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

Phase 2

Terminated

• Conditions: Breast Cancer
• Interventions: Drug: docetaxel; Genetic: protein expression analysis; Other: laboratory biomarker analysis; Procedure: biopsy; Procedure: conventional surgery; Procedure: neoadjuvant therapy

• Registration Number: NCT00343512
• Lead Sponsor: Vanderbilt-Ingram Cancer Center

Brief Summary

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).

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.

Study Timeline

• Study Start: 2004-02
• Study First Submitted: 2006-06-22
• Study First Submitted QC: 2006-06-22
• Study First Posted: 2006-06-23
• Primary Completion: 2008-03
• Results First Submitted: 2010-10-11
• Results First Submitted QC: 2010-10-11
• Results First Posted: 2010-11-09
• Study Completion: 2011-03
• Status Verified: 2012-04
• Last Update Submitted: 2012-04-21
• Last Update Posted: 2012-04-27

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 34

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Therapeutic Intervention	conventional surgery	-
Therapeutic Intervention	laboratory biomarker analysis	-
Therapeutic Intervention	neoadjuvant therapy	-
Therapeutic Intervention	protein expression analysis	-
Therapeutic Intervention	biopsy	-
Therapeutic Intervention	docetaxel	-

Primary Outcome Measures

Name	Time	Method
Number Participants to Achieve Pathologic Complete Response	3 month	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

Name	Time	Method
Safety Profile Based on Number of Patients With Each Worst-grade Toxicity	Through 30 days after completion of treatment	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	At screening, 8 weeks and at surgery (within 14-21 days)	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.

Trial Locations

Locations (2)

Meharry Medical College; 🇺🇸 Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center; 🇺🇸 Nashville, Tennessee, United States