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

NCT ID: NCT00723125

Last Updated: 2021-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2014-05-15

Brief Summary

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

See above brief summary

Conditions

Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

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

Group Type: EXPERIMENTAL

Abraxane

Intervention Type: DRUG

Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks

Carboplatin

Intervention Type: DRUG

Carboplatin at AUC 6 over 30 min IV weeks 1,4,7, and 10

Avastin

Intervention Type: DRUG

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)

Cohort 2

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

Group Type: EXPERIMENTAL

Abraxane

Intervention Type: DRUG

Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks

Carboplatin

Intervention Type: DRUG

Carboplatin at AUC 6 over 30 min IV weeks 1,4,7, and 10

Avastin

Intervention Type: DRUG

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)

Interventions

Abraxane

Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks

Intervention Type: DRUG

Carboplatin

Carboplatin at AUC 6 over 30 min IV weeks 1,4,7, and 10

Intervention Type: DRUG

Avastin

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)

Intervention Type: DRUG

Other Intervention Names

Paclitaxel Protein-Bound; Paraplatin; Bevacizumab

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Yale University

OTHER

Sponsor Role: collaborator

William Sikov MD

OTHER

Sponsor Role: lead

Responsible Party

William Sikov MD

Principle Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

William Sikov, MD

Role: PRINCIPAL_INVESTIGATOR

Brown University

Locations

Bridgeport Hospital

Bridgeport, Connecticut, United States

Yale Smilow Cancer Center

New Haven, Connecticut, United States

Rhode Island Hsopital

Providence, Rhode Island, United States

Women and Infants

Providence, Rhode Island, United States

The Miriam Hospital

Providence, Rhode Island, United States

Countries

United States

Other Identifiers

BrUOG-BR-211A

Identifier Type: -

Identifier Source: org_study_id