: STUDY_CHAIR

St. Claraspital Basel

Peter Moosmann, MD

Role: STUDY_CHAIR

Kantonsspital Aarau

Locations

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

AndreasKlinik Cham Zug

Cham, , Switzerland

Kantonsspital Graubuenden

Chur, , Switzerland

Hopital Fribourgeois

Fribourg, , Switzerland

Hopital Cantonal Universitaire de Geneve

Geneva, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Kantonsspital Liestal

Liestal, , Switzerland

Istituto Oncologico della Svizzera Italiana

Lugano, , Switzerland

Kantonsspital Luzern

Luzerne, , Switzerland

Onkologie Zentrum am Spital Maennedorf

Männedorf, , Switzerland

Kantonsspital Olten

Olten, , Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

Hopital Regional de Sion-Herens-Conthey

Sion, , Switzerland

Regionalspital

Thun, , Switzerland

Spital Uster

Uster, , Switzerland

Kantonsspital Winterthur

Winterthur, , Switzerland

Onkozentrum Klinik im Park

Zurich, , Switzerland

Klinik Hirslanden

Zurich, , Switzerland

Stadtspital Waid

Zurich, , Switzerland

UniversitaetsSpital Zuerich

Zurich, , Switzerland

Countries

Switzerland

References

Koeberle D, Betticher DC, von Moos R, Dietrich D, Brauchli P, Baertschi D, Matter K, Winterhalder R, Borner M, Anchisi S, Moosmann P, Kollar A, Saletti P, Roth A, Frueh M, Kueng M, Popescu RA, Schacher S, Hess V, Herrmann R. Bevacizumab continuation versus no continuation after first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a randomized phase III non-inferiority trial (SAKK 41/06). Ann Oncol. 2015 Apr;26(4):709-714. doi: 10.1093/annonc/mdv011. Epub 2015 Jan 20.

Reference Type: DERIVED

PMID: 25605741 (View on PubMed)

Other Identifiers

SWS-SAKK-41/06

Identifier Type: -

Identifier Source: secondary_id

EU-20762

Identifier Type: -

Identifier Source: secondary_id

CDR0000569866

Identifier Type: -

Identifier Source: secondary_id

SAKK 41/06

Identifier Type: -

Identifier Source: org_study_id