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

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

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%.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Abraxane; Drug: Carboplatin; Drug: Avastin

Detailed Description

See above brief summary

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Bridgeport, Connecticut, United States, 06610
      • Bridgeport Hospital
    • New Haven, Connecticut, United States, 06519
      • Yale Smilow Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hospital
    • Providence, Rhode Island, United States, 02905
      • Women and Infants
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hsopital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Abraxane; Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks; Other Names: Paclitaxel Protein-Bound; Drug: Carboplatin; Carboplatin at AUC 6 over 30 min IV weeks 1,4,7, and 10; Other Names: Paraplatin; 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); Other Names: Bevacizumab
Experimental: 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	Drug: Abraxane; Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks; Other Names: Paclitaxel Protein-Bound; Drug: Carboplatin; Carboplatin at AUC 6 over 30 min IV weeks 1,4,7, and 10; Other Names: Paraplatin; 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); Other Names: Bevacizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: William Sikov MD
• Collaborators: Yale University
• Investigators: Principal Investigator: William Sikov, MD, Brown University

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): May 15, 2014
• Study Completion (Actual): May 15, 2014

Study Registration Dates

• First Submitted: July 15, 2008
• First Submitted That Met QC Criteria: July 24, 2008
• First Posted (Estimate): July 28, 2008

Study Record Updates

• Last Update Posted (Actual): April 29, 2021
• Last Update Submitted That Met QC Criteria: April 6, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Breast Cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Carboplatin; Paclitaxel; Bevacizumab; Albumin-Bound Paclitaxel
• Other Study ID Numbers: BrUOG-BR-211A