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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00006110
First Posted: January 27, 2003
Last Update Posted: July 31, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
  Purpose

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.


Condition Intervention Phase
Breast Cancer Biological: trastuzumab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: paclitaxel Procedure: conventional surgery Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Nonrandomized Ph II Study of Multimodality Therapy for Stg IIB, IIIA/B, or Stg IV Breast Cancer w/4 Cycles of Adriamycin and Cytoxan (AC),Followed by 12 Weeks of Paclitaxel w/ or w/o Herceptin Followed by Local Therapy Followed by Wkly Herceptin or no Additional Therapy

Resource links provided by NLM:


Further study details as provided by UNC Lineberger Comprehensive Cancer Center:

Primary Outcome Measures:
  • Cardiac Toxicity of Weekly Taxol Given With Weekly Herceptin When Delivered Immediately Following Four Cycles of Standard Dose AC. [ Time Frame: 78 weeks (1.5 years) ]
    Doxorubicin + cyclophosphamide in combination with paclitaxel and trastuzumab (AC-TP) Associated Systolic Dysfunction. Systolic function was measured by the ventricular ejection fraction (LVEF). LVEF is a measurement in determining how well your heart is pumping out blood and in diagnosing and tracking heart failure.


Secondary Outcome Measures:
  • Overall Response [ Time Frame: 78 weeks (1.5 years) ]
    Measured by the Overall Response. Response: Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  • Disease-free Survival (DFS) in Patients Receiving and Not Receiving Herceptin®. [ Time Frame: 5 years ]
    Percent of patients receiving and not receiving Herceptin who are alive and disease-free at 5 years.


Enrollment: 82
Study Start Date: December 1998
Study Completion Date: April 2013
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Biological: trastuzumab
infusion 4 mg/kg load week 1; 2 mg/kg weekly thereafter for 12 weeks
Other Name: Herceptin
Drug: cyclophosphamide
600 mg/m2, intravenous infusion every 3 weeks for four cycles
Other Names:
  • Lyophilized Cytoxan
  • Endoxan
  • Cytoxan
  • Neosar
  • Procytox
  • Revimmune
  • Cycloblastin
Drug: doxorubicin hydrochloride
60 mg/m2 intravenously, 5-10 minutes, every 3 weeks, up to 12 weeks
Other Name: Adriamycin
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®)
Other Name: Taxol
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
Experimental: Non-Herceptin with or without radiation
Chemotherapy followed by Taxol followed by surgery followed by radiation (or no radiation)
Drug: cyclophosphamide
600 mg/m2, intravenous infusion every 3 weeks for four cycles
Other Names:
  • Lyophilized Cytoxan
  • Endoxan
  • Cytoxan
  • Neosar
  • Procytox
  • Revimmune
  • Cycloblastin
Drug: doxorubicin hydrochloride
60 mg/m2 intravenously, 5-10 minutes, every 3 weeks, up to 12 weeks
Other Name: Adriamycin
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®)
Other Name: Taxol
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

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 120 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00006110


Locations
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7305
Comprehensive Cancer Center at Wake Forest University
Winston-Salem, North Carolina, United States, 27157-1082
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Investigators
Study Chair: Lisa A. Carey, MD UNC Lineberger Comprehensive Cancer Center
  More Information

Additional Information:
Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00006110     History of Changes
Other Study ID Numbers: LCCC 9818
LCCC9818 ( Other Identifier: UNC Lineberger Comprehensive Cancer Center )
NCI-G00-1836 ( Other Grant/Funding Number: NCI )
First Submitted: August 3, 2000
First Posted: January 27, 2003
Results First Submitted: April 5, 2017
Results First Posted: July 31, 2017
Last Update Posted: July 31, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
stage II breast cancer
stage IV breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
inflammatory breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Liposomal doxorubicin
Albumin-Bound Paclitaxel
Cyclophosphamide
Doxorubicin
Trastuzumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors