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

NCT03101995 | Recruiting Phase 2 DMC

• 2 other identifiers: NationalICINCAN
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Cervical Cancer

Keywords

Treatment; Locally advanced cervical cancer; Renal failure; Gemcitabine

Outcome Measures

Primary Outcomes (1)

• Glomerular Filtration Rate

  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.

  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.

Secondary Outcomes (1)

• Toxicity of gemcitabine in patients with carcinoma of cervix and renal disease

  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.

Study Arms (1)

Gemcitabine

EXPERIMENTAL

Gemcitabine doses: 300 mg/m2/week for 6 weeks.

Drug: Gemcitabine

Interventions

Gemcitabine DRUG

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.

Also known as: Gemzar

Gemcitabine

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who give their written consent to participate in the study.
• 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.
• Diagnosed with CC IB2-IVA, with or without retroperitoneal lymph nodes (para-aortic), smaller than 2 cm.
• With histologic confirmation of squamous carcinoma, adenosquamous carcinoma, adenocarcinoma or glassy cells carcinoma.
• Without previous treatment and medically able to receive gemcitabine.
• Disease measurable by CT and/or MRI according to RECIST (v1.1) criteria.
• Functional status of 0-3 according to WHO criteria.
• Renal dysfunction defined by glomerular filtration (GF) \<60 ml/min/1.73m2 calculated by the CKD-EPI formula.
• 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.

You may not qualify if:

• Patients with prior or concomitant malignancy, except non-melanoma skin carcinoma.
• Patients with diabetes and/or hypertension with retinopathy or albuminuria \>300.
• Patients with evidence of active TB infection.
• Patients infected with Human Immunodeficiency Virus (HIV).
• Patients with a history of Systemic Lupus Erythematosus and other rheumatologic diseases that cause kidney damage.
• Patients with vesicovaginal or vesicorectal fistula at the time of diagnosis.
• 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.
• Concomitant treatment with other experimental drugs.
• Social, family or geographical conditions that suggest a poor adherence to the study.
• Study discontinuation criteria.
• Evidence of disease progression, if the researcher considers that the patient would benefit more with other therapy.
• At the request of the patient.
• By unacceptable toxicity.
• Pregnancy.
• Violation of starting criteria. Criteria must be followed punctually. If a patient were inappropriately included, she must be discontinued from the study.

Sponsors & Collaborators

• National Institute of Cancerología: lead
• Instituto Nacional de Cardiologia Ignacio Chavez: collaborator
• Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran: collaborator

Study Sites (1)

National Institute of Cancer

Mexico City, Mexico City, 14080, Mexico

RECRUITING

Related Publications (14)

• Green JA, Kirwan JM, Tierney JF, Symonds P, Fresco L, Collingwood M, Williams CJ. Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and meta-analysis. Lancet. 2001 Sep 8;358(9284):781-6. doi: 10.1016/S0140-6736(01)05965-7.

  PMID: 11564482 BACKGROUND

• Brown JM. Carbogen and nicotinamide: expectations too high? Radiother Oncol. 1992 Jun;24(2):75-6. doi: 10.1016/0167-8140(92)90281-x. No abstract available.

  PMID: 1386679 BACKGROUND

• Zarba JJ, Jaremtchuk AV, Gonzalez Jazey P, Keropian M, Castagnino R, Mina C, Arroyo G; GETICS (Grupo de Estudio, Tratamiento e Investigacion del Cancer del Sur) Argentina. A phase I-II study of weekly cisplatin and gemcitabine with concurrent radiotherapy in locally advanced cervical carcinoma. Ann Oncol. 2003 Aug;14(8):1285-90. doi: 10.1093/annonc/mdg345.

  PMID: 12881394 BACKGROUND

• Duenas-Gonzalez A, Lopez-Graniel C, Gonzalez A, Reyes M, Mota A, Munoz D, Solorza G, Hinojosa LM, Guadarrama R, Florentino R, Mohar A, Melendez J, Maldonado V, Chanona J, Robles E, De la Garza J. A phase II study of gemcitabine and cisplatin combination as induction chemotherapy for untreated locally advanced cervical carcinoma. Ann Oncol. 2001 Apr;12(4):541-7. doi: 10.1023/a:1011117617514.

  PMID: 11398890 BACKGROUND

• Chang PY, Dai MS, Ho CL, Yao NS. Administration of gemcitabine and cisplatin in cancer patients with renal failure under hemodialysis. J BUON. 2013 Oct-Dec;18(4):1058-61.

