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Assessment of Gemcitabine as Chemoradiotherapy in Patients With Locally Advanced Carcinoma of Cervix and Renal Disease

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ClinicalTrials.gov Identifier: NCT03101995
Recruitment Status : Recruiting
First Posted : April 5, 2017
Last Update Posted : March 30, 2018
Sponsor:
Collaborators:
Instituto Nacional de Cardiologia Ignacio Chavez
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Information provided by (Responsible Party):
Dr. Lucely Cetina Pérez, National Institute of Cancerología

Brief Summary:
From the global burden of Cervical Cancer (CC), 85% occurs in developing countries, representing 12% of cancer in women. In Mexico CC ranks second in incidence and mortality among women. The National Institute of Cancer in Mexico (lNCAN) receives annually about 500 patients with CC, 80% of which are diagnosed with locally advanced disease. Furthermore, 10 to 20% of these present kidney deterioration. The main reason for kidney disease is ureteral obstruction, other causes include age and comorbidities, such as diabetes and hypertension. The standard treatment for locally advanced disease consists in concomitant chemo-radiotherapy based on cisplatin (QT-RT), followed by brachytherapy, with an absolute benefit of 10%. However, the use of cisplatin in patients with renal disease may be questionable, considering it is a nephrotoxic treatment. Given that renal dysfunction limits the standard treatment efficiency because of the widely known nephrotoxicity of cisplatin, in most Cancer Centers of our country, patients with renal dysfunction receive only radiation therapy, even though it has proven less effective than concomitant QT-RT, limiting disease-free and overall survival of these patients. Venook et al. used gemcitabine as a radiosensitizer in patients with cancer and renal dysfunction. Our group, has observed encouraging results using gemcitabine as an alternative to cisplatin in concomitant treatment with radiotherapy, in CC patients with renal insufficiency. 89% of patients had complete response and improvement in renal function, with an enhanced creatinine clearance after treatment. Therefore, it is necessary to explore the safety of gemcitabine as an alternative treatment for CC patients with locally advanced disease and renal deterioration. We propose this clinical trial to assess the safety of treatment with gemcitabine and specifically on renal function in patients with renal deterioration. It is important to take into consideration that CC in advanced stages produces pain, transvaginal fetid discharge and general discomfort. It also causes side effects secondary to renal failure such as nausea, vomiting, fatigue, anemia, among others. These effects have a significant impact on the quality of life of these patients. Cancer treatment and its side effects, besides the implications of a nephrostomy catheter or ileostomy bag, determine the deterioration in the quality of life of the patient, during and sometimes after treatment. Thus it is of utmost importance to evaluate the factors that could help improve the quality of life of patients and explore the factors that deteriorate it. This clinical trial aims to generate scientific evidence to help make the best decisions concerning the treatment of patients with cervical cancer and renal impairment, and the impact on their quality of life.

Condition or disease Intervention/treatment Phase
Cervical Cancer Drug: Gemcitabine Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Phase II open, single arm, national, non-randomized clinical trial; to evaluate safety of gemcitabine in patients with locally advanced cervical cancer and renal dysfunction, referring to the INCAN.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Clinical Trial to Evaluate the Potential of Concomitant Chemoradiotherapy With Gemcitabine in Patients With Locally Advanced Carcinoma of Cervix and Renal Disease
Actual Study Start Date : January 16, 2018
Estimated Primary Completion Date : March 30, 2019
Estimated Study Completion Date : July 1, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Gemcitabine
Gemcitabine doses: 300 mg/m2/week for 6 weeks.
Drug: Gemcitabine

Gemcitabine 300 mg/m2, prepared in 0.5 liters of sodium chloride 0.9%, IV administered in 30 minutes weekly for a maximum of 6 weeks.

Radiotherapy will start the first week, or as soon as the blood count is normal or the patient has recovered after blood transfusion. Radiotherapy will be applied, using an external beam releasing 40-50.4 Gy in 20-28 fractions: 1.8 Gy/day for 5 days/week, during 4 to 6 weeks.

Intracavitary brachytherapy will be added to reach a total EQD2 dosage (α/β=10) of 78-86 Gy.

Other Name: Gemzar




Primary Outcome Measures :
  1. Glomerular Filtration Rate [ Time Frame: During and every 3 months after completing concomitant QT/RT treatment, for the first two years, and every 6 months for the following 3 years. ]

    Safety of gemcitabine regarding renal function will be assessed through glomerular filtration rate.

