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

NCT ID: NCT00006110

Last Updated: 2017-07-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-12-31
• Study Completion Date: 2013-04-30

Brief 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.

Detailed 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 either received neoadjuvant therapy (HER-2 overexpressing and non-overexpressing patients) or adjuvant therapy (HER-2 overexpressing patients only).

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

• Regimen I (HER-2 non-overexpressing 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 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.

Conditions

Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neo-adjuvant Herceptin with or without radiation

Chemotherapy followed by Taxol plus Herceptin followed by surgery followed by radiation (or no radiation) followed by additional Herceptin

Group Type: EXPERIMENTAL

trastuzumab

Intervention Type: BIOLOGICAL

infusion 4 mg/kg load week 1; 2 mg/kg weekly thereafter for 12 weeks

cyclophosphamide

Intervention Type: DRUG

600 mg/m2, intravenous infusion every 3 weeks for four cycles

doxorubicin hydrochloride

Intervention Type: DRUG

60 mg/m2 intravenously, 5-10 minutes, every 3 weeks, up to 12 weeks

paclitaxel

Intervention Type: DRUG

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®)

conventional surgery

Intervention Type: PROCEDURE

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

Non-Herceptin with or without radiation

Chemotherapy followed by Taxol followed by surgery followed by radiation (or no radiation)

Group Type: EXPERIMENTAL

cyclophosphamide

Intervention Type: DRUG

600 mg/m2, intravenous infusion every 3 weeks for four cycles

doxorubicin hydrochloride

Intervention Type: DRUG

60 mg/m2 intravenously, 5-10 minutes, every 3 weeks, up to 12 weeks

paclitaxel

Intervention Type: DRUG

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®)

conventional surgery

Intervention Type: PROCEDURE

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

Interventions

trastuzumab

infusion 4 mg/kg load week 1; 2 mg/kg weekly thereafter for 12 weeks

Intervention Type: BIOLOGICAL

cyclophosphamide

600 mg/m2, intravenous infusion every 3 weeks for four cycles

Intervention Type: DRUG

doxorubicin hydrochloride

60 mg/m2 intravenously, 5-10 minutes, every 3 weeks, up to 12 weeks

Intervention Type: DRUG

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®)

Intervention Type: DRUG

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

Intervention Type: PROCEDURE

Other Intervention Names

Herceptin; Lyophilized Cytoxan; Endoxan; Cytoxan; Neosar; Procytox; Revimmune; Cycloblastin; Adriamycin; Taxol

Eligibility Criteria

Inclusion Criteria

• 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:

• Tumor size 2, Nodes 1 (T2N1) or tumor size 3 nodes 0 (T3N0)
• 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

PATIENT CHARACTERISTICS:

Age: Not specified

Sex: Female

Menopausal status: Not specified

Performance status: Not specified

Life expectancy: Not specified

Hematopoietic:

White cell count > 3000 / mm3 Platelet count > 100,000 / mm3

Hemoglobin > 9 mg / dl Bilirubin < 1.5 x normal Creatinine < 1.5 x normal left ventricular ejection fraction (LVEF) normal by resting nuclear ventriculogram Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception

Exclusions

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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 120 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lisa A. Carey, MD

Role: STUDY_CHAIR

UNC Lineberger Comprehensive Cancer Center

Locations

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, United States

Countries

United States

Related Links

http://grantome.com/grant/NIH/M01-RR000046-44-1159

Clinical trial summary from the NIH

http://dx.doi.org/10.3816/CBC.2006.n.035

results published in Clinical Breast Cancer

Other Identifiers

LCCC9818

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-G00-1836

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

LCCC 9818

Identifier Type: -

Identifier Source: org_study_id