Study of Nimotuzumab, Radiation Therapy and Cisplatin Versus Radiation Therapy and Cisplatin for Treatment of Stage IB e IVA UCC(CORUS)

This study has suspended participant recruitment.
(Regulatory requirement. A phase III study is being designed.)
Sponsor:
Information provided by (Responsible Party):
Eurofarma Laboratorios S.A.
ClinicalTrials.gov Identifier:
NCT01301612
First received: February 21, 2011
Last updated: May 3, 2013
Last verified: January 2012
  Purpose

The primary study objective will be to assess the efficacy of the combination of radiation therapy with nimotuzumab and cisplatin, as compared to the combination of radiation therapy plus cisplatin in the treatment of Uterine Cervical Carcinoma (UCC).

The secondary study objectives will be safety and tolerability evaluations, to determine treatment feasibility and the interim efficacy evaluation according to other parameters routinely used in oncology.


Condition Intervention Phase
Carcinoma
Adenocarcinoma
Uterine Cervix Adenosquamous Carcinoma
Drug: Nimotuzumab
Drug: Cisplatin
Radiation: Brachytherapy
Radiation: Radiation Therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Multicenter, Randomized,Two-Arm Clinical Study: An Investigational Arm Containing Nimotuzumab in Combination With Radiotion Therapy and Cisplatyn, and a Control Arm With Radiation Therapy and Cisplatin for the Definitive Treatment of Stage IB and IVA Uterine Cervical Carcinoma

Resource links provided by NLM:


Further study details as provided by Eurofarma Laboratorios S.A.:

Primary Outcome Measures:
  • Local control of disease [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Local control of disease will be measured by magnetic resonance imaging (MRI), clinical gynecological examinations, as well as by biopsy (if indicated), 12 weeks after treatment end.


Secondary Outcome Measures:
  • Complete clinical response rate [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    • Overall survival;
    • Distant disease-free survival;
    • Progression-free survival;
    • Local control of long-term disease; Frequency of treatment-emergent adverse events; o Frequency of severe treatment-emergent adverse events.


Estimated Enrollment: 108
Study Start Date: January 2011
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Radiation therapy and Cisplatin
Cisplatin, 40 mg/m2, IV - Weekly doses for 6 weeks Pelvic radiation therapy, 45 Gy External, Fractions of 1.8 Gy per day, 5 days a week Dose boosts,15 Gy ± 5%, External, Daily fractions of 1.8 Gy or 2 Gy per day, 5 days a week Brachytherapy (if indicaed), 40 Gy at spot A(low dose rate), Intracavitary 1 or 2 separate fractions for 1 to 3 weeks. 28 Gy at spot A, (high dose rate) Intracavitary,4 fractions of 7.0 Gy once or twice a week.
Drug: Cisplatin
Cisplatin, 40 mg/m2, IV. Weekly doses for 6 weeks
Radiation: Radiation Therapy

Pelvic radiation therapy: 45 Gy, External, Fractions of 1.8 Gy per day, 5 days a week.

Dose boosts: 15 Gy ± 5%, External, Daily fractions of 1.8 Gy or 2 Gy per day, 5 days a week.

Brachytherapy 40 Gy at spot A(low dose rate.) Intracavitary 1 or 2 separate fractions for 1 to 3 weeks.

28 Gy at spot A (high dose rate, Intracavitary, 4 fractions of 7.0 Gy once or twice a week

Experimental: Nimotuzumab and

Cisplatin, 40 mg/m2, IV, Weekly doses for 6 weeks.

Nimotuzumab, 200 mg, Diluted into 250 mL of sodium chloride sterile solution 0.9% in intravenous infusion for 30 minutes, Weekly doses for 14 weeks.

Pelvic radiation therapy, 45 Gy, External, Fractions of 1.8 Gy per day, 5 days a week.

Dose boosts, 15 Gy ± 5%, External,Daily fractions of 1.8 Gy or 2 Gy per day, 5 days a week

Brachytherapy (In case there is indication, should it be performed, not to be longer than the expected 70 days for the entire radiation therapy), 40 Gy at spot A (low dose rate) Intracavitary 1 or 2 separate fractions for 1 to 3 weeks 28 Gy at spot A (high dose rate), Intracavitary, 4 fractions of 7.0 Gy once or twice a week.

Drug: Nimotuzumab
Nimotuzumab, 200 mg, IV, Weekly doses for 14 weeks
Drug: Cisplatin
Cisplatin, 40 mg/m2, IV, Weekly doses for 6 weeks
Radiation: Brachytherapy

Brachytherapy: 40 Gy at spot A(low dose rate, Intracavitary, 1 or 2 separate fractions for 1 to 3 weeks.

