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

This study has been completed.
Sponsor:
Collaborator:
Yale University
Information provided by (Responsible Party):
William Sikov, Brown University
ClinicalTrials.gov Identifier:
NCT00723125
First received: July 15, 2008
Last updated: August 12, 2014
Last verified: August 2014
  Purpose

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%.


Condition Intervention Phase
Breast Cancer
Drug: Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks
Drug: Carboplatin at AUC 6 over 30 min IV weeks 1,4,7, and 10
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)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Brown University:

Primary Outcome Measures:
  • Pathological Complete Response Rates at Surgery [ Time Frame: at surgery approximately 5 months after initial treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Measure of Safety and Tolerability According to CTC Version 3.0 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 60
Study Start Date: September 2008
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 100 mg/m2 IV over 30 minutes weekly x 12 weeks Drug: Carboplatin at AUC 6 over 30 min IV weeks 1,4,7, and 10 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)
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, and 10 (in Cohort 2, omit dose of Avastin on week 10) 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 100 mg/m2 IV over 30 minutes weekly x 12 weeks Drug: Carboplatin at AUC 6 over 30 min IV weeks 1,4,7, and 10 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)

Detailed Description:

See above brief summary

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00723125

Locations
United States, Connecticut
Bridgeport Hospital
Bridgeport, Connecticut, United States, 06610
Yale Smilow Cancer Center
New Haven, Connecticut, United States, 06519
United States, Rhode Island
Women and Infants
Providence, Rhode Island, United States
The Miriam Hospital
Providence, Rhode Island, United States, 02906
Rhode Island Hsopital
Providence, Rhode Island, United States, 02903
Sponsors and Collaborators
William Sikov
Yale University
Investigators
Principal Investigator: William Sikov, MD Brown University
  More Information

No publications provided

Responsible Party: William Sikov, Principle Investigator, Brown University
ClinicalTrials.gov Identifier: NCT00723125     History of Changes
Other Study ID Numbers: BrUOG-BR-211A
Study First Received: July 15, 2008
Results First Received: July 17, 2014
Last Updated: August 12, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Brown University:
Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Bevacizumab
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014