A Study of Avastin (Bevacizumab) and Xeloda (Capecitabine) as Maintenance Treatment in Patients With Metastatic Colorectal Cancer

A Randomized, Multicenter Phase III Trial to Assess the Efficacy and Safety of Bevacizumab and Capecitabine as Maintenance Treatment, After Initial Combination Treatment With Capecitabine, Oxaliplatin and Bevacizumab in Patients With Metastatic Colorectal Adenocarcinoma

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00623805

Enrollment

123

Registered

2008-02-26

Start date

2008-03-31

Completion date

2012-05-31

Last updated

2014-08-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Colorectal Cancer

Brief summary

This 2 arm study assessed the efficacy and safety of maintenance treatment with Avastin (bevacizumab) + Xeloda (capecitabine), after initial treatment with Xeloda + oxaliplatin + Avastin, in patients with metastatic colorectal cancer. Patients were randomized into one of 2 groups to receive 1) Xeloda + oxaliplatin + Avastin until disease progression or 2) Xeloda + oxaliplatin + Avastin for 6 3-week cycles, followed by Xeloda + Avastin until disease progression. Xeloda was administered at a dose of 1000 mg/m\^2 orally twice a day on days 1-14 of each cycle, oxaliplatin at a dose of 130 mg/m\^2 intravenously (iv) on day 1 of each cycle, and Avastin at a dose of 7.5 mg/kg iv on day 1 of each cycle.

Interventions

DRUGBevacizumab

Bevacizumab was supplied as a solution in single-use vials.

DRUGCapecitabine

Capecitabine was supplied as film-coated tablets.

DRUGOxaliplatin

Oxaliplatin was supplied as a lyophilized powder in vials.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Adult patients, ≥ 18 years of age. * Histologically confirmed colon or rectal cancer, with unresectable metastatic disease. * At least 1 measurable lesion. * Outpatient, with Eastern Cooperative Oncology Group (ECOG) Performance Status = 0-1.

Exclusion criteria

* Previous treatment with Avastin. * Previous systemic treatment for advanced or metastatic disease. * clinically significant cardiovascular disease. * Daily chronic treatment with high doses of aspirin (\> 325 mg/day) or non-steroidal anti-inflammatory drugs.

Design outcomes

Primary

Measure	Time frame	Description
Progression-free Survival	Baseline to the end of the study (up to 4 years, 2 months)	Progression-free survival was defined as the time from the first administration of study drug to the first documented disease progression or death, whichever occurs first. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the unequivocal progression of existing non-target lesions. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions at Baseline. Target lesions should be selected on the basis of their size (lesions with the longest diameter) and their suitability for accurate repeated measurements (either by imaging techniques or clinically). A sum of the longest diameter for all target lesions will be calculated and reported as the Baseline sum longest diameter.

Secondary

Measure	Time frame	Description
Overall Survival	Baseline to the end of the study (up to 4 years, 2 months)	Overall survival was defined as the time from the first administration of study drug to death.
Percentage of Participants With a Complete Response or a Partial Response	Baseline to the end of the study (up to 4 years, 2 months)	A complete response was defined as the disappearance of all target lesions. A partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the Baseline sum longest diameter. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions at Baseline. All other lesions (or sites of disease) should be identified as non-target lesions. Target lesions should be selected on the basis of their size (lesions with the longest diameter) and their suitability for accurate repeated measurements (either by imaging techniques or clinically). A sum of the longest diameter for all target lesions will be calculated and reported as the Baseline sum longest diameter.
Percentage of Participants With a R0 Resection	Baseline to the end of the study (up to 4 years, 2 months)	An R0 resection indicates a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed.
Duration of Response	Baseline to the end of the study (up to 4 years, 2 months)	Duration of response was defined as the time from the first complete response or partial response until disease progression or death. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the unequivocal progression of existing non-target lesions. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions at Baseline. Target lesions should be selected on the basis of their size (lesions with the longest diameter) and their suitability for accurate repeated measurements (either by imaging techniques or clinically). A sum of the longest diameter for all target lesions will be calculated and reported as the Baseline sum longest diameter.
Percentage of Participants With Metastatic Lesions Previously Considered Inoperable Who Became Operable and Underwent Surgery	Baseline to the end of the study (up to 4 years, 2 months)	—
Time Until a Complete Response or a Partial Response	Baseline to Month 13	Time until a complete response or a partial response was defined as the time from the first administration of study drug until the first complete response or partial response.

Countries

Turkey (Türkiye)

Participant flow

Participants by arm

Arm	Count
Bevacizumab+Capecitabine+Oxaliplatin Participants received bevacizumab 7.5 mg/kg intravenously (IV) on Day 1 of each 3-week cycle + oxaliplatin 130 mg/m\^2 IV on Day 1 of each 3-week cycle + capecitabine 1000 mg/m\^2 orally twice a day on Days 1-14 of each 3-week cycle until disease progression.	62
Bevacizumab(B)+Capecitabine(C)+Oxaliplatin Followed by B+C Participants received bevacizumab 7.5 mg/kg intravenously (IV) on Day 1 of each 3-week cycle + oxaliplatin 130 mg/m\^2 IV on Day 1 of each 3-week cycle + capecitabine 1000 mg/m\^2 orally twice a day on Days 1-14 of each 3-week cycle for 6 cycles followed by bevacizumab 7.5 mg/kg intravenously (IV) on Day 1 of each 3-week cycle + capecitabine 1000 mg/m\^2 orally twice a day on Days 1-14 of each 3-week cycle until disease progression.	61
Total	123

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	9	6
Overall Study	Death	2	0
Overall Study	Lack of Efficacy	3	7
Overall Study	Lost to Follow-up	2	2
Overall Study	Protocol Violation	1	1
Overall Study	Reason not Specified	3	6

Baseline characteristics

Characteristic	Bevacizumab+Capecitabine+Oxaliplatin	Bevacizumab(B)+Capecitabine(C)+Oxaliplatin Followed by B+C	Total
Age, Continuous	56.9 years STANDARD_DEVIATION 11.2	57.6 years STANDARD_DEVIATION 11.3	57.2 years STANDARD_DEVIATION 11.2
Sex: Female, Male Female	23 Participants	23 Participants	46 Participants
Sex: Female, Male Male	39 Participants	38 Participants	77 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	62 / 62	61 / 61
serious Total, serious adverse events	12 / 62	21 / 61

Outcome results

Primary

Progression-free Survival

Progression-free survival was defined as the time from the first administration of study drug to the first documented disease progression or death, whichever occurs first. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the unequivocal progression of existing non-target lesions. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions at Baseline. Target lesions should be selected on the basis of their size (lesions with the longest diameter) and their suitability for accurate repeated measurements (either by imaging techniques or clinically). A sum of the longest diameter for all target lesions will be calculated and reported as the Baseline sum longest diameter.