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Trial record 3 of 5 for:    10202164 [PUBMED-IDS]

Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02309658
Recruitment Status : Completed
First Posted : December 5, 2014
Last Update Posted : October 16, 2015
Sponsor:
Collaborator:
Instituto Nacional de Cancer, Brazil
Information provided by (Responsible Party):
Carla Rameri Alexandre Silva de Azevedo, Professor Fernando Figueira Integral Medicine Institute

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.

Condition or disease Intervention/treatment Phase
Cancer of Cervix Drug: gemcitabine Drug: cisplatin Radiation: chemoradiation Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Primary Completion Date : October 2015
Study Completion Date : October 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cervical Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Interventional
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.
Drug: gemcitabine
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
Drug: cisplatin
35 mg/m2 administered over 2 hours on day 1 and 8.
Radiation: chemoradiation
external beam radiotherapy concomitant with weekly cisplatin 40mg/m2



Primary Outcome Measures :
  1. 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.

  2. 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.



Secondary Outcome Measures :
  1. Disease free survival [ Time Frame: One year of follow up. ]
    From recruitment date to relapse date.

  2. Overall Survival [ Time Frame: One year of follow up. ]
    From recruitment date to death.

  3. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

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


Locations
Brazil
Instituto de Medicina Integral Fernando Figueira
Recife, Pernambuco, Brazil, 50070550
Sponsors and Collaborators
Professor Fernando Figueira Integral Medicine Institute
Instituto Nacional de Cancer, Brazil
Investigators
Principal Investigator: Carla Rameri A. de Azevedo, MD IMIP

Publications:

Responsible Party: Carla Rameri Alexandre Silva de Azevedo, MD, Medical Oncologist, Professor Fernando Figueira Integral Medicine Institute
ClinicalTrials.gov Identifier: NCT02309658     History of Changes
Other Study ID Numbers: U1111-1156-1640
First Posted: December 5, 2014    Key Record Dates
Last Update Posted: October 16, 2015
Last Verified: October 2015

Keywords provided by Carla Rameri Alexandre Silva de Azevedo, Professor Fernando Figueira Integral Medicine Institute:
cervix neoplasm
hENT1 protein, human
Chemotherapy

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Gemcitabine
Cisplatin
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs