Clinical trial NCT00647218: Paclitaxel and Radiation Therapy in Treating Patients Undergoing Surgery for Stage II or Stage III Breast Cancer
Official title: A Pilot Study of Neoadjuvant Paclitaxel and Concurrent Radiation With Correlative Molecular Studies in Stage II/III Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Cancer
Keywords: stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-03-31
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving paclitaxel and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This clinical trial is studying how well giving paclitaxel together with radiation therapy works in treating patients undergoing surgery for stage II or stage III breast cancer.

Detailed description: OBJECTIVES:

Primary

* Evaluate the efficacy of paclitaxel and concurrent radiotherapy (as measured by pathologic response rates) in patients with stage II or III breast cancer.

Secondary

* Evaluate the toxicities of this treatment regimen.
* Correlate paclitaxel-induced tumor response with local recurrence-free survival, distant disease-free survival, and overall survival.
* Evaluate protein expression profiles by mass spectrometry in biopsy material and blood specimens collected before and after treatment with paclitaxel.

OUTLINE:

* Neoadjuvant chemotherapy: Patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.
* Chemoradiotherapy: Beginning 3-4 weeks after completion of neoadjuvant chemotherapy, patients receive paclitaxel IV over 1 hour twice weekly and undergo radiotherapy once daily, 5 days a week, for 6½ weeks.
* Surgery: At 6-8 weeks after completion of chemoradiotherapy, patients undergo surgical resection (e.g., modified radical mastectomy or lumpectomy and axillary node dissection).
* Adjuvant chemotherapy: Beginning 4-6 weeks after surgery, patients receive doxorubicin hydrochloride IV over 20 minutes and cyclophosphamide IV over 1 hour on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
* Hormonal therapy: After completion of adjuvant chemotherapy, patients with estrogen receptor- and/or progesterone receptor-positive tumor receive hormonal therapy at the discretion of the treating physician.

Patients undergo blood and tissue sample collection periodically to analyze changes in cell cycle by flow cytometry; antibody assays; kinase assays for cyclin B1/CDC2; genetic assays for p53, p21, and other molecular markers; and protein expression assays by mass spectrometry.

After completion of study therapy, patients are followed periodically.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically documented invasive carcinoma of the breast\*

  * Tumor ≥ 2 cm in greatest dimension (e.g., T2-4) and any nodal status (e.g., N0-3), including locally advanced disease, as defined by the following criteria:

    * Primary tumor ≥ 5 cm
    * Tumor of any size with direct extension to the chest wall or skin
    * Inflammatory breast cancer (T4d)
    * Metastasis to ipsilateral internal mammary node
    * Ipsilateral lymph nodes that are clinically fixed to each other or to other structures (N2) NOTE: \*Diagnosis may be made by core or tru-cut biopsies
* Measurable or evaluable tumor

  * Measurable disease is defined as any mass that can be reproducibly measured in two perpendicular dimensions
  * Evaluable disease is defined as any lesion visible by mammogram or palpable by physical exam that does not fit the above criteria of measurability
* Planning to undergo breast conservation surgery
* Willing to undergo AND is a candidate for radiotherapy, in the judgement of the treating radiation oncologist
* No evidence of distant metastatic disease (e.g., lung, liver, bone, brain)
* Hormone receptor status not specified

PATIENT CHARACTERISTICS:

* Menopausal status not specified
* ECOG performance status 0-1
* WBC ≥ 3,000/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Creatinine ≤ 1.5 times upper limit of normal (ULN)
* Bilirubin ≤ 1.5 times ULN
* Left ventricular ejection fraction ≥ 45%
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No other malignancies within the past 5 years, except curatively treated nonmelanomatous skin cancer or carcinoma in situ of the cervix
* No history of hypersensitivity reaction to products containing polysorbate 80 (Tween 80)
* No serious medical illness that, in the judgment of the treating physician, places the patient at risk
* No peripheral neuropathy ≥ grade 2

PRIOR CONCURRENT THERAPY:

* Prior tamoxifen as chemoprevention allowed
* No prior radiotherapy to the ipsilateral breast

  * Prior radiotherapy to the contralateral breast is allowed
* No prior chemotherapy

Primary outcomes:
measure: Pathologic Complete Response Rate
timeFrame: 9 weeks
Secondary outcomes:
measure: Toxicity paclitaxel and radiation
timeFrame: at 18 weeks
measure: Correlation of tumor response with local recurrence-free survival, distant disease-free survival, and overall survival
timeFrame: at time of disease progression or death by any cause
measure: Protein expression profiles as measured by mass spectrometry before and after treatment with paclitaxel
timeFrame: Baseline and 18 weeks
Other outcomes:
Locations:
city: Frankling
country: United States
facility: Williamson Medical Center
state: Tennessee
city: Jackson
country: United States
facility: Jackson-Madison Hospital
state: Tennessee
city: Memphis
country: United States
facility: Boston Baskin Cancer Center
state: Tennessee
city: Memphis
country: United States
facility: Methodist Lebonheur Healthcare
state: Tennessee
city: Nashville
country: United States
facility: Meharry Medical College
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Cetner
state: Tennessee
Study officials:
affiliation: Vanderbilt-Ingram Cancer Center
name: A. Bapsi Chakravarthy, MD
role: STUDY_CHAIR
References: