Adjuvant Paclitaxel and Trastuzumab for Node-Negative HER2-Positive Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study is to find out what effect the postoperative combination of therapies: trastuzumab (herceptin) and paclitaxel (taxol) will have on breast cancer recurrence. A combination of trastuzuamb and chemotherapy has been used in women with node positive and high risk node negative disease. This tests utilizes a well tolerated regimen of weekly paclitaxel and trastuzumab in women with T1, node negative tumors that are HER2 positive. We would like to determine how effective this drug combination is when used in women with early stage breast cancer, as well as to better define the side effects of this treatment.

Detailed Description
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Participants will enroll in this study at the time they are starting their adjuvant therapy for breast cancer. Participants will receive chemotherapy with paclitaxel every week for 12 weeks. They will begin to receive trastuzumab at the same time they begin paclitaxel. Once they have completed the 12 weeks of paclitaxel and trastuzumab, they will receive trastuzumab every 3 weeks or weekly for 40 weeks. Participants will be followed with routine assessments such as physical exam and vital signs every 3 months for the first year, and then every 6 months for years 2-5. Then we would like to keep track of the participants medical condition by calling them on the telephone once per year.

Official Title
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A Phase II Trial of Adjuvant Paclitaxel and Trastuzumab for Node-Negative HER2-Positive Breast Cancer

Conditions
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Breast Cancer, Carcinoma of the Breast

Intervention / Treatment
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* Drug: Paclitaxel
* Drug: Trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed invasive carcinoma of the breast Tumors must be less than or equal to 3cm in greatest dimension Must have node-negative breast cancer according to teh AJCC 7th edition ER/PR determination is required. ER- and PR-assays should be performed by immunohistochemical methods HER-2 positive: IHC 3+ or FISH >2 Bilateral breast cancers that individually meet eligibility criteria are allowed Patients should have tumor tissue available, and a tissue block of sufficient size to make 15 slides must be sent to DFCI for testing Less than or equal to 84 days from mastectomy or from axillary dissection or sentinel node biopsy if the patient's most extensive breast surgery was a breast-sparing procedure All tumor should be removed by either a modified radical mastectomy or a segmental mastectomy (lumpectomy), with either a sentinel node biopsy or axillary dissection 18 years of age or older ECOG Performance Status of 0 or 1 Adequate bone marrow function, hepatic function, and renal function as outlined in protocol Left ventricular ejection fraction of greater than or equal to 50% Willingness to discontinue any hormonal agent prior to registration and while on study Willingness to discontinue sex hormonal therapy, e.g. birth control pills, prior to registration and while on study Patients with a history of ipsilateral DCIS are eligible if they were treated with wide-excision alone, without radiation therapy Patients undergoing breast conservation therapy must not have any contraindications to radiation therapy Exclusion Criteria: Pregnant or nursing women Locally advanced tumors at diagnosis, including tumors fixed to the chest wall, peau d'orange, skin ulcerations/nodules, or clinical inflammatory changes History of prior chemotherapy in past 5 years History of prior trastuzumab therapy Active, unresolved infection Prior history of any other malignancy in the past 5 years, except for early stage tumors of the skin or cervix treated with curative intent Sensitivity to benzyl alcohol Grade 2 or greater neuropathy per NCI's CTCAv3.0. (Exception: Any chronic neurologic disorder will be looked at on a case-by-case basis by the study chair). Active cardiac disease as outlined in protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adjuvant Paclitaxel and Trastuzumab for Node-Negative HER2-Positive Breast Cancer<br>80 mg of paclitaxel per square meter of body-surface area weekly for 12 weeks and a loading dose of 4 mg of intravenous trastuzumab per kilogram of body weight on day 1, followed by 2 mg per kilogram weekly, for a total of 12 doses. After the completion of 12 weeks of treatment with Trastuzumab, the dosing of Trastuzumab could be continued on a weekly basis, or the regimen could be changed to 6 mg per kilogram every 3 weeks for 40 weeks to complete a full year of intravenous treatment with trastuzumab. | Drug: Paclitaxel<br>* Every week for 12 weeks<br>* Other names: Taxol;Drug: Trastuzumab<br>* Once a week for twelve weeks Then once a week or once every three weeks for 40 weeks<br>* Other names: Herceptin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year Disease Free Survival (DFS) Rate | Disease-free survival (DFS) is the proportion of participants ramaing disease free at 3 years based on the Kaplan-Meier method. DFS is defined to end at the time of the first of the following events: local/regional ipsilateral invasive recurrence (or ipsilateral invasive new primary), contralateral invasive breast cancer, distant recurrence, or death from any cause. | at 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Free Survival (DFS) in Patients With Tumors Measuring ≤1 cm or > 1 cm | DFS is defined as the time from registration to the first of the following events: local/regional ipsilateral invasive recurrence (or ipsilateral invasive new primary), contralateral invasive breast cancer, distant recurrence, or death from any cause. Patients without an event are censored at the date of last evaluation. | at 3 years | 
| Number of Patients With Grade III/IV Cardiac Left Ventricular Dysfunction | cardiac left ventricular dysfunction related adverse events (AE) with any attribution of possibly, probably or definite based on CTCAEv3 as reported on case report forms were counted. | AE evaluated on treatment every week during paclitaxel and every 9 weeks during trastuzumab monotheryapy, and at progression, and observation years 2-10. Median treatment duration was 11.4 months (range 0 - 23.5 months). | 
| Number of Patients With Grade III/IV Neurotoxicity | Nervous system disorders related adverse events (AE) with any attribution of possibly, probably or definite based on CTCAEv3 as reported on case report forms were counted. | AE evaluated on treatment every week during paclitaxel and every 9 weeks during trastuzumab monotheryapy, and at progression, and observation years 2-10. Median treatment duration was 11.4 months (range 0 - 23.5 months). | 
| Number of Patients With Amenorrhea | Patients that eligible for amenorrhea assessment and data collecting will be evaluated by standard method defined per protocol 3.9, through menses assessment survey. | Menses Assessment survey on Q6 months x 1 year, then q6months for year 2 and at progression, and observation years 2-10 or until progression. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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node-negative breast cancer, HER-2 positive