Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer Patients
Condition: Cancer of Cervix
MeSH terms: Uterine Cervical Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      The propose of this study is to determine if neoadjuvant chemotherapy followed by
      chemoradiation is safe and effective in locally advanced cervical cancer patients. Moreover,
      the study would determine if there is any association between hENT1 expression and response
      rate to gemcitabine.
    

Detailed description: 
      The study has been developed and executed at Medicina Integral Prof. Fernando Figueira
      Institute - IMIP since September/2013. The primary objective is to evaluate the safety of
      neoadjuvant chemotherapy based in gemcitabine followed by chemoradiation in cervical cancer
      patients. Data has been collected at medical oncology clinic, where patients have medical
      visits and receive chemotherapy treatment. New cases of cervical cancer patients are analysed
      for eligibility criteria. When matching these criteria, the protocol is explained, its
      participation is offered and consent form is explained, highlighting the voluntary aspect of
      the process. If there is agreement in participation, two consent forms are provided and
      signed. Patients receive one copy and the other one goes to his/her medical record. All
      demographic, social and medical data is recorded.

      Patients are considered to have the first visit on the day they sign consent agreement form,
      when they are also referred to radiooncologist visit. Up to 30-business days they should
      complete staging (MRI, PET-SCAN, labs) and initiate neoadjuvant chemotherapy. Before each
      day, of each cycle, patients are seen by medical oncologist and nurse, when toxicity data is
      collected. Before and after neoadjuvant chemotherapy, there is a clinical evaluation
      performed by the gynecologic oncologist to evaluate clinical response. During chemoradiation,
      patients have weekly visits. The treatment is completed with brachytherapy, and 30-days after
      its completion, another clinical evaluation is done. After 90 days of completion treatment,
      pelvic MRI and PET-SCAN are repeated and considered to determine response rate.

      Biopsies samples have been collected. The investigators intend to perform immunohistochemical
      analysis at the end of recruitment and identify any association between hENT1 expression and
      outcomes.

      Information is collected by principal investigator in EXCEL forms, during medical visits.
      Toxicity data has been analyzed every 3 months by a data monitoring committee comprising two
      medical oncologists, one radiooncologist and a gynecological nurse. All unexpected event is
      related to this committee and also to the Research Ethics Committee of IMIP. Patients are
      followed up 3/3 months. Inconsistent or missing data will be re-checked in medical records.

      This is a phase IIa study with only one arm of intervention. Since response rates observed in
      phase III studies with concomitant platin based chemoradiation is 85% in average, and given
      that response rate using gemcitabin based adjuvant chemotherapy, after chemoradiation, is
      96.5%, the investigators calculated the sample size of 49 patients. It was considered an
      alpha error of 5% and 80% power. Descriptive analyses of variables of this population will be
      held. The normal numerical variables are described as mean +/- standard deviation. The
      non-parametric numeric variables are described as median (interquartile range). Categorical
      data will be described as a percentage of the total. The progression free survival and
      overall survival will be obtained by Kaplan-Meier method, using the computer program Epinfo.
    

Intervention name(s): gemcitabine; cisplatin; chemoradiation
Intervention type(s): Drug; Drug; Radiation
Intervention description(s): Patients received intravenous 500-1000 ml normal saline and antiemetic medication before chemotherapy. Treatment consisted of intravenous gemcitabine at a dose of 1000 mg/m2 diluted in 500 ml of normal saline administered over 30 minutes mg/m2 diluted in 500 ml of normal saline administered over 30 minutes on days 1 and 8, followed by cisplatin 35 mg/m2 administered over 2 hours on day 1 and 8.; 35 mg/m2 administered over 2 hours on day 1 and 8.; external beam radiotherapy concomitant with weekly cisplatin 40mg/m2
Other intervention name(s): Gemzar and cisplatin neoadjuvant chemotherapy
Intervention MeSH terms: Cisplatin; Gemcitabine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: cervix neoplasm; hENT1 protein, human; Chemotherapy