Neoadjuvant Carboplatin, Weekly Abraxane and Trastuzumab in HER2+ Breast Cancer

Study Overview
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Brief Summary
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Q3week carboplatin with weekly abraxane and trastuzumab as neoadjuvant therapy in resectable and unresectable HER2+ (stage IIa-IIIb) breast cancer

Detailed Description
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Our goal is to develop an induction chemotherapy regimen that will have a pCR rate above 50% in HER2+ patients without exposing patients to the toxicity of an anthracycline-based regimen. A minimum of 60 evaluable patients will be accrued to the study. We are assuming an observed pCR (or near pCR) rate of 70%. Assuming no more than 10% of patients will be inevaluable for the primary endpoint (pCR), we will have at least 54 evaluable patients. With this number, we will have 90% power, with a 1-sided alpha error of 0.05, to demonstrate a pCR rate exceeding 50% for our novel regimen.

Official Title
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BrUOG-BR-211B q3week Carboplatin With Weekly Abraxane and Trastuzumab As Neoadjuvant Therapy in Resectable and Unresectable HER2+ (Stage IIa-IIIb) Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Cohort 1 neo-adjuvant
* Drug: Cohort 2 neo-adjuvant
* Drug: Cohort 1 adjuvant
* Drug: Cohort 2 adjuvant


Participation Criteria
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Eligibility Criteria
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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 < or = ULN No evidence of metastatic disease Not pregnant or lactating No prior systemic therapy for this breast cancer Serum Creatinine < 1.5 mg/dl or Creat Cl > 30 ml/min Serum ALT < 2.5 x ULN ER, PR and HER2 status required LVEF (MUGA/echo)WNL No baseline > 2 neuropathy Hemoglobin > 9.0 gm/dl HER2+, defined by IHC 3+ or FISH ratio > 2.0

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: Neo-adjuvant cohort 1<br> | Drug: Cohort 1 neo-adjuvant<br>* Cohort 1 : Trastuzumab 6 mg/kg IV over 60 minutes day -14 Trastuzumab 2 mg/kg IV over 60 minutes weekly then Abraxane 100 mg/m2 IV over 30 minutes weekly x 18 weeks followed by Carboplatin at AUC 6 IV over 30 min weeks 1,4,7,10,13 and 16<br>* Other names: Abraxane (nab-paclitaxel), Herceptin (trastuzumab) and carboplatin;|
| Experimental: Neo-adjuvant cohort 2<br> | Drug: Cohort 2 neo-adjuvant<br>* Cohort 2 :Abraxane 100 mg/m2 IV over 30 minutes days -14 and -7 Trastuzumab 2 mg/kg IV over 60 minutes weekly (4 mg/kg week 1) then Abraxane 100 mg/m2 IV over 30 minutes weekly x 18 weeks followed by Carboplatin at AUC 6 IV over 30 min weeks 1,4,7,10,13 and 16<br>|
| Experimental: Adjuvant cohort 1<br> | Drug: Cohort 1 adjuvant<br>* Trastuzumab 8 mg/kg x 1 dose, then 6 mg/kg q3wks x 11 doses Adjuvant chemotherapy, post-op radiation and hormonal therapy at discretion of treating physicians<br>|
| Experimental: Adjuvant cohort 2<br> | Drug: Cohort 2 adjuvant<br>* Trastuzumab 8 mg/kg x 1 dose, then 6 mg/kg q3wks x 11 doses Adjuvant chemotherapy, post-op radiation and hormonal therapy at discretion of treating physicians<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Complete Pathologic Response Rate, Observed Following Treatment With q3week Carboplatin, Weekly Abraxane and Weekly Trastuzumab in Resectable and Unresectable LABC; | These numbers represent patients with a RCB score of zero (0). RCB stands for residual cancer burden. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients Affected by Toxicities of Regimen During Treatment, Including Grade >2 Neurotoxicity the Incidence of Subclinical and Clinical Cardiac Toxicity | Please note that these events represent toxicities that were experienced during treatment, but that does not mean that all toxicities were indeed deemed related to study treatment. | 1 year | 

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