2-arm Trial of Paclitaxel Plus Bevacizumab vs. Capecitabine Plus Bevacizumab

Phase 3

Completed

Conditions: Metastatic Breast Cancer

Registration Number: NCT00600340

Lead Sponsor: Central European Cooperative Oncology Group

Brief Summary: First-line treatment of patients with locally recurrent or metastatic, HER2-negative breast cancer who have not received prior chemotherapy for locally recurrent or metastatic disease.

Detailed Description: Arm A:

Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks

Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks

Arm B:

Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks

Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks

In both arms treatment will be given until first disease progression (PD), unacceptable toxicity or withdrawal of patient consent.

For patients who stop chemotherapy for any reason before PD (e.g. toxicity) the other treatment should be given as monotherapy until PD.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 564

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Overall Survival (PP Population)	Time from the date of randomization to the date of death or date last known to be alive, assessed up to approximately 6 years	Overall survival (OS) defined as time from randomization to date of death from any cause. Patients without recorded death were censored at the date the patient was last known to be alive. OS was analyzed at two looks, one interim look and the final analysis. Due to group sequential testing, the overall significance level alpha = 0.025 was spent on both looks according to Lan-DeMets spending method with O'Brien-Fleming-type boundaries. Alpha spent at Interim after 47% of information was 0.0010. Alpha spent at final analysis after 99% of information was 0.0250.
Overall Survival (ITT Population)	Time from the date of randomization to the date of death or date last known to be alive, assessed up to approximately 6 years	Overall survival (OS) defined as time from randomization to date of death from any cause. Patients without recorded death were censored at the date the patient was last known to be alive. OS was analyzed at two looks, one interim look and the final analysis. Due to group sequential testing, the overall significance level alpha = 0.025 was spent on both looks according to Lan-DeMets spending method with O'Brien-Fleming-type boundaries. Alpha spent at Interim after 50% of information was 0.0014. Alpha spent at final analysis after 99% of information was 0.0250.

