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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00544700
• Other study ID #: SAKK 41/06
• Secondary ID: SWS-SAKK-41/06EU
• Status: Terminated
• Phase: Phase 3
• Start date: November 26, 2007
• Est. completion date: December 12, 2019

Study information

• Verified date: February 2020
• Source: Swiss Group for Clinical Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 265
• Est. completion date: December 12, 2019
• Est. primary completion date: January 21, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

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

Other:
• no maintenance
No treatment until progression

Locations

Country	Name	City	State
Switzerland	Hirslanden Klinik Aarau	Aarau
Switzerland	Kantonsspital 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	Bulach
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	Hopital Regional de Sion-Herens-Conthey	Sion
Switzerland	Kantonsspital - St. Gallen	St. Gallen
Switzerland	Regionalspital	Thun
Switzerland	Spital Uster	Uster
Switzerland	Kantonsspital Winterthur	Winterthur
Switzerland	Klinik Hirslanden	Zurich
Switzerland	Onkozentrum Klinik im Park	Zurich
Switzerland	Stadtspital Waid	Zurich
Switzerland	UniversitaetsSpital Zuerich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
Swiss Group for Clinical Cancer Research

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to progression (TTP)	TTP will be calculated from randomization until documented PD or death due to tumor.	From randomization until documented progressive disease or death due to tumor.
Secondary	Overall survival (OS)	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.
Secondary	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.	From start of first-line treatment until documented PD or death, whichever occurs first.
Secondary	Adverse events (AE)	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.
Secondary	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.	Estimated for the time period between randomization and the end of the follow-up phase (lasting maximal 5 years).