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

Phase 2

Completed

• Conditions: Breast Cancer; Carcinoma of the Breast
• Interventions: Drug: Paclitaxel; Drug: Trastuzumab

• Registration Number: NCT00542451
• Lead Sponsor: Dana-Farber Cancer Institute

Brief Summary

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

* 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.

Study Timeline

• Study Start: 2007-10
• Study First Submitted: 2007-10-09
• Study First Submitted QC: 2007-10-09
• Study First Posted: 2007-10-11
• Primary Completion: 2014-04-21
• Study Completion: 2022-08-30
• Results First Submitted: 2022-11-01
• Results First Submitted QC: 2023-03-24
• Results First Posted: 2023-03-27
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-24
• Last Update Posted: 2024-06-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 406

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

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Adjuvant Paclitaxel and Trastuzumab for Node-Negative HER2-Positive Breast Cancer	Trastuzumab	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.
Adjuvant Paclitaxel and Trastuzumab for Node-Negative HER2-Positive Breast Cancer	Paclitaxel	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.

Primary Outcome Measures

Name	Time	Method
3-year Disease Free Survival (DFS) Rate	at 3 years	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.

Secondary Outcome Measures

Name	Time	Method
Number of Patients With Amenorrhea	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.	Patients that eligible for amenorrhea assessment and data collecting will be evaluated by standard method defined per protocol 3.9, through menses assessment survey.
Disease Free Survival (DFS) in Patients With Tumors Measuring ≤1 cm or > 1 cm	at 3 years	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.
Number of Patients With Grade III/IV Cardiac Left Ventricular Dysfunction	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).	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.
Number of Patients With Grade III/IV Neurotoxicity	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).	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.

Trial Locations

Locations (20)

Case Western University; 🇺🇸 Cleveland, Ohio, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Loyola University Medical Center; 🇺🇸 Maywood, Illinois, United States

John Hopkins University; 🇺🇸 Baltimore, Maryland, United States

Weill Cornell Medical College; 🇺🇸 New York, New York, United States

Dana-Farber at Faulkner Hospital; 🇺🇸 Boston, Massachusetts, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Lowell General Hospital; 🇺🇸 Lowell, Massachusetts, United States

Cape Cod Healthcare; 🇺🇸 Hyannis, Massachusetts, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

North Shore Medical Center; 🇺🇸 Peabody, Massachusetts, United States

Washington University; 🇺🇸 Saint Louis, Missouri, United States

North Shore LIJ Health System Monter Cancer Center; 🇺🇸 Lake Success, New York, United States

University of Vermont Cancer Center; 🇺🇸 Burlington, Vermont, United States

Indiana University; 🇺🇸 Indianapolis, Indiana, United States

University of California-San Francisco; 🇺🇸 San Francisco, California, United States

Duke Comprehensive Cancer Center; 🇺🇸 Durham, North Carolina, United States

Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States