Secondary Outcome Measures

Name	Time	Method
Observation Time (ITT Population)	Up to approximately 6 years	Median observation time estimated with reverse Kaplan-Meier methods. Observation time (in months) is defined as time from randomization to the day the patient was last confirmed to be alive. In case of patient deaths the time was censored at the day of death.
Best Overall Response (ITT Population)	Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.	The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase
Best Overall Response (PP Population)	Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.	The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase
Unconfirmed Best Overall Response (ITT Population)	Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.	The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase. Complete and partial response in this summary did not require a confirmation by a second tumor assessment.
Unconfirmed Best Overall Response (PP Population)	Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.	The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase. Complete and partial response in this summary did not require a confirmation by a second tumor assessment.
Objective Response Rate and Disease Control Rate (ITT Population)	Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.	Objective response rate (ORR) is defined as the proportion of patients with complete response or partial response. Disease control rate (DCR) is defined as the proportion of patients with complete response, partial response and stable disease. The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase
Progression Free Survival (ITT Population)	Time from the date of randomization to disease progression, death or censoring (whichever occurred first), assessed up to approximately 5 years.	Progression Free Survival (PFS) is defined as time from randomization to date of documented progression or date of death due to any cause, whichever occurred first. Patients without recorded progression or death were censored at the last date they were known to have not progressed. Patients who were randomized and had no post-baseline tumor assessment were censored on the day of randomization. Median PFS, associated stratified Hazard Ratio (HR).
Progression Free Survival (PP Population)	Time from the date of randomization to disease progression, death or censoring (whichever occurred first), assessed up to approximately 5 years.	Progression Free Survival (PFS) is defined as time from randomization to date of documented progression or date of death due to any cause, whichever occurred first. Patients without recorded progression or death were censored at the last date they were known to have not progressed. Patients who were randomized and had no post-baseline tumor assessment were censored on the day of randomization. Median PFS, associated stratified Hazard Ratio (HR).
Time to Treatment Failure (ITT Population)	From first drug intake to progression, death or withdrawal from study treatment or study closure (whichever occurred first), assessed up to approximately 4.5 years	Time to treatment failure (TTF) was defined as time from first drug intake to progression, death or withdrawal from study treatment, whichever occurred first. Patients without an event were censored at the date of the last tumor assessment or last treatment administration, whichever occurred last. Median TTF, associated stratified Hazard Ratio (HR).
Objective Response Rate and Disease Control Rate (PP Population)	Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.	Objective response rate (ORR) is defined as the proportion of patients with complete response or partial response. Disease control rate (DCR) is defined as the proportion of patients with complete response, partial response and stable disease. The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase
Unconfirmed Objective Response Rate and Disease Control Rate (ITT Population)	Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.	Objective response rate (ORR) is defined as the proportion of patients with complete response or partial response. Disease control rate (DCR) is defined as the proportion of patients with complete response, partial response and stable disease. The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase. Complete and partial response in this summary did not require a confirmation by a second tumor assessment.
Time to Treatment Failure (PP Population)	From first drug intake to progression, death or withdrawal from study treatment or study closure (whichever occurred first), assessed up to approximately 4.5 years	Time to treatment failure (TTF) was defined as time from first drug intake to progression, death or withdrawal from study treatment, whichever occurred first. Patients without an event were censored at the date of the last tumor assessment or last treatment administration, whichever occurred last. Median TTF, associated stratified Hazard Ratio (HR).
Time to Response (ITT Population)	Time from randomization until occurrence of response, assessed up 1.7 years	Time to response (TR) was defined as time from randomization until occurrence of response (complete response (CR) or partial response (PR)) according to RECIST criteria. Patients without response were censored after the longest time to response observed in any patient. Median TR, associated stratified Hazard Ratio (HR). Since the median TR was not observed, the number of subjects with a response at given timepoints were reported.
Unconfirmed Objective Response Rate and Disease Control Rate (PP Population)	Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.	Objective response rate (ORR) is defined as the proportion of patients with complete response or partial response. Disease control rate (DCR) is defined as the proportion of patients with complete response, partial response and stable disease. The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase. Complete and partial response in this summary did not require a confirmation by a second tumor assessment
Time to Response (PP Population)	Time from randomization until occurrence of response, assessed up 1.7 years	Time to response (TR) was defined as time from randomization until occurrence of response (complete response (CR) or partial response (PR)) according to RECIST criteria. Patients without response were censored after the longest time to response observed in any patient. Median TR, associated stratified Hazard Ratio (HR). Since the median TR was not observed, the number of subjects with a response at given timepoints were reported.
Duration of Response (ITT Population)	Time from first occurrence of CR or PR until disease progression, death or study closure, whichever occurred first, assessed up to 3.4 years after occurrence of response.	Duration of response (DR) was defined as time from date of first occurrence of any response (complete response (CR) or partial response (PR)) until the occurrence of progression of disease or death. Patients with response who neither progressed nor died were censored at the date of their last tumor assessment. Median DR, associated stratified Hazard Ratio (HR).
Duration of Response (PP Population)	Time from first occurrence of CR or PR until disease progression, death or study closure, whichever occurred first, assessed up to 3.4 years after occurrence of response.	Duration of response (DR) was defined as time from date of first occurrence of any response (complete response (CR) or partial response (PR)) until the occurrence of progression of disease or death. Patients with response who neither progressed nor died were censored at the date of their last tumor assessment. Median DR, associated stratified Hazard Ratio (HR).

Trial Locations

Locations (55): LKH Leoben
🇦🇹
Leoben, Austria
Hospital Barmherzige Schwestern
🇦🇹
Linz, Austria
AKH Linz, Dep. of Oncology
🇦🇹
Linz, Austria
Hospital Elisabethinen Linz
🇦🇹
Linz, Austria
Univ. Klinik, Medicine III
🇦🇹
Salzburg, Austria
2. Med. Abteilung - LKH-Steyr
🇦🇹
Steyr, Austria
General Hospital, Medical University of Vienna
🇦🇹
Vienna, Austria
Hospital Hietzing
🇦🇹
Vienna, Austria
Institute of Oncology Sarajevo
🇧🇦
Sarajevo, Bosnia and Herzegovina
Cancer Center Plovdiv
🇧🇬
Plovdiv, Bulgaria
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LKH Leoben
🇦🇹Leoben, Austria