A Study of Bevacizumab in Combination With Gemcitabine and Carboplatin in Participants With Triple Negative Metastatic Breast Cancer

Study Overview
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Brief Summary
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This multicenter study will assess the efficacy and safety of bevacizumab in combination with gemcitabine and cisplatin as first line treatment in participants with triple negative metastatic breast cancer. Participants will receive bevacizumab at a dose of 15 mg/kg intravenously (iv) every 3 weeks, plus gemcitabine (1000 mg/m2 iv) and carboplatin (iv to an area under curve [AUC]=2) on Days 1 and 8 of each 3-week cycle. Anticipated time on study treatment is until disease progression.

Official Title
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A Multi Centre, Pilot Phase II Trial Assessing the Efficacy and Safety of Bevacizumab + Gemcitabine + Carboplatin as First Line Treatment for Patients Diagnosed With Triple Negative Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: Carboplatin
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female participants, >/= 18 years of age Metastatic breast cancer Estrogen receptor-, progesterone- and human epidermal growth factor receptor 2 (HER2)-negative disease Treatment-naïve for metastatic breast cancer Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Adequate hematological, renal and liver function Patients should have received Anthracyclines and Taxanes in the adjuvant setting Women of childbearing potential must agree to use adequate contraception (per institutional standard of care) during treatment and until 6 months after the last administration of investigational products Exclusion Criteria: Prior first line treatment for metastatic breast cancer Central nervous system (CNS) metastasis Uncontrolled hypertension (> 170/95 mmHg) Evidence of bleeding diathesis, coagulopathy or hemorrhage at baseline Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer. Prior therapy with gemcitabine or carboplatin in the metastatic setting. Participants having received gemcitabine or carboplatin as part of adjuvant therapy are eligible, if recurrence was first documented >6 months after the last exposure to the drug(s) Requirement of chronic use of immunosuppressive agents HIV, hepatitis B or hepatitis C infection

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Overall Participants<br>Participants received a combination therapy of bevacizumab with gemcitabine plus carboplatin. | Drug: Bevacizumab<br>* 15 mg/kg iv every 3 weeks<br>* Other names: Avastin;Drug: Carboplatin<br>* to an AUC = 2, on days 1 and 8 of each 3-week cycle<br>Drug: Gemcitabine<br>* 1000 mg/m2 iv on days 1 and 8 of each 3-week cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | Progression free survival (PFS) was calculated in days from the date of registration until the earliest date of documented disease progression or death. The median PFS time with 95% confidence interval (CI) was estimated using Kaplan Meier method. The progression-free survival was assessed utilizing computer tomography (CT)/ magnetic resonance imaging (MRI)/bone scans and X-ray and Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1. Progression of disease is defined as at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. | From the date of registration until the disease progression or death (up to 1541 days). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving an Overall Response | The overall response rate (ORR) was defined as complete response (CR) + partial response (PR). ORR was summarized using number and percentage along with two-sided 95% Pearson-Clopper CI. The overall response rate was assessed utilizing the RECIST v. 1.1. CR: disappearance of all target and non-target lesions (TLs) and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (<) 10 millimeter (mm). PR: at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters. | From the date of registration until the disease progression or death (up to 1541 days) | 
| Percentage of Participants Achieving a Clinical Benefit Response (CBR) | Clinical benefit response was defined as a complete response (CR), partial response (PR) or stable disease (SD). CBR was assessed using Recist v.1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. | From the date of registration until the disease progression or death (up to 1541 days) | 
| Time to Progression (TTP) | Duration of time to progression (TTP) was estimated using the Kaplan-Meier method. The time to progression was calculated in days from the date of registration until the earliest date of documented disease progression. | From the date of registration until the disease progression (up to 1541 days). | 
| Overall Survival (OS) | Overall survival was measured from the date of the first study drug dose to the date of death from any cause. The median overall survival time with 95%CI was estimated using Kaplan-Meier method. | From the date of registration until the disease progression or death (up to 1541 days) | 
| Number of Participants With an Adverse Event (AE) | An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. | Up to 28 days after termination of study treatment (approximately 1569 days) | 
| Change From Baseline to Cycle 6 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30) | The EORTC QLQ-C30 (version 3.0) questionnaire incorporates 9 multi scale items: 5 functional scales (physical, role, cognitive, emotional and social); 3 symptom scales (fatigue, pain and nausea & vomiting); and a global health and quality-of-life scale. It contains 30 questions. The score for each item and the overall score ranges from 0 to 100. A high overall scale and subscale scores represent improved health status. However, in case of symptoms, higher scores suggest increased perception of these symptoms. | Baseline, cycle 6 | 
| Change From Baseline in Systolic Blood Pressure (SBP) | Change from baseline in SBP was analyzed by overall response (CR+PR, SD+PD). | Baseline, Cycle 6, 12 of treatment | 
| Change From Baseline in Diastolic Blood Pressure (DBP) | Change from baseline in DBP was analyzed by overall response (CR+PR, SD+PD). | Baseline, Cycle 6, 12 of treatment |