Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer Patients
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|ClinicalTrials.gov Identifier: NCT02309658|
Recruitment Status : Completed
First Posted : December 5, 2014
Last Update Posted : October 16, 2015
|Condition or disease||Intervention/treatment||Phase|
|Cancer of Cervix||Drug: gemcitabine Drug: cisplatin Radiation: chemoradiation||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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 Start Date :||September 2013|
|Actual Primary Completion Date :||October 2015|
|Actual Study Completion Date :||October 2015|
Treatment consisted of gemcitabine at a dose of 1000 mg/m2, followed by cisplatin 35 mg/m2 administered on day 1 and 8, for two cycles. After that, weekly cisplatin 40mg/m2 is administered concomitant with radiotherapy (45-55Gy) in 1,8-2,0 daily fractions and a 10Gy boost when there was parametrial involvement. Low-dose rate brachytherapy, in 4 fractions of 7Gy, in a total of 28Gy will complete the protocol.
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.
Other Name: Gemzar and cisplatin neoadjuvant chemotherapy
35 mg/m2 administered over 2 hours on day 1 and 8.
external beam radiotherapy concomitant with weekly cisplatin 40mg/m2
- Toxicity will be evaluated with Common Terminology Criteria for Adverse Events (CTCAE 4,0). [ Time Frame: Up to 4 weeks after brachytherapy ]Toxicity will be recorded before each day of chemotherapy and weekly during radiotherapy.
- Response rate (Response Evaluation Criteria in Solid Tumors (RECIST) criteria with pelvic MRI and PET-CT) [ Time Frame: 12 weeks after treatment ]
Response will be evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) criteria with pelvic MRI and PET-CT.
Immediately after neoadjuvant chemotherapy and 30 days after brachytherapy, clinical response will also be evaluated.
- Disease free survival [ Time Frame: One year of follow up. ]From recruitment date to relapse date.
- Overall Survival [ Time Frame: One year of follow up. ]From recruitment date to death.
- hENT1 expression [ Time Frame: At the end of recruitment, expected to be at 24 months after study beginning ]hENT1 will be analysed by immunohistochemistry. Scoring for hENT1 was based on staining intensities and the proportion of cancer cells. Islet cells of pancreas tissue served as an external positive control for hENT1 immunohistochemistry, and lymphocytes or endothelial cells surrounding the tumour area served as internal positive controls. Carcinoma was then evaluated by comparison with the internal controls. Staining intensity was graded as: 0, absent; 1+, positive but less intense than internal control tissue; 2+, positive as in internal control tissue; and 3+,positive, more intense than internal control tissue. Samples with regions of varying staining intensities of hENT1 were scored and the percentages of each region were recorded. Finally, tumours with an intensity staining of 3+in≥50% of the tumour cells were considered as showing high expression of hENT1.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02309658
|Instituto de Medicina Integral Fernando Figueira|
|Recife, Pernambuco, Brazil, 50070550|
|Principal Investigator:||Carla Rameri A. de Azevedo, MD||IMIP|