Preoperative Treatment of Breast Cancer With Two Different Sequential Treatment Regimens

Study Overview
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Brief Summary
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An open-label randomized Phase II study in order to explore two different sequential anthracycline-based neoadjuvant treatment regimens in female patients with primary, operable breast cancer (T2-T4/N0-2/M0).

Official Title
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A Randomized Phase 2 Trial of Doxorubicin Plus Pemetrexed Followed by Docetaxel, Versus Doxorubicin Plus Cyclophosphamide Followed by Docetaxel, as Neoadjuvant Treatment for Early Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: pemetrexed
* Drug: cyclophosphamide
* Drug: doxorubicin
* Drug: docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of primary early breast cancer, tumor size greater than or equal to 2 centimeters (cm), of Stages T2-T4/N0-2. Performance status 0-2 Eastern Cooperative Oncology Group (ECOG). Adequate organ function (bone marrow, hepatic, renal, cardiac). Exclusion Criteria: Prior anthracyclines as part of prior anticancer therapy. Concurrent antitumor therapy. Second primary malignancy. Serious concomitant systemic disorder. Pre-existing sensorial or motor neuropathy Grade 1.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A: Pemetrexed Plus Doxorubicin, Followed by Docetaxel<br> | Drug: pemetrexed<br>* 500 mg/m^2, intravenous (IV), every 21 days, 4 cycles (1-4)<br>* Other names: LY231514, Alimta;Drug: doxorubicin<br>* 60 mg/m^2, intravenous (IV), every 21 days, 4 cycles (1-4)<br>Drug: docetaxel<br>* 100 mg/m^2, intravenous (IV), every 21 days, 4 cycles (5-8)<br>|
| Active Comparator: B: Cyclophosphamide Plus Doxorubicin, Followed by Docetaxel<br> | Drug: cyclophosphamide<br>* 600 mg/m2, intravenous (IV), every 21 days, 4 cycles (1-4)<br>Drug: doxorubicin<br>* 60 mg/m^2, intravenous (IV), every 21 days, 4 cycles (1-4)<br>Drug: docetaxel<br>* 100 mg/m^2, intravenous (IV), every 21 days, 4 cycles (5-8)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Pathological Complete Response | pathological assessment of tissue removed during surgery to determine if tumor tissue is still present after chemotherapy | surgery after eight 21-day cycles of chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Clinical Tumor Response After the First Sequence of Chemotherapy | The number of participants with a clinical tumor response based on measurement of tumor size after the first sequence of chemotherapy, without a second confirmatory tumor measurement, per protocol. | Cycles 1-4 (21-day cycles) | 
| Number of Participants With a Clinical Tumor Response After the Second Sequence of Chemotherapy | The number of participants with a clinical tumor response based on measurement of tumor size after the second sequence of chemotherapy, without a second confirmatory tumor measurement required, per protocol. | Cycles 5-8 (21-day cycles) | 
| Number of Patients With Histologically Negative Axillary Lymph Node Status at Surgery | Histologically negative is defined as no malignant cells present in the axillary lymph nodes during surgery. | surgery after eight 21-day cycles of chemotherapy | 
| Disease-free Survival | Disease-free survival is defined as the time from date of study enrollment (randomization) to first date of progressive disease (PD) or death from any cause. PD per Response Evaluation Criteria In Solid Tumors (RECIST) criteria is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. For patients not known to have died as of the data cut-off date and who do not have progressive disease, disease-free survival was censored at the last contact date. | baseline through post surgery, follow-up for 3 years post-surgery (up to 5.2 years after randomization) |