Neoadjuvant Sequential Administration of Two Gemcitabine Combinations in Operable Breast Cancer

Study Overview
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Brief Summary
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Gemcitabine and anthracycline combination has shown encouraging activity as neoadjuvant chemotherapy in locally advanced breast cancer. An addition of sequential gemcitabine and cisplatin, also a highly active combination in this indication, may result in improvement in pathological response and overall survival. Patients with operable breast cancer will be treated in neoadjuvant setting with gemcitabine plus doxorubicin, followed by gemcitabine plus cisplatin.

Official Title
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Neoadjuvant Administration of Gemcitabine Plus Doxorubicin Followed by Gemcitabine Plus Cisplatin in Large or Locally Advanced Operable Breast Cancer: A Phase II Study

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: gemcitabine
* Drug: doxorubicin
* Drug: cisplatin
* Procedure: surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of breast carcinoma No previous chemotherapy, with bidimensionally measurable locally advanced disease Adequate performance status (Karnofsky Performance Status [KPS] greater than or equal to 70), bone marrow reserves, hepatic, cardiac and renal functions. Exclusion Criteria: Inflammatory breast cancer Pregnancy and Breast-feeding Serious concomitant disorder or infection Previous cancer within the last 5 years or a second primary malignancy.

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gemcitabine+Doxorubicin+Cisplatin+Surgery<br>Gemcitabine: 1200 mg/m^2, intravenous (IV) day 1 and day 8 every 21 days x 4 cycles (1-4) then 1000 mg/m^2, IV, day 1 and day 8 every 21 days x 4 cycles (5-8). Doxorubicin: 60 mg/m^2, IV, every 21 days x 4 cycles (1-4). Cisplatin: 70 mg/m^2, IV, every 21 days x 4 cycles (5-8). Surgery follows 8 cycles of chemotherapy. Extent and type of surgery is guided by tumor size, physician and/or patient decision. | Drug: gemcitabine<br>* 1200 mg/m^2, intravenous (IV) day 1 and day 8 every 21 days x 4 cycles (1-4) then 1000 mg/m^2, IV, day 1 and day 8 every 21 days x 4 cycles (5-8)<br>* Other names: Gemzar;Drug: doxorubicin<br>* 60 mg/m^2, IV, every 21 days x 4 cycles (1-4)<br>Drug: cisplatin<br>* 70 mg/m^2, IV, every 21 days x 4 cycles (5-8)<br>Procedure: surgery<br>* Surgery follows 8 cycles of chemotherapy. Extent and type of surgery is guided by tumor size, physician and/or patient decision.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Pathological Complete Response (Pathological Complete Response Rate) | Complete pathological response: No invasive tumor cells identified from sections from site of previous cancer. Require evidence corroborating prior presence of invasive cancer, which requires detection of abnormal fibroelastic breast stroma devoid of normal lobular units and contains foamy macrophages with moderate numbers of fibroblasts and mononuclear inflammatory cells. Presence of nondescript collagenised lobules or breast fibrous tissue is not evidence that tumor site has been adequately sampled and macroscopic assessment and sampling is needed until original neoplastic stroma identified. | tumor assessment at baseline and during surgery after eight 21-day treatment cycles | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of Deaths During Study |  | baseline through last cycle on study drug (eight 21-day cycles) | 
| Progression Free Survival (PFS) | PFS was defined as the date of enrollment to the first date of documented disease progression or death from any cause. Because the median was not reached, results are presented as the Outcome: Number of Participants with Disease Progression or Death at Various Timepoints. | baseline to measured progressive disease or death from any cause (up to 68 months) | 
| Overall Survival | Overall survival was defined as the date of enrollment to the date of death from any cause. Because the median was not reached, results will be presented as the Outcome: Number of Participants who Died from Any Cause at Various Timepoints. | baseline to date of death from any cause up to 68 months | 
| Time to Treatment Failure | Time to treatment failure was defined as the time from study enrollment to the first observation of disease progression, death as a result of any cause, or early discontinuation of treatment. Time to treatment failure was censored at the date of the last follow-up visit for patients who did not discontinue early, who were still alive, and who have not progressed. Because the upper limit of the 95% Confidence Interval of median survival was not calculable, results are presented as the Outcome: Number of Participants with Time to Treatment Failure at Various Timepoints. | baseline to stopping treatment (up to 68 months) | 
| Number of Patients Eligible for Breast Conservation Surgery at Baseline and Number of Patients Undergoing Breast Conservation Surgery | The extent and type of surgery was guided by the tumor size, physician and/or patient decision. It was either conservation surgery or mastectomy with axillary lymph node dissection. Results are reported on the number of patients who underwent breast conservation surgery. | baseline, after eight 21-day cycles of study drug |