Neoadjuvant Carboplatin, Weekly Abraxane and Trastuzumab in HER2+ Breast Cancer

NCT ID: NCT00617942

Last Updated: 2020-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2015-12-31

Brief Summary

Q3week carboplatin with weekly abraxane and trastuzumab as neoadjuvant therapy in resectable and unresectable HER2+ (stage IIa-IIIb) breast cancer

Detailed Description

Our goal is to develop an induction chemotherapy regimen that will have a pCR rate above 50% in HER2+ patients without exposing patients to the toxicity of an anthracycline-based regimen. A minimum of 60 evaluable patients will be accrued to the study. We are assuming an observed pCR (or near pCR) rate of 70%. Assuming no more than 10% of patients will be inevaluable for the primary endpoint (pCR), we will have at least 54 evaluable patients. With this number, we will have 90% power, with a 1-sided alpha error of 0.05, to demonstrate a pCR rate exceeding 50% for our novel regimen.

Conditions

Breast Cancer

Study Design

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

Study Groups

Neo-adjuvant cohort 1

Group Type: EXPERIMENTAL

Cohort 1 neo-adjuvant

Intervention Type: DRUG

Cohort 1 : Trastuzumab 6 mg/kg IV over 60 minutes day -14

Trastuzumab 2 mg/kg IV over 60 minutes weekly then Abraxane 100 mg/m2 IV over 30 minutes weekly x 18 weeks followed by Carboplatin at AUC 6 IV over 30 min weeks 1,4,7,10,13 and 16

Neo-adjuvant cohort 2

Group Type: EXPERIMENTAL

Cohort 2 neo-adjuvant

Intervention Type: DRUG

Cohort 2 :Abraxane 100 mg/m2 IV over 30 minutes days -14 and -7 Trastuzumab 2 mg/kg IV over 60 minutes weekly (4 mg/kg week 1) then Abraxane 100 mg/m2 IV over 30 minutes weekly x 18 weeks followed by Carboplatin at AUC 6 IV over 30 min weeks 1,4,7,10,13 and 16

Adjuvant cohort 1

Group Type: EXPERIMENTAL

Cohort 1 adjuvant

Intervention Type: DRUG

Trastuzumab 8 mg/kg x 1 dose, then 6 mg/kg q3wks x 11 doses Adjuvant chemotherapy, post-op radiation and hormonal therapy at discretion of treating physicians

Adjuvant cohort 2

Group Type: EXPERIMENTAL

Cohort 2 adjuvant

Intervention Type: DRUG

Trastuzumab 8 mg/kg x 1 dose, then 6 mg/kg q3wks x 11 doses Adjuvant chemotherapy, post-op radiation and hormonal therapy at discretion of treating physicians

Interventions

Cohort 1 neo-adjuvant

Cohort 1 : Trastuzumab 6 mg/kg IV over 60 minutes day -14

Trastuzumab 2 mg/kg IV over 60 minutes weekly then Abraxane 100 mg/m2 IV over 30 minutes weekly x 18 weeks followed by Carboplatin at AUC 6 IV over 30 min weeks 1,4,7,10,13 and 16

Intervention Type: DRUG

Cohort 2 neo-adjuvant

Cohort 2 :Abraxane 100 mg/m2 IV over 30 minutes days -14 and -7 Trastuzumab 2 mg/kg IV over 60 minutes weekly (4 mg/kg week 1) then Abraxane 100 mg/m2 IV over 30 minutes weekly x 18 weeks followed by Carboplatin at AUC 6 IV over 30 min weeks 1,4,7,10,13 and 16

Intervention Type: DRUG

Cohort 1 adjuvant

Trastuzumab 8 mg/kg x 1 dose, then 6 mg/kg q3wks x 11 doses Adjuvant chemotherapy, post-op radiation and hormonal therapy at discretion of treating physicians

Intervention Type: DRUG

Cohort 2 adjuvant

Trastuzumab 8 mg/kg x 1 dose, then 6 mg/kg q3wks x 11 doses Adjuvant chemotherapy, post-op radiation and hormonal therapy at discretion of treating physicians

Intervention Type: DRUG

Other Intervention Names

Abraxane (nab-paclitaxel), Herceptin (trastuzumab) and carboplatin

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 < or = ULN
• No evidence of metastatic disease Not pregnant or lactating
• No prior systemic therapy for this breast cancer
• Serum Creatinine < 1.5 mg/dl or Creat Cl > 30 ml/min
• Serum ALT < 2.5 x ULN
• ER, PR and HER2 status required
• LVEF (MUGA/echo)WNL
• No baseline > 2 neuropathy
• Hemoglobin > 9.0 gm/dl
• HER2+, defined by IHC 3+ or FISH ratio > 2.0

• 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

City of Hope

Duarte, California, United States

Yale Smilow Cancer Center

New Haven, Connecticut, United States

Women and Infants Hospital

Providence, Rhode Island, United States

Roger Williams Medical Center

Providence, Rhode Island, United States

Rhode Island and The Miriam Hospital

Providence, Rhode Island, United States

Countries

United States

References

Cheng H, Bai Y, Sikov W, Sinclair N, Bossuyt V, Abu-Khalaf MM, Harris LN, Rimm DL. Quantitative measurements of HER2 and phospho-HER2 expression: correlation with pathologic response to neoadjuvant chemotherapy and trastuzumab. BMC Cancer. 2014 May 8;14:326. doi: 10.1186/1471-2407-14-326.

Reference Type: DERIVED

PMID: 24885187 (View on PubMed)

Other Identifiers

BrUOG-BR-211B

Identifier Type: -

Identifier Source: org_study_id