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

NCT ID: NCT00542451

Last Updated: 2024-06-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 406 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2022-08-30

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.

Conditions

Breast Cancer; Carcinoma of the Breast

Study Design

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

Study Groups

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

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.

Group Type: EXPERIMENTAL

Paclitaxel

Intervention Type: DRUG

Every week for 12 weeks

Trastuzumab

Intervention Type: DRUG

Once a week for twelve weeks Then once a week or once every three weeks for 40 weeks

Interventions

Paclitaxel

Every week for 12 weeks

Intervention Type: DRUG

Trastuzumab

Once a week for twelve weeks Then once a week or once every three weeks for 40 weeks

Intervention Type: DRUG

Other Intervention Names

Taxol; Herceptin

Eligibility Criteria

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.

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

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: collaborator

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Sara Tolaney, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sara Tolaney, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

University of California-San Francisco

San Francisco, California, United States

Loyola University Medical Center

Maywood, Illinois, United States

Indiana University

Indianapolis, Indiana, United States

John Hopkins University

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana-Farber at Faulkner Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Cape Cod Healthcare

Hyannis, Massachusetts, United States

Lowell General Hospital

Lowell, Massachusetts, United States

North Shore Medical Center

Peabody, Massachusetts, United States

Washington University

St Louis, Missouri, United States

North Shore LIJ Health System Monter Cancer Center

Lake Success, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Weill Cornell Medical College

New York, New York, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Case Western University

Cleveland, Ohio, United States

Tennessee Oncology

Nashville, Tennessee, United States

University of Vermont Cancer Center

Burlington, Vermont, United States

Countries

United States

References

Tolaney SM, Tarantino P, Graham N, Tayob N, Pare L, Villacampa G, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis MJ, Shapira I, Wolff AC, Carey LA, Barroso-Sousa R, Villagrasa P, DeMeo M, DiLullo M, Zanudo JGT, Weiss J, Wagle N, Partridge AH, Waks AG, Hudis CA, Krop IE, Burstein HJ, Prat A, Winer EP. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trial. Lancet Oncol. 2023 Mar;24(3):273-285. doi: 10.1016/S1470-2045(23)00051-7.

Reference Type: DERIVED

PMID: 36858723 (View on PubMed)

Tolaney SM, Guo H, Pernas S, Barry WT, Dillon DA, Ritterhouse L, Schneider BP, Shen F, Fuhrman K, Baltay M, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis MJ, Shapira I, Wolff AC, Carey LA, Overmoyer B, Partridge AH, Hudis CA, Krop IE, Burstein HJ, Winer EP. Seven-Year Follow-Up Analysis of Adjuvant Paclitaxel and Trastuzumab Trial for Node-Negative, Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer. J Clin Oncol. 2019 Aug 1;37(22):1868-1875. doi: 10.1200/JCO.19.00066. Epub 2019 Apr 2.

Reference Type: DERIVED

PMID: 30939096 (View on PubMed)

Barroso-Sousa R, Barry WT, Guo H, Dillon D, Tan YB, Fuhrman K, Osmani W, Getz A, Baltay M, Dang C, Yardley D, Moy B, Marcom PK, Mittendorf EA, Krop IE, Winer EP, Tolaney SM. The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial. Ann Oncol. 2019 Apr 1;30(4):575-581. doi: 10.1093/annonc/mdz047.

Reference Type: DERIVED

PMID: 30753274 (View on PubMed)

Tolaney SM, Barry WT, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis M, Shapira I, Wolff AC, Carey LA, Overmoyer BA, Partridge AH, Guo H, Hudis CA, Krop IE, Burstein HJ, Winer EP. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med. 2015 Jan 8;372(2):134-41. doi: 10.1056/NEJMoa1406281.

Reference Type: DERIVED

PMID: 25564897 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

07-199

Identifier Type: -

Identifier Source: org_study_id