Pilot Study of 18F Fluoropaclitaxel (FPAC)
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Multidrug resistance (MDR) is a cause of treatment failure in many cancer patients. MDR
      refers to a phenotype whereby a tumor is resistant to a large number of natural
      chemotherapeutic drugs. Having prior knowledge of the presence of such resistance would
      decrease morbidity from unsuccessful therapy and allow for the selection of individuals who
      may benefit from co-administration of MDR inhibiting drugs. The Tc-99m labeled single photon
      emitting radiotracers sestamibi and tetrofosmin have shown some predictive value. However,
      positron-emitting (PET) radiotracers, which allow for dynamic, quantitative imaging, hold the
      promise of more accurate and specific identification of MDR tumors.

      Objective:

      To obtain human safety data, to demonstrate imaging feasibility with FPAC, to obtain human
      biodistribution and to obtain preliminary evidence of breast tumor uptake concordance with
      response to therapy.
    

Detailed description: 
      18F flouropaclitaxel (FPAC) distribution in malignant tumors is expected to be similar to
      that of paclitaxel. It is proposed that by monitoring the influx and efflux of FPAC in vivo
      using PET imaging, we will be able to determine if a tumor retains the drug (is drug
      sensitive) or pumps it out (is drug resistant). The efflux rate of FPAC in the tumor should
      be proportional the amount of Pgp present and therefore should be a predictor of treatment
      failure. If this method is successful at identifying MDR, patients can be spared a course of
      ineffective chemotherapy and can be started on alternative drugs or, if available, an
      effective MDR modulator can be administered prior to treatment.

      In order to validate the biodistribution in non-human primate, 3 normal volunteers will be
      recruited to participate in a dosimetry PET imaging protocol.

      Often, patients with breast cancer are treated with chemotherapy prior to definitive surgical
      removal of the primary tumor. Three patients with breast cancer who are candidates for this
      neoadjuvant chemotherapy will also be recruited to participate in this study, in order to
      demonstrate the feasibility of tumor imaging. As these patients will be receiving
      chemotherapy (likely paclitaxel), a preliminary correlation with FPAC uptake and tumor
      response can also be attempted in this pilot study.

      Primary Objective

      --To obtain human dosimetry and monitor for potential physiologic effects following 4-[F-18]
      fluoropaclitaxel (FPAC) administration

      Secondary Objectives

        -  a.To characterize tracer uptake in tumors and normal tissues and develop robust methods
           for analysis of FPAC kinetics in breast tumors

        -  b.To optimize the imaging protocol for FPAC, and, if feasible, reduce to 1 or 2 static
           scans
    

Intervention name(s): 4- [F-18] fluoropaclitaxel
Intervention type(s): Drug
Intervention description(s): 4- [F-18] fluoropaclitaxel, <84 micrograms, <10 mCi, IV followed by PET/CT imaging
Other intervention name(s): FPAC
Intervention model: Single Group Assignment
Masking: None (Open Label)
Keywords: PET; multidrug resistance; fluoropaclitaxel; paclitaxel; breast cancer; dosimetry; imaging feasibility