Study of Concurrent Paclitaxel and Radiation: Correlation of Tumor Profiles With Pathologic Response

Study Overview
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Brief Summary
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The need to understand LABC is especially compelling in populations and countries with limited resources, where breast cancer incidence is relatively low, but mortality is comparably high. In these settings access to appropriate cancer care is characteristically limited or often plainly nonexistent. In contrast to economically developed nations, where on average fewer than 20% of women present with breast cancer at advanced stages, LABC and metastatic disease are the most common stages at presentation in 50% or more women in Latin America, Asia and Africa.

Detailed Description
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The term -locally advanced breast cancer (LABC) commonly includes tumors whose maximum diameter is 5 cm (T3) or larger, or which present with involvement of the chest wall or skin. Surprisingly, the simultaneous presence of clinically detectable distant metastases is relatively infrequent ( 8%), a peculiar finding since in 73% of these large tumors it is possible to document shedding of tumor cells into the blood. While LABC has become a rare clinical presentation of breast cancer in the general population as a result of improved early detection by mammographic screening, it remains relatively common among minority women of low socioeconomic status. For instance, in a consecutive series of 363 African-American women presenting in a large urban hospital, one out of three women newly diagnosed with breast cancer had LABC. It is well documented that although the incidence of breast cancer among African-Americans is lower than among white women, breast cancer mortality in African-Americans is significantly higher. In 1998, the American Cancer Society, the National Cancer Institute and the Centers for Disease Control and Prevention reported an overall downward trend in cancer incidence and mortality between 1990 and 1995 for all cancers combined. Many minority and medically underserved populations, however, did not share equally in these improvements. These patients have continued to encounter multifactorial barriers to early detection and care, warranting interventions to improve access. At the same time, it is equally important to offer the best chance for survival to those underserved women who have already availed themselves of medical care. Paradoxically, while the medical community is aware of the inadequate accrual of minority patients to clinical trials, only few trials exist for LABC.

Official Title
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Response, Resistance and Metastasis of Locally Advanced Breast Cancer (LABC, Stage 2B-3C) in a Multiethnic Cohort: A Phase II International Multicentric Study of Concurrent Paclitaxel and Radiation

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Paclitaxel
* Radiation: Radiation therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy proven locally-advanced breast cancer: IIB, IIIA, and IIIB Metastatic breast cancer: limited to the subset of patients with intact breast, locally advanced tumor and involved ipsilateral supraclavicular nodes Measureable disease required Adequate laboratory values: Hgb > 10 ANC > 1500 Platelets > 150,000 Creatinine < 1.5 Liver function < 3x normal Patient ≥ 18 years of age Medically and psychologically able to comply with all study requirements ECOG performance score 0-1 CT chest, abdomen, and pelvis performed Mammogram or USG performed Signed informed consent Exclusion Criteria: Breast cancer patients with Stage 0, Stage I, or Stage IIA Previous XRT or chemotherapy Presence of distant metastases documented clinically or radiographically with the exception of ipsilateral supraclavicular nodes Pregnancy Inflammatory breast cancer Patients under treatment (or who will have recently been treated) with anti-neoplastic, immunosuppressive or hormonal medications Patients who are found to have a cancer positive for the marker HER-2/neu (applies only to NYU Tisch and Bellevue sites)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Concurrent Paclitaxel and RT<br>Patients will be administered pre-operatively over 12 weeks either: Paclitaxel, 30mg/m^2 twice per week, intravenously over 1 hour on a Monday/Thursday or Tuesday/Friday schedule Abraxane, 30mg/m^2 twice per week, intravenously administered over 30 minutes, on a Monday/Thursday or Tuesday/Friday schedule Patients will concurrently receive 6 weeks of radiation therapy, weeks 2-7: Patients will receive a total dose to the breast, axilla and supraclavicular area of 45 Gy at 1.8 Gy/fraction, +14 Gy to the area of the original palpable tumor at 2 Gy/fraction (32 fractions) | Drug: Paclitaxel<br>* Paclitaxel (including Abraxane), 30 mg/m2 twice per week. Paclitaxel will be given IV over 1 hour, Abraxane® will be administered over 30 min, and administered on a Monday/Thursday or Tuesday/Friday schedule.<br>* Other names: Abraxane;Radiation: Radiation therapy<br>* Patients will receive a total dose of 45 Gy to the breast, axilla and supraclavicular area at 1.8 Gy/fraction, +14 Gy to the original palpable tumor at 2 Gy/fraction (total 32 fractions)<br>* Other names: radiotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Test the Clinical Effectiveness of Concurrent Paclitaxel and Radiation in a Multiethnic Cohort | Test the effectiveness of concurrent paclitaxel and radiation in a prospective multiethnic cohort of patients with newly diagnosed stage 2B-3C breast cancer treated at three international academic centers under uniform conditions. Local recurrence, regional recurrence and overall survival will be measured | 4.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure the Pathological Response Rate of Concurrent Paclitaxel-radiation | Measure the pathological response rate to concurrent paclitaxel-radiation at each collaborating institution and compare it to that achieved in a previous Phase I-II trial | 4.5 years | 
| Perform Molecular Biology and Genomic Studies of Obtained Core Biopsies to Identify Biomarkers for Predisposition to Breast Cancer | Obtain core biopsies of the original tumor before and after treatment (from the surgical specimen) for molecular biology and genomic studies of biomarkers and genetic anomalies that may signal a population's predisposition to breast cancer and/or susceptibility to study intervention | 4.5 years | 
| Patient Demographics | Acquire descriptive information on patient epidemiological, cultural and behavioral characteristics | 4.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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paclitaxel, Locally-advanced Breast Cancer, LABC, breast cancer, breast, cancer, metastasis, metastatic, tumor, radiation, radiation therapy, radiotherapy