A Trial of Paclitaxel and Bevacizumab vs. Gemcitabine, Paclitaxel, and Bevacizumab in Advanced Breast Cancer

Study Overview
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Brief Summary
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This study will compare the cancer response to both treatments for locally advanced or metastatic breast cancer

Official Title
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A Randomized Phase II Trial of Paclitaxel and Bevacizumab Versus Gemcitabine, Paclitaxel, and Bevacizumab as First Line Treatment for Locally Advanced or Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: gemcitabine
* Drug: paclitaxel
* Drug: bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females diagnosed with breast cancer and the cancer has spread to distant areas of the breast or organs. Must be able to measure the disease by specific medical parameters May have received breast cancer treatment in the early stage of the disease May be restricted in physically strenuous activity but able to carry out light work. Must have adequate organ function as seen in blood test results. Exclusion Criteria: Cancer that has spread to the brain. Unstable heart problems Unstable high blood pressure. Breast cancer treatment after the disease has considered to spread to other areas or organs. Unable to agree with the requirements of the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: paclitaxel plus bevacizumab (PB)<br>paclitaxel 90 milligrams per meter squared (mg/m2) administered intravenously (IV) on days 1, 8, 15 every 28 days followed by bevacizumab 10 milligrams per kilogram (mg/kg) administered IV on days 1 and 15 every 28 days | Drug: paclitaxel<br>* 90 mg/m2, IV, day 1, day 8 and day 15 every 28 days until complete response, disease progression or unacceptable toxicity<br>* Other names: Taxol;Drug: bevacizumab<br>* 10 mg/kg, IV, day 1 and day 15 every 28 days until complete response, disease progression or unacceptable toxicity<br>* Other names: Avastin;|
| Experimental: paclitaxel plus bevacizumab plus gemcitabine (PB+G)<br>paclitaxel 90 milligrams per meter squared (mg/m2) administered intravenously (IV) on days 1, 8, 15 every 28 days followed by gemcitabine 1500 mg/m2 IV on days 1 and 15 every 28 days followed by bevacizumab 10 milligrams per kilogram (mg/kg) administered IV on days 1 and 15 every 28 days | Drug: gemcitabine<br>* 1500 mg/m2, IV day 1 and day 15 every 28 days until complete response, disease progression or unacceptable toxicity<br>* Other names: Gemzar;Drug: paclitaxel<br>* 90 mg/m2, IV, day 1, day 8 and day 15 every 28 days until complete response, disease progression or unacceptable toxicity<br>* Other names: Taxol;Drug: bevacizumab<br>* 10 mg/kg, IV, day 1 and day 15 every 28 days until complete response, disease progression or unacceptable toxicity<br>* Other names: Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Response defined per Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes that do not meet above criteria. ORR was defined as the proportion of participants who achieved a best response of either CR or PR. ORR=number of participants with CR or PR/number of participants qualified for tumor response analysis (per-protocol population). | baseline & every 2 cycles (approximately 8 weeks) of treatment to measured progressive disease (PD) & post-therapy until PD or other therapy initiated (up to 35 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | PFS was measured from date of randomization to first date of disease progression or death from any cause. For participants not known to have died or had disease progression as of data-inclusion cut-off date, PFS duration was censored at date of last study visit prior to data-inclusion cut-off date. | baseline to measured progressive disease or death up to 35 months (tumor assessments were performed every 2 cycles during study therapy; every 2 months during post-therapy until disease progression or new anticancer treatment initiated) | 
| Overall Survival | Overall survival was measured from date of randomization to date of death from any cause. For participants not known to have died as of data-inclusion cut-off date, overall survival duration was censored at date of last study visit prior to the data cut-off date. | baseline to death from any cause (up to 35 months) | 
| Total Functional Assessment of Cancer Therapy -Breast (FACT-B): Change From Baseline to End of Therapy | FACT-B measures the following domains of health-related quality of life (HR-QL): physical well-being (PWB), social/family well-being (SFWB), emotional well-being (EWB), functional well-being (FWB), & additional concerns of breast cancer (BCS). Total FACT-B scores range from 0-144, with higher scores representing better HR-QOL. Minimally important differences estimates obtained for FACT-B is 7-8 points. FACT-B was assessed at baseline (prior to start of Cycle 1 [Day 1]), prior to start of each subsequent cycle (approximately every 4 weeks) during therapy, through 30-day post therapy follow-up. | Baseline through 30 days post therapy follow-up (up to 35 months) | 
| Physical Well Being (PWB) Subscale: Change From Baseline to End of Therapy | The PWB subscale of FACT-B measures physical well-being. Total PWB scores range from 0 to 28, with higher scores representing better HR-QOL. FACT-B was assessed at baseline (prior to start of Cycle 1 [Day 1]), then prior to start of each subsequent cycle (approximately every 4 weeks) during therapy, through 30-day post therapy follow-up. | Baseline through 30 days post therapy follow-up (up to 35 months) | 
| Social/Family Well Being (SFWB) Subscale: Change From Baseline to End of Therapy | The SFWB subscale of FACT-B measures social/family well-being. Total SFWB scores range from 0 to 28, with higher scores representing better HR-QOL. FACT-B was assessed at baseline (prior to start of Cycle 1 [Day 1]), then prior to start of each subsequent cycle (approximately every 4 weeks) during therapy, through 30-day post therapy follow-up. | Baseline through 30 days post therapy follow-up (up to 35 months) | 
| Emotional Well Being (EWB) Subscale: Change From Baseline to End of Therapy | The EWB subscale of FACT-B measures emotional well-being. Total EWB scores range from 0 to 24, with higher scores representing better HR-QOL. FACT-B was assessed at baseline (prior to start of Cycle 1 [Day 1]), then prior to start of each subsequent cycle (approximately every 4 weeks) during therapy, through 30-day post therapy follow-up. | Baseline through 30 days post therapy follow-up (up to 35 months) | 
| Functional Well Being (FWB) Subscale: Change From Baseline to End of Therapy | The FWB subscale of FACT-B measures functional well-being. Total FWB scores range from 0 to 28, with higher scores representing better HR-QOL. FACT-B was assessed at baseline (prior to start of Cycle 1 [Day 1]), then prior to start of each subsequent cycle (approximately every 4 weeks) during therapy, through 30-day post therapy follow-up. | Baseline through 30 days post therapy follow-up (up to 35 months) | 
| Breast Cancer Subscale (BCS): Change From Baseline to End of Therapy | The BCS subscale of FACT-B measures additional concerns of breast cancer . Total BCS scores range from 0 to 36, with higher scores representing better HR-QOL. Minimally important differences estimates obtained for BCS is 2-3 points. FACT-B was assessed at baseline (prior to start of Cycle 1 [Day 1]), then prior to start of each subsequent cycle (approximately every 4 weeks) during therapy, through 30-day post therapy follow-up. | Baseline through 30 days post therapy follow-up (up to 35 months) | 
| Trial Outcome Index-Breast (TOI-B): Change From Baseline to End of Therapy | The TOI-B represents the total of the subscales PWB,FWB, and BCS. Total TOI-B scores range from 0 to 92, with higher scores representing better HR-QOL. Minimally important differences estimates obtained for TOI is 5-6 points. FACT-B was assessed at baseline (prior to start of Cycle 1 [Day 1]), then prior to start of each subsequent cycle (approximately every 4 weeks) during therapy, through 30-day post therapy follow-up. | Baseline through 30 days post therapy follow-up (up to 35 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Cancer of Breast, Cancer of the breast, Breast Neoplasms