Return to List

Study Summary
No. ACOSOGZ1041:.......Breast......Funda Meric-Bernstam......Surgical Oncology
.
Study Summary Title
Study Summary
Number:
ACOSOGZ1041
Study Title:A Randomized Phase III Trial Comparing a Neoadjuvant Regimen of FEC-75 Followed By Paclitaxel Plus Trastuzumab With a Neoadjuvant Regimen of Paclitaxel Plus Trastuzumab Followed by FEC-75 Plus Trastuzumab in Patients with HER-2 Positive Operable Breast Cancer
.
Physician New Patient Referral
Name:Funda Meric-BernstamPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Surgical OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-745-4453
Contact us about clinical trials
.
General Information
Disease Group:BreastSupported By:American College of Surgeons Oncology Group (ACOSOG)
Phase of Study:Phase IIIReturn
Visit:
Arm 1: Every 21 days for 4 cyc. 21 days post FEC wkly for 12 wks post surg
every 3 mths for 52 wks. Every 6 mths for 5 yrs.

Arm 2: Wkly for 12 wks. Every 21 days for 4 cyc & wkly for 12 wks post surg
every 3 mths for 52 wks. Every 6 mths for 5 yrs.
Treatment
Agents:
5-Fluorouracil
Cyclophosphamide
Epirubicin
Paclitaxel
Trastuzumab
Home Care:N/A
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
Research has shown that trastuzumab can improve survival in patients who have
tumors that have an overactive HER2 gene. The latest information suggests that
trastuzumab, when given along with chemotherapy, may help chemotherapy more
actively treat tumors.

The goal of this clinical research study is to study the effect of combining
trastuzumab and chemotherapy, compared to giving chemotherapy by itself, in
patients with breast cancer tumors that have an overactive HER2 gene.
Researchers also want to know how the heart will be affected by combining
trastuzumab with the drug combination of 5-fluorouracil (5-FU), epirubicin, and
cyclophosphamide (a combination called "FEC" therapy). Last, researchers want
to find out if results from specialized tests on the tumor tissue and blood can
tell which tumor types will be completely destroyed using the drug combinations
used in this study.
.
Study Objectives / Outcomes
Primary Objective

The primary objective of this study is to compare the pathologic complete response rate (pCR) within the breast of a sequential regimen of concurrent weekly paclitaxel and trastuzumab, followed by continued weekly trastuzumab administered concurrently with FEC-75 (Arm 2), to the pCR rate of a sequential regimen of FEC-75 alone followed by concurrent weekly paclitaxel and trastuzumab (Arm 1).

Secondary Objectives

The secondary objectives of this study are the following:
1. To estimate the cardiotoxicity of a sequential regimen of concurrent weekly paclitaxel and trastuzumab, followed by continued weekly trastuzumab administered concurrently with FEC-75, followed postoperatively by q 3 week trastuzumab for a total duration of trastuzumab therapy through 52 weeks from the first dose (Arm 2), and compare the cardiotoxicity to that of a sequential regimen of FEC-75 alone followed by concurrent weekly paclitaxel and trastuzumab, followed by q 3 week trastuzumab for a total duration of trastuzumab therapy through 52 weeks from the first dose (Arm 1).
2. To compare the combined pCR rate in the breast and ipsilateral axilla obtained with the two regimens evaluated in this study.
3. To compare the clinical response rates (cRR) of the two regimens evaluated in this study.
4. To compare the non-cardiac toxicity of the two regimens evaluated in this study.
5. To compare breast conservation rates achieved with the two regimens evaluated in this study.
6. To evaluate disease-free survival and overall survival at 5 years post-randomization.
7. To correlate pCR rate with potential molecular markers of response.
.
Study Status Information
Study Activation / Registration Date:
IRB Review and Approval Date:09/25/2007
Study Type:Phase Iii
Recruitment Status:Closed
Projected Accrual:270
.
Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Patients must be female.

2) Patients must be 18 years of age or older.

3) Patients must have an ECOG performance status of 0 or 1.

4) The diagnosis of invasive adenocarcinoma of the breast must have been made by core needle biopsy. NOTE: FNA is acceptable for evaluation of breast primaries < 2 cm and lymph node metastases.

5) Patients must have a breast primary >/= 2.0 cm and/or one or more biopsy-positive lymph nodes. Patients with prior excisional biopsy of the breast primary are eligible, provided biopsy-positive lymph nodes are present.

