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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ruth O'Regan, Emory University
ClinicalTrials.gov Identifier:
NCT00503750
First received: July 17, 2007
Last updated: June 16, 2012
Last verified: June 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Breast Cancer
 Drug: Pre operativeTrastuzumab
Drug: ABI-007 (Abraxane)
Drug: Vinorelbine
 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: Phase II Neoadjuvant Trial of Trastuzumab in Combination With Dose-Dense ABI-007 (Abraxane™) Followed by Vinorelbine for HER2 Overexpressing Early Stage Breast Cancer

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Emory University:

Primary Outcome Measures:
  • Number of Participants With Complete Pathologic Response. [ Time Frame: assess at 8 weeks ] [ Designated as safety issue: Yes ]

    Pathologic complete response (pCR): Absence of invasive breast cancer in the breast (mastectomy or lumpectomy) specimen at the time of definitive surgery. Presence of in situ cancer alone will be considered a pCR.

    Although clinical examination is the primary method of determining response, radiologic assessments (mammogram, ultrasound ± MRI) may be used to confirm response/non-response.



Secondary Outcome Measures:
  • Number of Participants Who Had Complete Clinical Resposnse, Partial Response and Stable Disease. [ Time Frame: clinic examination every 2 weeks, evaluated every 3 months for 2 years post-op ] [ Designated as safety issue: Yes ]

    Complete clinical response (CCR): complete disappearance of all measurable malignant disease. No new malignant lesion, disease-related symptoms or evidence of non-evaluable disease.

    Partial response (PR): Reduction by at least 50% of the sum of the products of the longest perpendicular diameters of all measurable lesions.

    Stable disease (SD): For bidimensionally measurable disease, no decrease or <25% increase in the sum of the products of the longest perpendicular diameters of all measurable lesions.



Enrollment: 27
Study Start Date: April 2008
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
 Drug: 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.

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).
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).

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00503750

Locations
United States, Georgia
Emory University Winship Cancer Institute
Atlanta, Georgia, United States, 30322
Piedmont Hospital Research Institute
Atlanta, Georgia, United States, 30309
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Ruth O'Regan, MD Emory University Winship Cancer Institute
  More Information

No publications provided

Responsible Party: Ruth O'Regan, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT00503750     History of Changes
Other Study ID Numbers: 0495-2006
Study First Received: July 17, 2007
Results First Received: March 26, 2012
Last Updated: June 16, 2012
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Emory University:
Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Vinorelbine
Vinblastine
Paclitaxel
Trastuzumab
 Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 23, 2013