Carboplatin, Abraxane, Avastin as Neoadjuvant Therapy for Her2-Negative Breast Cancer

Study Overview
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Brief Summary
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In the MDACC/BrUOG neoadjuvant trial with weekly paclitaxel followed by Fluorouracil Plus Doxorubicin and Cyclophosphamide (FAC), the pathologic complete response (pCR) rate in HER2(-) patients was 20%. The investigators' goal is to develop an induction chemotherapy regimen that will have a pCR rate above 30% in patients with HER2(-) disease. Based on a 1-sided 95% confidence interval using normal approximation with an expected pCR rate of at least 35%, approximately 28 patients are required for each cohort. With an assumed pCR rate of at least 35%, the investigators will have approximately 70% statistical power to conclude, with 90% certainty, that the pCR rate with the novel regimen exceeds 20%. The study will accrue approximately 60 patients in two cohorts with an inevaluable rate that does not exceed 10%.

Detailed Description
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See above brief summary

Official Title
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Q3week Carboplatin With Weekly Abraxaneä And Avastin + Subsequent Dose-Dense Ac With Avastin As Neoadjuvant Therapy In Resectable And Unresectable (Stage Iia-Iiib) Her2-Negative Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Abraxane
* Drug: Carboplatin
* Drug: Avastin


Participation Criteria
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Eligibility Criteria
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Eligibility criteria Inclusion criteria: Histologically documented adenocarcinoma of the breast ANC > 1000 cells Female; age > 18 Zubrod PS 0-1 Platelets > 100,000 Stage IIA-IIIB disease Total bilirubin < 1.5 ULN No evidence of any metastatic disease Serum Creatinine < 1.5 gm/dl No prior systemic therapy for breast cancer or Creat Cl > 30 ml/min Not pregnant or lactating Serum ALT < 2.0 ULN ER, PR and HER2 status required LVEF (MUGA/echo WNL) No baseline > 2 neuropathy Urine protein: creat ratio < 1.0 HER2-negative - either IHC 0-1+ or FISH ratio < 2.0 Hemoglobin > 9 gm/dl (FISH testing is required for all HER2 2-3+ tumors by IHC) Exclusion criteria: No Histologically documented adenocarcinoma of the breast No-ANC > 1000 cells Female; age < 18 Zubrod PS > 0-1 Platelets < 100,000 Stage IV disease Total bilirubin > 1.5 ULN metastatic disease Serum Creatinine > 1.5 gm/dl prior systemic therapy for breast cancer or Creat Cl > 30 ml/min pregnant or lactating Serum ALT > 2.0 ULN baseline > 2 neuropathy Urine protein: creat ratio >1.0 HER2-positive Hemoglobin < 9 gm/dl

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Avastin 10 mg/kg IV over 90 minutes day -14 Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 Avastin 10 mg/kg IV over 30-60 minutes cycles 1-3 (omit dose with cycle 4) Doxorubicin 60 mg/m2* and Cyclophosphamide 600 mg/m2 IV q2weeks x 4 cycles Definitive surgery Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 34 weeks | Drug: Abraxane<br>* Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks<br>* Other names: Paclitaxel Protein-Bound;Drug: Carboplatin<br>* Carboplatin at AUC 6 over 30 min IV weeks 1,4,7, and 10<br>* Other names: Paraplatin;Drug: Avastin<br>* Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 (in Cohort 2, omit dose of Avastin on week 10)<br>* Other names: Bevacizumab;|
| Experimental: Cohort 2<br>Abraxane 100 mg/m2 IV over 30 minutes days -14 and -7 Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7 Definitive surgery Avastin 10 mg/kg IV over 30-60 minutes and Doxorubicin 60 mg/m2* and Cyclophosphamide 600 mg/m2 IV q2weeks x 4 cycles followed by Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 34 weeks OR Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 42 weeks | Drug: Abraxane<br>* Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks<br>* Other names: Paclitaxel Protein-Bound;Drug: Carboplatin<br>* Carboplatin at AUC 6 over 30 min IV weeks 1,4,7, and 10<br>* Other names: Paraplatin;Drug: Avastin<br>* Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 (in Cohort 2, omit dose of Avastin on week 10)<br>* Other names: Bevacizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological Complete Response Rates at Surgery |  | at surgery approximately 5 months after initial treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Measure of safety and tolerability according to CTCAE version 3.0 | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer