Phase II Neoadjuvant Trial of Trastuzumab in Combination With Dose-Dense ABI-007 (Abraxane™)

NCT ID: NCT00503750

Last Updated: 2012-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2011-07-31

Brief Summary

This is a phase II one arm study. Patients with HER2 (Human Epidermal Growth Factor Receptor 2)positive early stage breast cancer will receive ABI-007 and vinorelbine in combination with trastuzumab before having breast surgery.

Detailed Description

This is a phase II one arm study. Patients with HER2(Human Epidermal Growth Factor Receptor 2) positive early stage breast cancer will receive ABI-007 and vinorelbine in combination with trastuzumab before having breast surgery.

Approximately 50 patients will take part at multi-sites with potentially 20 patients participating at the Emory Winship Cancer Institute, Grady Memorial Hospital, and Emory Crawford Long Hospital in Atlanta, Georgia.

Conditions

Breast Cancer

Study Design

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

Study Groups

Trastuzumab and Abraxane followed Trastuzumab and Vinorelbine

Patients will be treated sequentially with preoperative trastuzumab and dose-dense ABI-007 followed by trastuzumab in combination with vinorelbine. Trastuzumab will be administered as a one-time loading dose of 4 mg/kg as a 90 minute infusion, followed by 20 weekly treatments at 2 mg/kg as a 30 minute infusion. ABI-007 will be administered every 2 weeks at a dose of 260mg/m2 as 30 minute infusion on the same days as trastuzumab for a total of 4 cycles (weeks 1 -8). Growth factor support with pegfilgrastim (Neulasta®) is required 24 to 48 hours following completion of each cycle of ABI-007. Beginning week 9, patients will then receive weekly vinorelbine at a dose of 25mg/m2 for 12 weeks on the same day as trastuzumab for a total of 4 cycles (weeks 9-20). As per standard treatment of HER2-positive breast cancers, patients will continue to receive trastuzumab every 3 weeks at 6 mg/kg beginning week 21 through week 52.

Group Type: ACTIVE_COMPARATOR

Pre operativeTrastuzumab

Intervention Type: DRUG

Trastuzumab one-time loading dose of 4 mg/kg as 90 minute infusion, followed by 20 weekly treatments at 2 mg/kg as 30 minute infusion.

As per standard treatment of HER2-positive breast cancers, patients will continue to receive trastuzumab every 3 weeks at 6 mg/kg beginning week 21 through week 52.

ABI-007 (Abraxane)

Intervention Type: DRUG

ABI-007 will be administered every 2 weeks at a dose of 260mg/m2 as 30 minute infusion on the same days as trastuzumab for a total of 4 cycles (weeks 1 -8).

Vinorelbine

Intervention Type: DRUG

Beginning week 9, patients will then receive weekly vinorelbine at a dose of 25mg/m2 for 12 weeks on the same day as trastuzumab for a total of 4 cycles (weeks 9-20).

Interventions

Pre operativeTrastuzumab

Trastuzumab one-time loading dose of 4 mg/kg as 90 minute infusion, followed by 20 weekly treatments at 2 mg/kg as 30 minute infusion.

As per standard treatment of HER2-positive breast cancers, patients will continue to receive trastuzumab every 3 weeks at 6 mg/kg beginning week 21 through week 52.

Intervention Type: DRUG

ABI-007 (Abraxane)

ABI-007 will be administered every 2 weeks at a dose of 260mg/m2 as 30 minute infusion on the same days as trastuzumab for a total of 4 cycles (weeks 1 -8).

Intervention Type: DRUG

Vinorelbine

Beginning week 9, patients will then receive weekly vinorelbine at a dose of 25mg/m2 for 12 weeks on the same day as trastuzumab for a total of 4 cycles (weeks 9-20).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed invasive breast carcinoma.
• Early stage breast cancer - stage I (tumor size greater than 1 cm), II and IIA.
• 3+ HER2 overexpression by IHC or 2+ HER2 overexpression and FISH positivity.
• Patients must have measurable disease as defined by palpable lesion with both diameters greater than or equal to 1 cm measurable with caliper and/or a positive mammogram or ultrasound with at least one dimension greater than or equal to 1 cm. Bilateral mammogram and clip placement is required for study entry. Baseline measurements of the indicator lesions must be recorded on the patient registration form. To be valid for baseline, the measurements must have been made within the 14 days (4-6 weeks for x-rays and scans) immediately preceding patient's entry in study.
• ECOG performance status 0 to 2 within 14 days of study entry.
• Normal (greater than 50%) left ventricular ejection fraction (LVEF) by MUGA scan or echocardiography.
• Must be 18 years of age or older.
• Women or men of childbearing potential must use a reliable and appropriate contraceptive method. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
• Final eligibility for a clinical trial is determined by the health professionals conducting the trial.

Exclusion Criteria

• Evidence of disease outside the breast or chest wall, except ipsilateral axillary lymph nodes.
• Prior chemotherapy, hormonal therapy, biologic therapy or radiation therapy for breast cancer. Patients with history of DCIS are eligible if they were treated with surgery alone.
• Medical, psychological, or surgical condition which the investigator feels might compromise study participation.
• Pregnant or lactating women are not eligible.
• Patients with history of previous or current malignancy at other sites with the exception of adequately treated carcinoma in situ of the cervix or basal or squamous cell carcinoma of the skin. Patients with a history of other malignancies who remain disease free for greater than five years are eligible.
• Evidence of sensory and/or peripheral neuropathy.
• Serious, uncontrolled, concurrent infections.
• Major surgery within 4 weeks of the start of study treatment without complete recovery.
• Final eligibility for a clinical trial is determined by the health professionals conducting the trial.

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

Sponsors

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Ruth O'Regan

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ruth O'Regan, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University Winship Cancer Institute

Locations

Piedmont Hospital Research Institute

Atlanta, Georgia, United States

Emory University Winship Cancer Institute

Atlanta, Georgia, United States

Countries

United States

Other Identifiers

0495-2006

Identifier Type: -

Identifier Source: org_study_id