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Neoadjuvant Chemotherapy Using Doxorubicin and Paclitaxel in Treating Women With Large Breast Cancer

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.
 
ClinicalTrials.gov Identifier: NCT00096291
Recruitment Status : Completed
First Posted : November 9, 2004
Last Update Posted : April 10, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alphonse Taghian, MD, PhD, Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE November 9, 2004
First Posted Date  ICMJE November 9, 2004
Last Update Posted Date April 10, 2017
Study Start Date  ICMJE February 2000
Actual Primary Completion Date March 2005   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 7, 2012)
•Determine whether tumors in women with palpable invasive breast cancer with wild type p53 are more sensitive to doxorubicin than to paclitaxel when given as sequential single-agent neoadjuvant chemotherapy [ Time Frame: asses pathological response to neoadjuvant chemotherapy ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neoadjuvant Chemotherapy Using Doxorubicin and Paclitaxel in Treating Women With Large Breast Cancer
Official Title  ICMJE Neoadjuvant Chemotherapy in Palpable Breast Cancer: Evaluation of Physiologic, Radiologic, and Molecular Markers in Predicting Response
Brief Summary

RATIONALE: Drugs used in chemotherapy, such as doxorubicin and paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving chemotherapy before and after surgery may shrink the tumor so it can be removed and may kill any tumor cells remaining after surgery.

PURPOSE: This randomized phase II trial is comparing two different regimens of doxorubicin and paclitaxel to see how well they work in treating women who are undergoing surgery for breast cancer.

Detailed Description

OBJECTIVES:

Primary

  • Determine whether tumors in women with palpable invasive breast cancer with wild type p53 are more sensitive to doxorubicin than to paclitaxel when given as sequential single-agent neoadjuvant chemotherapy.
  • Determine whether tumors with inactivated p53 are more sensitive to paclitaxel than to doxorubicin when given as sequential single-agent neoadjuvant chemotherapy in these patients.

Secondary

  • Correlate other biological markers (physiological and molecular) with tumor response in patients treated with these regimens.
  • Determine changes in these biological markers during and after neoadjuvant chemotherapy in these patients.
  • Compare breast MRI, in terms of assessing tumor response, with physical exam, mammogram, and ultrasound in patients treated with these regimens.
  • Determine whether there are MRI indicators (e.g., tumor morphology or lesion enhancement) that are predictive of response in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to tumor size (> 5 cm vs ≤ 3-5 cm) and presence of palpable regional lymph nodes (yes vs no). Patients are randomized to 1 of 2 treatment arms.

All patients undergo biopsy, bilateral mammogram, MRI, ultrasound, blood marker, molecular (gene microarrays and functional p53 status), and physiologic studies before initiation of neoadjuvant chemotherapy. Some of these studies are repeated after completion of treatment with the first chemotherapeutic agent and after completion of treatment with the second chemotherapeutic agent as outlined below.

  • Arm I: Patients receive doxorubicin IV on days 1, 15, 29, and 43. Patients with no residual tumor (indicated by clinical evaluation and radiologic studies) after completion of doxorubicin undergo definitive surgery. After surgery, patients receive paclitaxel IV over 1 hour on days 1, 8, 15, 22, 29, 36, 43, 50, and 57.

Patients with residual tumor > 2 cm after completion of doxorubicin undergo 8-12 core needle biopsies. Patients with residual tumor < 2 cm after completion of doxorubicin undergo 4-6 core needle biopsies. After core needle biopsies, patients receive paclitaxel as above.

  • Arm II: Patients receive paclitaxel IV over 1 hour on days 1, 8, 15, 22, 29, 36, 43, 50, and 57. Patients with no residual tumor (indicated by clinical evaluation and radiologic studies) after completion of paclitaxel undergo definitive surgery. After surgery, patients receive doxorubicin IV on days 1, 15, 29, and 43.

Patients with residual tumor > 2 cm after completion of paclitaxel undergo 8-12 core needle biopsies. Patients with residual tumor < 2 cm after completion of paclitaxel undergo 4-6 core needle biopsies. After core needle biopsies, patients receive doxorubicin as above.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Samples from core needle biopsies are analyzed by microarray analysis for gene expression profiles.

Patients are followed every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this study within 4-5 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Other: Doxorubicin followed by Paclitaxel

    Patients will be randomized into 2 groups based on sequence of neoadjuvant chemotherapy:

    Doxorubicin followed by Paclitaxel Paclitaxel followed by Doxorubicin

  • Other: Paclitaxel followed by Doxorubicin

    Patients will be randomized into 2 groups based on sequence of neoadjuvant chemotherapy:

    Doxorubicin followed by Paclitaxel versus Paclitaxel followed by Doxorubicin

Study Arms  ICMJE
  • Active Comparator: Sequence Doxorubicin followed by Paclitaxel

    Patients will be randomized into 2 groups based on sequence of neoadjuvant chemotherapy:

    Doxorubicin followed by Paclitaxel versus Paclitaxel followed by Doxorubicin

    Interventions:
    • Other: Doxorubicin followed by Paclitaxel
    • Other: Paclitaxel followed by Doxorubicin
  • Sequence of neoadjuvant CT: Paclitaxel followed by Doxorubicin

    Patients will be randomized into 2 groups based on sequence of neoadjuvant chemotherapy:

    Doxorubicin followed by Paclitaxel versus Paclitaxel followed by Doxorubicin

    Intervention: Other: Paclitaxel followed by Doxorubicin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 7, 2012)
62
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date March 2005   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Diagnosis of invasive breast cancer

    • Tumor ≥ 3 cm and palpable

      • Multiple masses are allowed provided at least 1 mass is ≥ 3 cm
    • Clinically positive axillary or supraclavicular lymph nodes allowed
    • Fine needle aspiration or core needle biopsy positive for invasive breast cancer AND/OR fine needle aspiration of lymph nodes positive
  • HER2/neu-positive OR negative
  • No inflammatory breast cancer
  • No distant metastases
  • Hormone receptor status:

    • Estrogen receptor (ER)-positive OR ER-negative

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Sex

  • Female

Menopausal status

  • Premenopausal or postmenopausal

Performance status

  • Karnofsky 60-100%

Life expectancy

  • Not specified

Hematopoietic

  • Granulocyte count ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3

Hepatic

  • Bilirubin ≤ 2 times upper limit of normal (ULN)
  • SGOT ≤ 2 times ULN

Renal

  • Not specified

Cardiovascular

  • LVEF ≥ 50%
  • No congestive heart failure
  • No serious conduction system abnormality
  • No other significant cardiovascular disease

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Patients with other prior or concurrent malignancies allowed provided they have received no prior chemotherapy AND they are likely to have been cured from a prior malignancy
  • No severe medical or psychiatric condition that would preclude study compliance
  • No known HIV positivity

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior chemotherapy

Endocrine therapy

  • No prior hormonal therapy for breast cancer

Radiotherapy

  • No prior radiotherapy for this malignancy

Surgery

  • Not specified
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00096291
Other Study ID Numbers  ICMJE CDR0000382123
P50CA089393 ( U.S. NIH Grant/Contract )
P30CA006516 ( U.S. NIH Grant/Contract )
DFCI-99278
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alphonse Taghian, MD, PhD, Massachusetts General Hospital
Study Sponsor  ICMJE Massachusetts General Hospital
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Alphonse G. Taghian, MD, PhD Dana-Farber Cancer Institute
PRS Account Massachusetts General Hospital
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP