Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer Patients

NCT02309658 | Completed Phase 2 DMC

• 1 other identifier: U1111-1156-1640
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Cancer of Cervix

Keywords

cervix neoplasm; hENT1 protein, human; Chemotherapy

Outcome Measures

Primary Outcomes (2)

• Toxicity will be evaluated with Common Terminology Criteria for Adverse Events (CTCAE 4,0).

  Toxicity will be recorded before each day of chemotherapy and weekly during radiotherapy.

  Up to 4 weeks after brachytherapy

• Response rate (Response Evaluation Criteria in Solid Tumors (RECIST) criteria with pelvic MRI and PET-CT)

  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.

  12 weeks after treatment

Secondary Outcomes (3)

• Disease free survival

  One year of follow up.

• Overall Survival

  One year of follow up.

• hENT1 expression

  At the end of recruitment, expected to be at 24 months after study beginning

Study Arms (1)

Interventional

EXPERIMENTAL

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; Drug: cisplatin; Radiation: chemoradiation

Interventions

gemcitabine DRUG

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.

Also known as: Gemzar and cisplatin neoadjuvant chemotherapy

Interventional

cisplatin DRUG

35 mg/m2 administered over 2 hours on day 1 and 8.

Interventional

chemoradiation RADIATION

external beam radiotherapy concomitant with weekly cisplatin 40mg/m2

Interventional

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Professor Fernando Figueira Integral Medicine Institute: lead
• Instituto Nacional de Cancer, Brazil: collaborator

Study Sites (1)

Instituto de Medicina Integral Fernando Figueira

Recife, Pernambuco, 50070550, Brazil

Location

Related Publications (15)

• Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol. 2008 Dec 10;26(35):5802-12. doi: 10.1200/JCO.2008.16.4368. Epub 2008 Nov 10.

  PMID: 19001332 BACKGROUND

• Eifel PJ, Winter K, Morris M, Levenback C, Grigsby PW, Cooper J, Rotman M, Gershenson D, Mutch DG. Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for high-risk cervical cancer: an update of radiation therapy oncology group trial (RTOG) 90-01. J Clin Oncol. 2004 Mar 1;22(5):872-80. doi: 10.1200/JCO.2004.07.197.

  PMID: 14990643 BACKGROUND

• Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. doi: 10.3322/caac.20107. Epub 2011 Feb 4.

  PMID: 21296855 BACKGROUND

• Kies MS, Haraf DJ, Athanasiadis I, Kozloff M, Mittal B, Pelzer H, Rademaker AW, Wenig B, Weichselbaum RR, Vokes EE. Induction chemotherapy followed by concurrent chemoradiation for advanced head and neck cancer: improved disease control and survival. J Clin Oncol. 1998 Aug;16(8):2715-21. doi: 10.1200/JCO.1998.16.8.2715.

  PMID: 9704722 BACKGROUND

• Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC Jr, Clarke-Pearson DL, Liao SY. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol. 1999 May;17(5):1339-48. doi: 10.1200/JCO.1999.17.5.1339.

  PMID: 10334517 BACKGROUND

• Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. doi: 10.1056/NEJM199904153401502.

  PMID: 10202165 BACKGROUND

• Pearcey R, Brundage M, Drouin P, Jeffrey J, Johnston D, Lukka H, MacLean G, Souhami L, Stuart G, Tu D. Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. J Clin Oncol. 2002 Feb 15;20(4):966-72. doi: 10.1200/JCO.2002.20.4.966.

  PMID: 11844818 BACKGROUND

• Neoadjuvant Chemotherapy for Locally Advanced Cervical Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy for locally advanced cervical cancer: a systematic review and meta-analysis of individual patient data from 21 randomised trials. Eur J Cancer. 2003 Nov;39(17):2470-86. doi: 10.1016/s0959-8049(03)00425-8.

  PMID: 14602133 BACKGROUND

• Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, Rotman M, Gershenson DM, Mutch DG. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1137-43. doi: 10.1056/NEJM199904153401501.

  PMID: 10202164 BACKGROUND

• Duenas-Gonzalez A, Rivera L, Mota A, Lopez-Graniel C, Guadarrama A, Gonzalez A, Chanona G, Cabrera P, de la Garza J. The advantages of concurrent chemoradiation after neoadjuvant chemotherapy for locally advanced cervical carcinoma. Arch Med Res. 2002 Mar-Apr;33(2):201-2. doi: 10.1016/s0188-4409(01)00358-7. No abstract available.

  PMID: 11886723 RESULT

• 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 RESULT

• Matsumura N, Nakamura Y, Kohjimoto Y, Inagaki T, Nanpo Y, Yasuoka H, Ohashi Y, Hara I. The prognostic significance of human equilibrative nucleoside transporter 1 expression in patients with metastatic bladder cancer treated with gemcitabine-cisplatin-based combination chemotherapy. BJU Int. 2011 Jul;108(2 Pt 2):E110-6. doi: 10.1111/j.1464-410X.2010.09932.x. Epub 2010 Dec 16.

  PMID: 21166756 RESULT

• Giovannetti E, Del Tacca M, Mey V, Funel N, Nannizzi S, Ricci S, Orlandini C, Boggi U, Campani D, Del Chiaro M, Iannopollo M, Bevilacqua G, Mosca F, Danesi R. Transcription analysis of human equilibrative nucleoside transporter-1 predicts survival in pancreas cancer patients treated with gemcitabine. Cancer Res. 2006 Apr 1;66(7):3928-35. doi: 10.1158/0008-5472.CAN-05-4203.

  PMID: 16585222 RESULT

• Duenas-Gonzalez A, Zarba JJ, Patel F, Alcedo JC, Beslija S, Casanova L, Pattaranutaporn P, Hameed S, Blair JM, Barraclough H, Orlando M. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011 May 1;29(13):1678-85. doi: 10.1200/JCO.2009.25.9663. Epub 2011 Mar 28.

  PMID: 21444871 RESULT

• Borbath I, Verbrugghe L, Lai R, Gigot JF, Humblet Y, Piessevaux H, Sempoux C. Human equilibrative nucleoside transporter 1 (hENT1) expression is a potential predictive tool for response to gemcitabine in patients with advanced cholangiocarcinoma. Eur J Cancer. 2012 May;48(7):990-6. doi: 10.1016/j.ejca.2011.11.006. Epub 2011 Dec 1.

  PMID: 22137164 RESULT

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Gemcitabine; Cisplatin; Chemoradiotherapy

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

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Study Officials

• Carla Rameri A. de Azevedo, MD

  IMIP

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 1, 2014
• First Posted: December 5, 2014
• Study Start: September 1, 2013
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: October 16, 2015

Record last verified: 2015-10

Locations

BR (1)