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

William Sikov MD

Status and phase: Completed; Phase 2

Conditions: Breast Cancer

Treatments: Drug: Abraxane; Drug: Carboplatin; Drug: Avastin

Study type: Interventional

Funder types: Other

Identifiers

NCT00723125

BrUOG-BR-211A

Details and patient eligibility

About

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%.

Full description

See above brief summary

Enrollment: 60 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Cohort 1

Experimental group

Description:

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

Treatment:

Drug: Avastin

Drug: Carboplatin

Drug: Abraxane

Cohort 2

Experimental group

Description:

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

Treatment:

Drug: Avastin

Drug: Carboplatin

Drug: Abraxane