Brachytherapy: 28 Gy at spot A (high dose rate), Intracavitary 4 fractions of 7.0 Gy once or twice a week.


Detailed Description:

This will be a phase II, randomized, controlled, open-label, multicenter, and two-arm study. The study will be conducted in Brazil and has the purpose of determining the activity and safety of nimotuzumab in terms of overall and distant disease-free survival, radiological and clinical gynecological examinations, as well as by biopsy, if indicated, progression-free survival, local control of long-term disease, frequency of treatment-emergent adverse events, frequency of severe treatment-emergent adverse events.

All participating patients will sign a consent form before they undergo any study-related procedure.The eligible patients will have stage IB and IVA uterine cervical carcinoma and they will be randomized to one of two treatment groups.

Randomization and treatment assignment will be performed by a company specifically contracted for such purpose and will be per research site and disease stage (IB2 to IIIA versus IIIB to IVA), 1:1.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > 18 years;
  • Diagnosis of histologically confirmed stages IB2 (> 4 cm) to IVA prickle-cell carcinoma or adenocarcinoma or uterine cervix adenosquamous carcinoma, according to FIGO system,7 (see Appendix A for guidance about staging);
  • Measurable disease according to RECIST 1.139 or at least disease evaluable through imaging methods and/or gynecological examination (magnetic resonance imaging (MRI) scans within six weeks prior to randomization will be accepted, computed tomography will accepted in case MRI is contraindicated);
  • Indication of definitive treatment with chemotherapy and radiation therapy, at the investigator's discretion;
  • Performance status < 2, according to the Eastern Cooperative Oncology Group criteria 40 (ECOG; see Appendix C);
  • Adequate body functions, indicated by:Serum creatinine < 1.2 mg/100 mL; Creatinine clearance > 60 mL/min (estimate); Bilirubin up to 1.5-fold the upper limit of normal (ULN) and transaminases, alkaline phosphatase and gamma-glutamyltransferase up to 2.5-fold the ULN; Leucocytes > 3,000/μL; Neutrophils > 1,500/μL; Hemoglobin > 10 g/dL; Platelets > 80,000/μL;
  • Signed informed consent form.

Exclusion Criteria:

  • Para-aortic lymph nodes involvement through radiological and/or surgical staging, at investigator's discretion;
  • Current severe comorbidity that, in the investigator's opinion, would put the patient at a significantly higher risk or will jeopardize protocol compliance;
  • Current bowel inflammatory disease;
  • Current major neurological or psychiatric disease, including clinically significant dementia and seizures, at the investigator's discretion;
  • Known hypersensitivity or allergic reactions to study treatment;
  • Current uncontrolled hypercalcemia (> 11,5 mg/dL, that is, grade > 1 according to Common Terminology Criteria for Adverse Events [CTCAE] v4.02, of US National Cancer Institute)41;
  • Know HIV positive status (enrollment of patients with hepatitis B or C is at the investigator's discretion);
  • Pregnancy or lactation;
  • Female patients, as well as their partners, who wish to become pregnant or are unwilling to use an appropriate contraceptive method throughout the study period.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01301612

Locations
Brazil
Centro de Pesquisa Clínica da Liga Norte Riograndense contra o Câncer
Natal, Rio Grande do Norte, Brazil, 59075740
Hospital de Caridade de Ijui - ONCOSITE Centro de Pesquisa Clínica em Oncologia
Ijui, Rio Grande do Sul, Brazil, 98700000
Hospital Santa Rita - Núcleo de Novos Tratamentos em Câncer
Porto Alegre, Rio Grande do Sul, Brazil, 90020-160
Caism - Unicamp
Campinas, São Paulo, Brazil, 13083970
Centro de Pesquisas Clínicas da Fundação Amaral Carvalho
Jau, São Paulo, Brazil, 17210000
Hospital Santa Marcelina
São Paulo, Brazil, 08270070
ICESP
São Paulo, Brazil, 01246000
Sponsors and Collaborators
Eurofarma Laboratorios S.A.
Investigators
Principal Investigator: Sergio Lago Núcleo de Novos Tratamentos em Câncer - NNTC
  More Information

No publications provided

Responsible Party: Eurofarma Laboratorios S.A.
ClinicalTrials.gov Identifier: NCT01301612     History of Changes
Other Study ID Numbers: EF 110
Study First Received: February 21, 2011
Last Updated: May 3, 2013
Health Authority: Brazil: National Committee of Ethics in Research
Brazil: National Health Surveillance Agency

Keywords provided by Eurofarma Laboratorios S.A.:
carcinoma or adenocarcinoma or uterine cervix adenosquamous carcinoma

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Carcinoma, Adenosquamous
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Complex and Mixed
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 22, 2014