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: July 15, 2014
Last verified: July 2014

July 15, 2008
July 15, 2014
September 2008
June 2014   (final data collection date for primary outcome measure)
pathological response rates at surgery [ Time Frame: at surgery approximately 5 months after initail treatment ] [ Designated as safety issue: No ]
To determine clinical & path. resp. rates, particularly pCR/near pCR rate,in HER2(-) stage IIA-IIIB Br. Ca with add. of Avastin 10 mg/kg q2weeks to either carboplatin/weekly Abraxane follow by ddAC (cohort1)or carboplatin/weekly Abraxane alone(cohort2). [ Time Frame: Prospective ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00723125 on ClinicalTrials.gov Archive Site
Measure of Safety and Tolerability according to CTC version 3.0 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
To assess the toxicities of these regimens, and whether those toxicities affect treatment delivery, including complications of surgery [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
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%.

See above brief summary

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Breast Cancer
Drug: Cohort 1 and Cohort 2
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)
  • 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
    Intervention: Drug: Cohort 1 and Cohort 2
  • 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
    Intervention: Drug: Cohort 1 and Cohort 2
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
60
June 2014
June 2014   (final data collection date for primary outcome measure)

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
Female
19 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00723125
BrUOG-BR-211A
Yes
William Sikov, Brown University
William Sikov
Yale University
Principal Investigator: William Sikov, MD Brown University
Brown University
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP