Docetaxel Followed by Surgery in Treating Women With Stage II or Stage III Breast Cancer

This study has been terminated.
(closed due to competing neoadjuvant studies for a small patient population)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Bapsi Chak, MD, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier:
NCT00343512
First received: June 22, 2006
Last updated: April 21, 2012
Last verified: April 2012
  Purpose

RATIONALE: Dose-dense scheduling with (peg)filgrastim support may improve the clinical and pathologic complete response rate (pCR) and safety profile of single agent neoadjuvant docetaxel therapy.

PURPOSE: To evaluate whether dose-dense scheduling with (peg)filgrastim support may improve the clinical and pathologic complete response rate (pCR) and safety profile of single agent neoadjuvant docetaxel therapy. To determine the changes in molecular markers that occurs with single agent docetaxel, tissue will be obtained at the end of the four cycles of docetaxel (either by repeat biopsy or definitive surgery).


Condition Intervention Phase
Breast Cancer
Drug: docetaxel
Genetic: protein expression analysis
Other: laboratory biomarker analysis
Procedure: biopsy
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of Neoadjuvant Dose Dense Docetaxel With Correlative Molecular Studies in Stage II/III Breast Cancer

Resource links provided by NLM:


Further study details as provided by Vanderbilt-Ingram Cancer Center:

Primary Outcome Measures:
  • Number Participants to Achieve Pathologic Complete Response [ Time Frame: 3 month ] [ Designated as safety issue: No ]
    whether or not patient has pathologic complete response (pCR) to dose dense docetaxel in the neoadjuvant setting (pCR = no residual viable tumor on histologic analysis)


Secondary Outcome Measures:
  • Safety Profile Based on Number of Patients With Each Worst-grade Toxicity [ Time Frame: Through 30 days after completion of treatment ] [ Designated as safety issue: Yes ]
    Not all participants necessarily have an adverse event, thus not everyone will be accounted for in worst-grade toxicities. Likewise, one participant can potentially have more than one event in various grades 1-5 which accounts for the difference in number of patients analyzed and total number in the worst-grade toxicity tables. Tables represent the number of patients with worst-grade toxicity at each of five grades (grade 1, least severe; to grade 5, most severe) following NCI Common Toxicity Criteria

  • Tumor Response as Measured by Ultrasound [ Time Frame: At screening, 8 weeks and at surgery (within 14-21 days) ] [ Designated as safety issue: No ]
    Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.


Enrollment: 34
Study Start Date: February 2004
Study Completion Date: March 2011
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Therapeutic Intervention Drug: docetaxel
Docetaxel 75 mg/m2 IV (1-hour infusion) on day 1 of each cycle (cycle = 2 weeks) x 4 cycles
Other Name: Taxotere
Genetic: protein expression analysis
protein expression analysis
Other Name: protein expression analysis
Other: laboratory biomarker analysis
laboratory biomarker analysis
Other Name: laboratory biomarker analysis
Procedure: biopsy
biopsy
Other Name: biopsy
Procedure: conventional surgery
conventional surgery
Other Name: conventional surgery
Procedure: neoadjuvant therapy
neoadjuvant therapy
Other Name: neoadjuvant therapy

Detailed Description:

OBJECTIVES:

Primary

  • Pathologic complete response rate (pCR) of dose dense docetaxel in the neoadjuvant setting.

Secondary

  • Safety and toxic effects of this regimen in these patients.
  • Tumor response rate (as measured by ultrasound) in patients treated with this regimen.
  • Determine whether early changes in markers of cell cycle position, proliferation, or apoptosis correlate with pathologic complete response rate in these patients.
  • Determine whether the molecular profile that predicts for chemoresponsiveness also predicts for response to radiotherapy (as measured by local recurrence) in these patients.
  • Determine whether tumors that demonstrate the greatest degree of change in protein expression patterns from pre- to post-docetaxel treatment will also be those that are most sensitive to chemotherapy (as measured by pathologic response rate) in these patients.

OUTLINE: This is a nonrandomized, open-label, pilot study.

  • Tissue Collection: Patients undergo tumor core biopsy (6-8 cores) and blood collection prior to initiating neoadjuvant docetaxel.
  • Neoadjuvant docetaxel with hematopoietic support: Patients receive docetaxel IV over 1 hour on day 1. Patients also receive pegfilgrastim subcutaneously (SC) on day 1 or 2 of each course OR filgrastim (G-CSF) or sargramostim (GM-CSF) SC daily beginning between day 2-4 of each course and continuing until blood counts recover. Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
  • Surgery: Within 4-6 weeks after completion of neoadjuvant docetaxel, patients undergo definitive surgery.

Patients undergo tumor biopsy and blood collection periodically for pharmacokinetic, genetic, and molecular biomarker correlative studies. Samples are examined for changes in p21 protein expression (and/or p21 phosphorylation) and the protein expression profile.

After completion of study treatment, patients are followed at least every 6 months for 3 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

Inclusion:

  • Histologically or cytologically confirmed invasive carcinoma of the breast by core biopsy
  • Tumor ≥ 2 cm in greatest dimension(may be either node positive or node negative disease
  • Patients with non-metastatic breast cancer who are in the judgment of the treating medical oncologist considered to be of sufficiently high risk to warrant adjuvant chemotherapy

    • Patients with internal mammary, supraclavicular and/or axillary node involvement are eligible. Patients with inflammatory breast cancer are eligible
    • Patients with T0 disease but palpable and measurable adenopathy are eligible for this trial. All sites of disease should be noted and followed
  • Hormone receptor status:

    • Not specified

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Menopausal status not specified
  • Female ≥ 18 years old
  • Absolute neutrophil count ≥ 1,000/mm^3
  • Hemoglobin ≥ 8 g/dL
  • Platelet count ≥ 100,000/mm^3
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)
  • Bilirubin normal
  • Alkaline phosphatase (AP), AST, and ALT meeting 1 of the following criteria:

    • AP normal AND AST or ALT ≤ 5 times ULN
    • AP ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN
    • AP ≤ 5 times ULN AND AST or ALT normal
  • Women of child-bearing potential, must have a negative serum pregnancy test and must use effective contraception for the duration of the study and for at least 6 months after completion of study treatment
  • Patients with prior malignancies are eligible if they have been disease free for ≥ 5 years. Patients with curative treatment of non-melanomatous skin cancer, carcinoma in situ of the cervix, contralateral DCIS treated with mastectomy are eligible even if it is diagnosed in < 5 years.

PRIOR CONCURRENT THERAPY:

  • No prior anthracycline or taxane-based chemotherapy. Patients who received chemoprevention are eligible if the chemopreventive agent has been discontinued for at least one year prior to enrollment in the current study.
  • At least 1 year since prior tamoxifen for breast cancer prevention

Exclusion:

  • Prior radiotherapy to the ipsilateral breast

    • Patients who have had radiation to the contralateral breast are eligible
  • Evidence of distant metastatic disease (i.e., lung, liver, bone, brain)
  • Pregnant of breastfeeding
  • Patients who have congestive heart failure, angina pectoris, uncontrolled cardiac arrhythmia, or other significant heart disease, or who have had a myocardial infarction within the past year
  • Patients with > grade 1 peripheral neuropathy
  • Patients with a history of hypersensitivity reaction to products containing polysorbate 80 (Tween 80)
  • Patients receiving an investigational anticancer drug within 3 weeks of registration
  • Patients with serious medical illness that in the judgment of the treating physician, places the patient at risk.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00343512

Locations
United States, Tennessee
Meharry Medical College
Nashville, Tennessee, United States, 37208
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
Investigators
Principal Investigator: A. Bapsi Chakravarthy, MD Vanderbilt-Ingram Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Bapsi Chak, MD, Associate Professor; Radiation Oncologist, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier: NCT00343512     History of Changes
Other Study ID Numbers: VICC BRE 0368, VICC-BRE-0368, VICC-11239
Study First Received: June 22, 2006
Results First Received: October 11, 2010
Last Updated: April 21, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanderbilt-Ingram Cancer Center:
inflammatory breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Docetaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 16, 2014