Multimodality Treatment for Women With Stage II, Stage III, or Stage IV Breast Cancer

Breast Cancer Clinical Trial

— NRR  

Official title:

Nonrandomized Ph II Study of Multimodality Therapy for Stg IIB, IIIA/B, or Initially Presenting Stg IV Breast Cancer w/ Four Cycles of AC Followed by 12 Weeks of Single Agent Paclitaxel w/ or w/o Herceptin Followed by Local Therapy Followed by Weekly Herceptin or No Additional Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006110
• Other study ID #: LCCC 9818
• Secondary ID: UNC-9818NCI-G00-
• Status: Completed
• Phase: Phase 2
• First received: August 3, 2000
• Last updated: January 20, 2016
• Start date: December 1998
• Est. completion date: April 2013

Study information

• Verified date: January 2016
• Source: UNC Lineberger Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining chemotherapy, monoclonal antibody therapy, and surgery may be a more effective treatment for breast cancer.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy, monoclonal antibody therapy, and surgery in treating women who have stage II, stage III, or stage IV breast cancer.

Description:

OBJECTIVES:

• Determine the cardiac and other toxicity of paclitaxel when administered with trastuzumab (Herceptin) after doxorubicin and cyclophosphamide in women with stage IIB, IIIA, IIIB, IIIC, or previously untreated stage IV breast cancer.

• Determine whether the addition of paclitaxel with or without trastuzumab to conventional breast cancer adjuvant therapy (doxorubicin and cyclophosphamide) further decreases tumor size and the number of positive axillary nodes in these patients.

• Determine the 5-year disease-free survival and overall survival of patients treated with these regimens.

• Determine whether the initial pathologic response in patients receiving neoadjuvant therapy correlates with the eventual 5-year disease-free survival or overall survival.

• Compare the number of patients eligible for breast-conserving cancer surgery after treatment with doxorubicin and cyclophosphamide vs paclitaxel and trastuzumab.

• Correlate clinical and radiographic response rate with pathologic response rate in the primary tumor and axillary lymph nodes and determine which parameter best determines the pathologic response rate in patients treated with these regimens.

OUTLINE: Patients are assigned to receive either neoadjuvant therapy (HER-2 overexpressing and nonoverexpressing patients) or adjuvant therapy (HER-2 overexpressing patients only).

• Neoadjuvant therapy: Patients assigned to receive neoadjuvant therapy receive one of two treatment regimens.

• Regimen I (HER-2 nonoverexpressing patients or HER-2 overexpressing patients who refuse trastuzumab (Herceptin) therapy): Patients receive doxorubicin IV and cyclophosphamide IV over 30 minutes and paclitaxel IV over 3 hours on day 1 every 3 weeks for a total of 4 courses. Patients then undergo surgery with or without adjuvant radiotherapy and/or oral tamoxifen.

• Regimen II (HER-2 overexpressing patients only): Patients receive doxorubicin and cyclophosphamide as in regimen I. After completion of course 4, patients receive paclitaxel IV and trastuzumab IV over 90-150 minutes weekly on weeks 13-24. Patients then undergo surgery with or without adjuvant radiotherapy. Patients then receive trastuzumab IV over 30 minutes weekly on weeks 29-69 if they did not receive radiotherapy or on weeks 36-76 if they did receive radiotherapy.

• Adjuvant therapy: Patients who are assigned to receive adjuvant therapy (HER-2 overexpressing patients only) receive doxorubicin IV and cyclophosphamide IV over 30 minutes on day 1 every 3 weeks for a total of 4 courses. After completion of course 4, patients receive paclitaxel IV and trastuzumab IV over 90 minutes weekly on weeks 13-24. Patients then may undergo radiotherapy followed by trastuzumab IV over 30 minutes weekly on weeks 29-69 if they did not receive radiotherapy or on weeks 36-76 if they did receive radiotherapy.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 125 patients (100 in the neoadjuvant group and 25 in the adjuvant group) will be accrued for this study within 5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 85
• Est. completion date: April 2013
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed stage IIB, IIIA, IIIB, IIIC, or previously untreated stage IV primary carcinoma of the breast

• Fine needle aspiration, core needle biopsy, or incisional biopsy allowed

• No excisional biopsy

• Any of the following:

• T2, N1 or T3, N0

• Any T with N2 (including axillary lymph nodes matted to one another) or N3

• Any T4, including inflammatory breast cancer

• Adjuvant patients with at least 4 positive lymph nodes and HER-2 overexpressing tumor

• Supraclavicular or infraclavicular positive lymph nodes without distant metastases

• Distant metastases with measurable disease in breast or lymph nodes

• Synchronous bilateral primary breast cancer allowed if the more serious cancer meets entry criteria

• Measurable or evaluable disease

• Hormone receptor status:

• Not specified

PATIENT CHARACTERISTICS:

Age:

• Not specified

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• WBC greater than 3,000/mm^3

• Platelet count greater than 100,000/mm^3

• Hemoglobin greater than 9 g/dL

Hepatic:

• Bilirubin less than 1.5 times normal

Renal:

• Creatinine less than 1.5 times normal

Cardiovascular:

• LVEF normal by resting nuclear ventriculogram

Other:

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No other prior malignancies except:

• Effectively treated squamous cell or basal cell skin cancer

• Carcinoma in situ of the cervix that has been curatively treated by surgery alone

• Nonbreast malignancy from which patient has been disease-free for 5 years and is at low risk of recurrence

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• Not specified

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• trastuzumab
infusion 4 mg/kg load week 1; 2 mg/kg weekly thereafter for 12 weeks

Drug:
• cyclophosphamide
600 mg/m2, intravenous infusion every 3 weeks for four cycles
• doxorubicin hydrochloride
60 mg/m2 intravenously, 5-10 minutes, every 3 weeks, up to 12 weeks
• paclitaxel
90 mg/m2 weekly, intravenously 1 hour after herceptin, given weekly up to 12 weeks or 175 mg/m2, intravenously every 3 weeks, up to 12 weeks (only if not receiving Herceptin®)

Procedure:
• conventional surgery
Surgical excision will take place 12-13 weeks for the neo-adjuvant herceptin setting and 12-13 weeks in the non-herceptin setting. Surgery will take place prior to chemotherapy in the adjuvant herceptin setting

Radiation:
• Radiation Therapy
All patients undergoing breast-conserving surgery will undergo adjuvant (after surgery) whole breast radiation therapy. If the patient undergoes mastectomy, postmastectomy radiotherapy to the chest wall, supraclavicular region and axilla will be administered at the discretion of the treating radiation oncologist

Locations

Country	Name	City	State
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
UNC Lineberger Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the cardiac and other toxicity of weekly Taxol given with weekly Herceptin when delivered immediately following four cycles of standard dose AC		15 weeks from start of treatment	Yes
Secondary	To identify whether the addition of Taxol® with or without Herceptin® further decreases tumor size and the number of positive axillary lymph nodes beyond that achieved by conventional breast cancer adjuvant therapy (4AC).		Six-and-one-half years from start of treatment	No
Secondary	To determine the 10 year DFS and OS in patients receiving and not receiving Herceptin®, and determine whether the initial pathologic response in Neoadjuvant patients correlates with the eventual 5-year DFS or OS		10 years from date of last treatment	No