Clinical trial NCT02309658: Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer Patients
Official title: Safety and Efficacy of Gemcitabine Based Neoadjuvant Chemotherapy Followed by Chemoradiation in Locally Advanced Cervical Cancer Patients and Association With Human Equilibrative Nucleoside Transporter 1 (hENT1) Expression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cancer of Cervix
Keywords: cervix neoplasm
hENT1 protein, human
Chemotherapy
Lead sponsor: Professor Fernando Figueira Integral Medicine Institute
Sponsor class: OTHER
Collaborators: name: Instituto Nacional de Cancer, Brazil
First posted: 2014-12-05
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Histological confirmed diagnostic of cervical carcinoma
* International Federation of Gynecology and Obstetrics (FIGO) stage Ib2 (\>4cm) to IVa
* Performance status 0-2 (ECOG scale)
* Hemoglobin \>10g/dl , neutrophil \> 1500 /mm3, platelet \>100.000/mm3
* Creatinine \< 1,5 mg/dl
* Bilirubin total \<1,6 mg/dl and liver enzymes (AST e ALT) \< 2x (upper limit of normal)
* Informed consent.

Exclusion Criteria:

* Cervical tumors with adenocarcinoma, adenosquamous and small cell adenocarcinoma histology
* Distant metastasis including paraortic nodes
* Pregnancy and breast-feeding
* Previous chemotherapy, radiotherapy or uterine surgery
* Relevant co-morbidity which prevent chemotherapy use
* Previous neoplasia, except non-melanoma skin cancer

Primary outcomes:
measure: Toxicity will be evaluated with Common Terminology Criteria for Adverse Events (CTCAE 4,0).
timeFrame: Up to 4 weeks after brachytherapy
measure: Response rate (Response Evaluation Criteria in Solid Tumors (RECIST) criteria with pelvic MRI and PET-CT)
timeFrame: 12 weeks after treatment
Secondary outcomes:
measure: Disease free survival
timeFrame: One year of follow up.
measure: Overall Survival
timeFrame: One year of follow up.
measure: hENT1 expression
timeFrame: At the end of recruitment, expected to be at 24 months after study beginning
Other outcomes:
Locations:
city: Recife
country: Brazil
facility: Instituto de Medicina Integral Fernando Figueira
state: Pernambuco
Study officials:
affiliation: IMIP
name: Carla Rameri A. de Azevedo, MD
role: PRINCIPAL_INVESTIGATOR
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