  PMID: 24344039 BACKGROUND

• Pattaranutaporn P, Thirapakawong C, Chansilpa Y, Therasakvichya S, Ieumwananontachai N, Thephamongkhol K. Phase II study of concurrent gemcitabine and radiotherapy in locally advanced stage IIIB cervical carcinoma. Gynecol Oncol. 2001 Jun;81(3):404-7. doi: 10.1006/gyno.2001.6197.

  PMID: 11371129 BACKGROUND

• Bosch A, Frias Z, Valda GC. Prognostic significance of ureteral obstruction in carcinoma of the cervix uteri. Acta Radiol Ther Phys Biol. 1973 Feb;12(1):47-56. doi: 10.3109/02841867309131091. No abstract available.

  PMID: 4725645 BACKGROUND

• Cetina L, Rivera L, Candelaria M, de la Garza J, Duenas-Gonzalez A. Chemoradiation with gemcitabine for cervical cancer in patients with renal failure. Anticancer Drugs. 2004 Sep;15(8):761-6. doi: 10.1097/00001813-200409000-00004.

  PMID: 15494637 BACKGROUND

• Rose PG, Ali S, Whitney CW, Lanciano R, Stehman FB. Impact of hydronephrosis on outcome of stage IIIB cervical cancer patients with disease limited to the pelvis, treated with radiation and concurrent chemotherapy: a Gynecologic Oncology Group study. Gynecol Oncol. 2010 May;117(2):270-5. doi: 10.1016/j.ygyno.2010.01.045. Epub 2010 Feb 24.

  PMID: 20181381 BACKGROUND

• Tomimaru Y, Eguchi H, Satoh T, Tomokuni A, Asaoka T, Wada H, Marubashi S, Ogawa K, Takehara T, Mori M, Doki Y, Nagano H. Feasibility of pre-operative chemoradiotherapy with gemcitabine to treat pancreatic cancer in patients with impaired renal function. Jpn J Clin Oncol. 2015 Apr;45(4):343-8. doi: 10.1093/jjco/hyu224. Epub 2015 Jan 14.

  PMID: 25589454 BACKGROUND

• Venook AP, Egorin MJ, Rosner GL, Hollis D, Mani S, Hawkins M, Byrd J, Hohl R, Budman D, Meropol NJ, Ratain MJ. Phase I and pharmacokinetic trial of gemcitabine in patients with hepatic or renal dysfunction: Cancer and Leukemia Group B 9565. J Clin Oncol. 2000 Jul;18(14):2780-7. doi: 10.1200/JCO.2000.18.14.2780.

  PMID: 10894879 BACKGROUND

• Tanji N, Fukumoto T, Miura N, Yanagihara Y, Shirato A, Azuma K, Miyauchi Y, Kikugawa T, Shimamoto K, Yokoyama M. Combined chemotherapy with gemcitabine and carboplatin for metastatic urothelial carcinomas in patients with high renal insufficiency. Int J Clin Oncol. 2013 Oct;18(5):910-5. doi: 10.1007/s10147-012-0466-9. Epub 2012 Aug 31.

  PMID: 22936563 BACKGROUND

• Grigsby PW. Cervical cancer: combined modality therapy. Cancer J. 2001 Jul-Aug;7 Suppl 1:S47-50.

  PMID: 11504285 BACKGROUND

• Zahra MA, Taylor A, Mould G, Coles C, Crawford R, Tan LT. Concurrent weekly cisplatin chemotherapy and radiotherapy in a haemodialysis patient with locally advanced cervix cancer. Clin Oncol (R Coll Radiol). 2008 Feb;20(1):6-11. doi: 10.1016/j.clon.2007.10.007. Epub 2008 Jan 11.

  PMID: 18191389 BACKGROUND

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Renal Insufficiency

Interventions

Gemcitabine

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Lucely C Cetina, MD, M.Sc.

  National Institute of Cancerología

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lucely C Cetina, MD, M.Sc.

CONTACT

+5215554851237; lucelycetina.incan@gmail.com

Roberto Jiménez, MD, M.Sc.

CONTACT

+5215554851237; jilir@yahoo.com.mx

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Master of Science

Model Details: 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.

Study Record Dates

• First Submitted: December 15, 2016
• First Posted: April 5, 2017
• Study Start: January 16, 2018
• Primary Completion: July 1, 2025
• Study Completion: November 1, 2025
• Last Updated: May 28, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)