6) The breast cancer must be determined to be HER2-positive prior to study entry. Assays performed using fluorescent in situ hybridization (FISH) require gene amplification. Assays using immunohistochemistry (IHC) require a strongly positive (3+) staining intensity score.

7) Within 3 months prior to entry, the patient must have a baseline left ventricular ejection fraction (LVEF) measured by MUGA scan >/= 55. Note: Echocardiogram may be substituted for MUGA at baseline, but the same method of assessment should be used throughout the study.

8) At study entry a) absolute neutrophil count must be greater than or equal to 1200/mm(3); b) Platelet count must be greater than or equal to 100,000/mm(3); c) Total bilirubin must be less than or equal to the ULN for the lab unless the patient has a grade 1 bilirubin elevation (greater than ULN to 1.5 x ULN) resulting from Gilbert's disease or similar syndrome due to slow conjugation of bilirubin; d) Alkaline phosphatase must be less than or equal to 2.5 x ULN for the lab; e) AST must be less than or equal to ULN for the lab f) Serum creatinine must be less than or equal to ULN for the lab.

9) Patients with either skeletal pain or alkaline phosphatase that is greater than ULN but less than or equal to 2.5 x ULN are eligible for inclusion in the study if bone scans fail to demonstrate metastatic disease. Suspicious findings on bone scan must be confirmed as benign by x-ray, MRI or biopsy.

Exclusion Criteria:1) Patients with a history of DCIS or synchronous DCIS of the contralateral breast regardless of therapy are eligible. Those with synchronous invasive breast cancer are NOT eligible.

2) Patients with a history of ipsilateral DCIS treated by local excision with or without hormonal therapy are eligible. Those treated with radiation therapy are NOT eligible.

3) Patients with a history of non-breast malignancies are eligible if they have remained disease-free for 5 years since completing their initial treatment regimen and are deemed by their physician to be at low risk for recurrence. Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: carcinoma in situ of the cervix, colon carcinoma in situ, melanoma in situ and basal cell and squamous cell carcinoma of the skin.

4) Patients must NOT have had any surgical axillary staging procedure prior to study entry. However, patients who have had FNA of an axillary node are eligible.

5) Patients must NOT have definitive clinical or radiologic evidence of metastatic disease.

6) Patients must NOT have a prior history of invasive breast cancer

7) Patients must NOT have had treatment given for this breast cancer prior to study entry. (The only exception is hormonal therapy, which may have been given for up to a total of 28 days anytime after diagnosis and before study entry. In such a case, hormonal therapy must stop at or before study entry and be re-started, if indicated, following surgery.

8) Patients must NOT be taking any sex hormonal therapy, e.g., birth control pills, ovarian hormonal replacement therapy, etc. (Patients are eligible if this therapy is discontinued prior to study entry.) Women of reproductive potential must agree to use an effective non-hormonal method of contraception during therapy.

9) Patients must NOT be receiving therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulator (SERM), either for osteoporosis or breast cancer prevention. (Patients are eligible only if these medications are discontinued prior to study entry.)

10) Patients must NOT have had prior therapy with anthracyclines or taxanes for any malignancy.

11) Patients must NOT have non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude treatment with either of the treatment regimens.

12) Patients must NOT have cardiac disease that would preclude the use of epirubicin or trastuzumab. This includes active cardiac disease a) angina pectoris that requires the use of antianginal medication; cardiac arrythmia requiring medication; b) severe conduction abnormality; c) clinically significant valvular disease; d) cardiomegaly on chest x-ray; e) ventricular hypertrophy on EKG; or f) patients with poorly controlled hypertension, i.e., diastolic greater than 100 mm/Hg. (Patients with hypertension that is well controlled on medication are eligible).

13) CONTINUED FROM EXCLUSION 14 - History of cardiac disease g) myocardial infarction documented as a clinical diagnosis or by EKG or any other tests h) documented congestive heart failure; i) documented cardiomyopathy.

14) Patients must NOT have sensory/motor neuropathy greater than or equal to grade 2, as defined by the NCI's Common Terminology Criteria for Adverse Events Version 3.0.

15) Patients must NOT have had administration of any investigational agents within 30 days before study entry.

16) Women of child-bearing potential must have a negative urine or serum pregnancy test within 2 weeks of registration. Women who are breast feeding are NOT eligible.

17) Patients must NOT have psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements.

.
Links
Registration Number: NCT00513292
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
.
Results


Return to Clinical Trials at M.D. Anderson Cancer Center