Clinical trial NCT00542451: Adjuvant Paclitaxel and Trastuzumab for Node-Negative HER2-Positive Breast Cancer
Official title: A Phase II Trial of Adjuvant Paclitaxel and Trastuzumab for Node-Negative HER2-Positive Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Carcinoma of the Breast
Keywords: node-negative breast cancer
HER-2 positive
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
name: Beth Israel Deaconess Medical Center
name: Massachusetts General Hospital
name: Genentech, Inc.
First posted: 2007-10-11
Enrollment: 406
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 3-year Disease Free Survival (DFS) Rate
timeFrame: at 3 years
Secondary outcomes:
measure: Disease Free Survival (DFS) in Patients With Tumors Measuring ≤1 cm or > 1 cm
timeFrame: at 3 years
measure: Number of Patients With Grade III/IV Cardiac Left Ventricular Dysfunction
timeFrame: 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).
measure: Number of Patients With Grade III/IV Neurotoxicity
timeFrame: 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).
measure: Number of Patients With Amenorrhea
timeFrame: 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.
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California-San Francisco
state: California
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Baltimore
country: United States
facility: John Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber at Faulkner Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Hyannis
country: United States
facility: Cape Cod Healthcare
state: Massachusetts
city: Lowell
country: United States
facility: Lowell General Hospital
state: Massachusetts
city: Peabody
country: United States
facility: North Shore Medical Center
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Lake Success
country: United States
facility: North Shore LIJ Health System Monter Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Cleveland
country: United States
facility: Case Western University
state: Ohio
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Burlington
country: United States
facility: University of Vermont Cancer Center
state: Vermont
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Sara Tolaney, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.