    An improvement of 10 ml/min/1.73m2 as compared to basal glomerular rate is expected by the end of treatment.



Secondary Outcome Measures :
  1. Toxicity [ Time Frame: During and every 3 months after completing concomitant QT/RT treatment, for the first two years, and every 6 months for the following 3 years. ]
    Toxicity will be evaluated according to the toxicity criteria of CTCEA v. 4.03. A toxicity index of <4 is expected during treatment.



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

Inclusion criteria.

  1. Patients who give their written consent to participate in the study.
  2. Women, 18-70 years of age, considering the following criteria:

    • In women of childbearing age: i. Negative serum pregnancy test at baseline (14 days prior to the start of QT-RT).

    ii. The patient must accept the use of any contraceptive method approved by the attending physician during the study and 12 weeks after the end of treatment.

    • Postmenopausal women must meet at least one of the following parameters for eligibility: i. Prior bilateral oophorectomy ii. Age ≥ 60 years iii. Age < 60 years, with amenorrhea for at least 12 months and levels of follicle stimulating hormone and estradiol within postmenopausal parameters.

  3. Diagnosed with CC IB2-IVA, with or without retroperitoneal lymph nodes (para-aortic), smaller than 2 cm.
  4. With histologic confirmation of squamous carcinoma, adenosquamous carcinoma, adenocarcinoma or glassy cells carcinoma.
  5. Without previous treatment and medically able to receive gemcitabine.
  6. Disease measurable by CT and/or MRI according to RECIST (v1.1) criteria.
  7. Functional status of 0-3 according to WHO criteria.
  8. Renal dysfunction defined by glomerular filtration (GF) <60 ml/min/1.73m2 calculated by the CKD-EPI formula.
  9. Normal hematologic and liver function, as defined by the following parameters:

    • Hemoglobin > 10g/L. (Transfusion prior to the treatment is allowed to reach this level of hemoglobin).
    • Leucocytes > 4000/mm3.
    • Platelets > 100,000/mm3.
    • Total Bilirubin ≤1.5 times the upper normal limit (UNL).
    • Transaminases < 1.5 times the UNL.
  10. Normal PA chest radiograph.

Exclusion criteria.

  1. Patients with prior or concomitant malignancy, except non-melanoma skin carcinoma.
  2. Patients with diabetes and/or hypertension with retinopathy or albuminuria >300.
  3. Patients with evidence of active TB infection.
  4. Patients infected with Human Immunodeficiency Virus (HIV).
  5. Patients with a history of Systemic Lupus Erythematosus and other rheumatologic diseases that cause kidney damage.
  6. Patients with vesicovaginal or vesicorectal fistula at the time of diagnosis.
  7. Patients with uncontrolled intercurrent diseases including active infections that contraindicate QT, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, decompensated diabetes, difficult control hypertension and psychiatric illness.
  8. Concomitant treatment with other experimental drugs.
  9. Social, family or geographical conditions that suggest a poor adherence to the study.

Study discontinuation criteria.

  1. Evidence of disease progression, if the researcher considers that the patient would benefit more with other therapy.
  2. At the request of the patient.
  3. By unacceptable toxicity.
  4. Pregnancy.

Violation of starting criteria. Criteria must be followed punctually. If a patient were inappropriately included, she must be discontinued from the study.


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): NCT03101995


Contacts
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Contact: Lucely C Cetina, MD, M.Sc. +5215554851237 lucelycetina.incan@gmail.com
Contact: Roberto Jiménez, MD, M.Sc. +5215554851237 jilir@yahoo.com.mx

Locations
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Mexico
National Institute of Cancer Recruiting
Mexico City, DF, Mexico, 14080
Contact: Lucely Cetina, MD, MSc    +521555 4851237    micuentalucely@yahoo.com   
Sponsors and Collaborators
National Institute of Cancerología
Instituto Nacional de Cardiologia Ignacio Chavez
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Investigators
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Principal Investigator: Lucely C Cetina, MD, M.Sc. National Institute of Cancerología

Publications:

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Responsible Party: Dr. Lucely Cetina Pérez, MD, Master of Science, National Institute of Cancerología
ClinicalTrials.gov Identifier: NCT03101995     History of Changes
Other Study ID Numbers: NationalIC
INCAN ( Other Identifier: Instituto Nacional de Cancerología )
First Posted: April 5, 2017    Key Record Dates
Last Update Posted: March 30, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Dr. Lucely Cetina Pérez, National Institute of Cancerología:
Treatment
Locally advanced cervical cancer
Renal failure
Gemcitabine

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