Exploratory Study of Sunitinib Malate as a Component of Neoadjuvant Therapy for Breast Cancer

Study Overview
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Brief Summary
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The combination of paclitaxel, doxorubicin, and cyclophosphamide is a standard neoadjuvant (given before surgery) treatment for patients that have either inoperable or operable breast cancer. This treatment can help shrink the tumors so they can be removed to help prevent the cancer from spreading to other parts of the body. This study is being done to test the impact of adding sunitinib as a single-agent (Segment 1), followed by sunitinib plus paclitaxel (Segment 2), followed by doxorubicin and cyclophosphamide (Segment 3). We hope the addition of sunitinib will make the treatment more effective, but we don't know if this is true.

Official Title
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An Exploratory Study of the Biological and Clinical Activity of Sunitinib Malate as a Component of Neoadjuvant Therapy for Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: sunitinib alone
* Drug: sunitinib plus paclitaxel
* Drug: doxorubicin and cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically-confirmed adenocarcinoma of the breast with operable or inoperable stage 1c (primary tumor > 1.0 cm), II or III disease. Measurable disease by physical examinations or diagnostic breast imaging (mammography, ultrasonography or MR). Pre-treatment core or incisional biopsy. Patients may not have had definitive primary surgery. Male or female, 18 years of age or older. ECOG performance status 0 or 1. Adequate organ function as defined in the protocol. Exclusion Criteria: Prior radiation therapy, cytotoxic therapy or systemic therapy for breast cancer. Prior use of tamoxifen or raloxifene as chemoprevention is allowed but must be discontinued prior to study entry. Metastatic (Stage IV) breast cancer Patients who have had only a pre-treatment fine needle aspiration (FNA) are excluded. Current therapeutic treatment on another clinical trial with an investigational agent. Any of the following within the 6 months prior to starting study treatment: -myocardial infarction -severe/unstable angina -coronary/peripheral artery bypass graft -congestive heart failure -cerebrovascular accident including transient ischemic attack -pulmonary embolus Ongoing cardiac dysrhythmias of NCI CTCAE grade >=2, atrial fibrillation of any grade, or QTc interval >450 msec for males or >470 msec for females. Hypertension that cannot be controlled by medications. Current treatment with therapeutic doses of any anti-coagulant. Prophylactic use of anticoagulants is allowed. Known human immunodeficiency virus (HIV) infection. Pregnancy or breastfeeding. All female patients with reproductive potential must have a negative pregnancy test prior to first day of study medication. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: 1<br>The study will be conducted in 3 sequential treatment segments. | Drug: sunitinib alone<br>* sunitinib alone (segment 1): During the first segment, patients will receive single-agent sunitinib for 2 weeks.<br>Drug: sunitinib plus paclitaxel<br>* sunitinib plus paclitaxel (Segment 2): Following Segment 1, patients will begin the second segment, 4 cycles (16 weeks) of neoadjuvant treatment with the combination of sunitinib and paclitaxel.<br>Drug: doxorubicin and cyclophosphamide<br>* doxorubicin and cyclophosphamide (Segment 3): Following Segment 2, patients will receive 4 cycles (8 weeks) of neoadjuvant treatment with AC.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Interstitial Fluid Pressure (IFP) Induced by Sunitinib Monotherapy | Participants had their tumor IFP measured at baseline, after sunitinib monotherapy (segment 1) and after sunitinib+paclitaxel (segment 2). This outcome measure is the difference of the mean value from the end of segment 1 (sunitinib monotherapy) and the mean baseline value. | baseline through end of segment 1 (2 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Interstitial Fluid Pressure (IFP) Induced by Paclitaxel Plus Sunitinib After Sunitinib Monotherapy | Participants had their tumor IFP measured at baseline, after sunitinib monotherapy (segment 1) and after sunitinib+paclitaxel (segment 2). This outcome measure is the difference of the mean value from the end of segment 2 (paclitaxel/sunitinib therapy through cycle 5) and end of segment 1 (sunitinib monotherapy) mean value. | end of cycle 1 (sunitinib monotherapy) to end of cycle 5 (paclitaxel/sunitinib therapy) (112 days) | 
| Pathological Complete Response (pCR) Rate for Patients Treated With Sunitinib/Paclitaxel Followed by AC as Neoadjuvant Therapy for Breast Cancer |  | screening through surgery | 
| To Evaluate the Safety of Paclitaxel Plus Sunitinib When Given in Combination as Neoadjuvant Therapy | This measure determines the number of patients who had Grade 3/4 Adverse Events that were related to treatment while the patient was on paclitaxel plus sunitinib. | end of cycle 1 (sunitinib monotherapy) to end of cycle 5 (paclitaxel/sunitinib therapy) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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newly diagnosed breast cancer, neoadjuvant therapy