Positron Emission Tomography Using 3'-Deoxy-3'-(18F) Fluorothymidine in Treating Women With Locally Advanced Cancer in One Breast Who Are Receiving Chemotherapy

Study Overview
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Brief Summary
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RATIONALE: Diagnostic procedures, such as positron emission tomography (PET) using 3'-deoxy-3'-(18F) fluorothymidine, may be effective in assessing the response to chemotherapy before surgery in treating locally advanced breast cancer. PURPOSE: This clinical trial is studying how well positron emission tomography using 3'-deoxy-3'-(18F) fluorothymidine works in treating women with locally advanced cancer in one breast who are receiving chemotherapy.

Detailed Description
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OBJECTIVES: Primary Evaluate the efficacy of positron emission tomography (PET) utilizing 3'-deoxy-3'-(18F) fluorothymidine (^18F-FLT) to correctly identify response to neoadjuvant chemotherapy in women with locally advanced unilateral breast cancer. Correlate PET-^18F-FLT results with histological response. Secondary Evaluate the correlation of early changes in tumor uptake of ^18F-FLT after the first course of chemotherapy with complete response after treatment completion. Evaluate the correlation of early changes in tumor uptake of ^18F-FLT with histologic response in biopsies obtained after 1 course of chemotherapy. Determine if the initial intensity of tumor uptake is a predictive value of response to chemotherapy. Determine if initial intensity of tumor uptake of ^18F-FLT varies according to histologic type of tumor, indices of proliferation, and tumor cellularity before therapy. Determine if the tumor uptake of ^18F-FLT during therapy varies according to histologic type of tumor, indices of proliferation, and tumor cellularity before therapy. Evaluate the role of TK1 on the kinetics of ^18 F-FLT. Analyze serum. Research biomarkers of genomics, transcription, and proteomics. Evaluate the toxicity of ^18F-FLT. OUTLINE: This is a multicenter study. Patients receive 3'-deoxy-3'-(18F) fluorothymidine (^18F-FLT) IV and undergo positron emission tomography (PET) before the first and second courses of neoadjuvant chemotherapy. Patients receiving bisequential chemotherapy undergo ^18F-FLT-PET before the change in drugs (usually the fourth or fifth course). All patients undergo a final ^18F-FLT-PET after the last chemotherapy course but before surgery. After completion of study therapy, patients are followed for 1 month.

Official Title
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Study of Positron Emission Tomography With 3'-Deoxy-3'-[18F] Fluoro-thymidine ([18F]-FLT) for the Evaluation of Response to Neoadjuvant Chemotherapy for Cancers of the Breast

Conditions
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Breast Cancer

Intervention / Treatment
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* Other: 3'-deoxy-3'-[18F]fluorothymidine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Inclusion criteria: Histologically confirmed unilateral breast cancer T2 or T3, any N, M0 Unifocal by mammography and ultrasound Negative for c-erbB2 by immunohistochemistry (IHC) Planning neoadjuvant chemotherapy comprising anthracyclines and/or taxanes, alone or combined Measurable disease by ultrasound Hormone receptor status not specified Exclusion criteria: Bilateral disease Multifocal tumor Invasive grade I lobular cancer Metastatic disease Stage ≥ T4 disease Cutaneous invasion, major adherence, or inflammatory disease Tumor overexpressing c-erbB2 by IHC (HER 2+++) Suspected clinical or radiological lesion (examined or not) PATIENT CHARACTERISTICS: Inclusion criteria: ECOG performance status 0-1 Female Menopausal status not specified Hematologic, hepatic, and renal function normal Not pregnant or nursing Fertile patients must use effective contraception Exclusion criteria: Alcohol dependency or prior reaction to ethanol injection Impossible to receive study therapy due to geographical, social, or psychological reasons Prisoners or patients under supervision PRIOR CONCURRENT THERAPY: Inclusion criteria: See Disease Characteristics Exclusion criteria: Participation in another concurrent therapeutic study with an experimental drug

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TEP FLT<br> | Other: 3'-deoxy-3'-[18F]fluorothymidine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intensity of tumor uptake of 3'-deoxy-3'-(18F) fluorothymidine (18F-FLT) determined visually and correlated with histological or surgical response according to Sataloff criteria |  | Post surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intensity of tumor uptake of 18F-FLT by standardized uptake value (SUV) |  | Post surgery | 
| Variation of tumoral uptake as seen by positron emission tomography (PET) before, during, and after therapy as determined visually and by SUV |  | Post surgery | 
| Intensity of the tumoral uptake of 18F-FLT on initial exam visually and by SUV |  | post surgery | 
| Histologic parameters: type, grade, mitotic index, CCIS , and microbiopsy embols after first course of chemotherapy (and on microbiopsy before therapeutic change of sequence in patients receiving bisequential chemotherapy) |  | post surgery | 
| Immunohistochemical evaluation (estrogen and progesterone receptors, c-erbB2, Ki-67, e-cadherin) |  | Post-surgery | 
| Rate of thymidine kinase 1 (TK1) |  | Post surgery | 
| Toxicity by CTC-AE v. 3.0 |  | Post surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II breast cancer, stage IIIA breast cancer