Gemcitabine, Doxorubicin and Paclitaxel (GAT) as Neoadjuvant Treatment of Breast Cancer Patients

Study Overview
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Brief Summary
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This is a multicenter, open-label, phase II trial to assess the efficacy of the GAT neoadjuvant regimen in patients with stage III breast cancer.

Detailed Description
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2 treatment cycles of chemotherapy (one cycle = 2 weeks) must be administered to each patient before breast surgery. The required number of patients has been calculated following Simon's method. 43 patients will be enrolled in two phases: first, 29 patients must be enrolled, and at least 2 pathological complete responses obtained. Patients recruitment will continue until 43 patients have been enrolled. Assumptions are that there is a 95% probability to obtain a rate of pathological complete responses of at least 10%.

Official Title
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Phase II Pharmacogenomic and Clinical Trial for the Administration of Gemcitabine-doxorubicin-paclitaxel (GAT) as Neoadjuvant Treatment of Patients With Stage III Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Gemcitabine
* Drug: Adriamycine
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage III breast cancer disease, with histological confirmation by true-cut or open-biopsy. Ages between 18 and 75 years old. Patients older than 70 must have an adequate quality of life to be eligible. Patients cannot have received previous treatment with chemotherapy, hormone therapy, radiotherapy or immune therapy. Performance status of 0,1, 2 Eastern Cooperative Oncology Group (ECOG). At least a 6 month life expectancy. Neutrophils > 1500; platelets > 100000; haemoglobin > 10 mg/dL. Adequate renal and hepatic functions, with serum creatinine < 1.2 mg/dl and total bilirubin < 2 mg/dl. Adequate contraceptive methods during the study and up to 3 months after. Adequate cardiac function assessed by physical exam, electrocardiogram and left ventricular ejection fraction > 55%. Exclusion Criteria: Inflammatory carcinoma or stage I, II or IV breast cancer disease. Males. Active infection. Other neoplasms except for basal skin carcinoma or cervical in situ carcinoma adequately treated. Other previous neoplasms are allowed if diagnosed and treated more than 5 years before study registration. Concomitant serious disease provoking organ failure (heart, renal, hepatic, respiratory). Pre-existing motor or sensorial neuropathy > grade 1. Inability for treatment compliance. History of hypersensitivity to compounds such as cremophor, cyclosporine or vitamin K. History of arrhythmias or congestive heart failure, even when controlled; or active cardiac blocking of second or third grade. History of myocardial infarction in the previous 6 months. Hypertension not controlled. Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Gemcitabine + Adriamycine + Paclitaxel<br>Neoadjuvant chemotherapy consisted of adriamycine 40 mg/m2, administered on day 1 as an i.v. infusion. Paclitaxel 150 mg/m2 was administered on day 2 as an i.v infusion followed by gemcitabine 2000 mg/m2 as an i.v. infusion. The three drugs were administered every two weeks for 6 cycles. | Drug: Gemcitabine<br> <br> * Other names: Gemzar;Drug: Adriamycine<br> <br> * Other names: doxorubicin;Drug: Paclitaxel<br> <br> * Other names: Taxol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete response (pCR) rate | pCR is defined as no invasive cells identifiable in breast sections at surgery. Response will be measured by physical exam and breast imaging before surgery and will be evaluated according to the World Health Organization (WHO) criteria. Pathological response after surgery, will be based on the proportion of remaining tumor and post-chemotherapy changes, evaluating separately the response in the breast and in the axilla lymph nodes. | Up to week 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | Tumor response is defined as the percentage of patients with a complete or partial response out of the patients who had measurable disease at baseline. | Up to week 12 | 
| Conservative surgery rate | To determine the percentage of conservative surgery rate versus other surgery | Up to week 15 | 
| The Number of Participants Who Experienced Adverse Events (AE) | According to the Common Terminology Criteria for Adverse Events (CTCAE) version 2.0 | Through study treatment up to surgery | 
| Disease-free survival | Time from the start of treatment to the progression of the disease (if it happens) | Up to 5 years since surgery | 
| Tissue molecular markers and their correlation with response | Evaluation of changes in the tumor marker profile before and after treatment in tumor samples obtained before and after chemotherapy treatment. | Up to week 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoadjuvant chemotherapy., Stage III disease.