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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Adenocarcinoma; Carcinoma; Uterine Cervix Adenosquamous Carcinoma
• Intervention / Treatment: Drug: Cisplatin; Drug: Cisplatin; Radiation: Radiation Therapy; Drug: Nimotuzumab; Radiation: Brachytherapy

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 01246000
    • ICESP
  • São Paulo, Brazil, 08270070
    • Hospital Santa Marcelina
  • Rio Grande do Norte
    • Natal, Rio Grande do Norte, Brazil, 59075740
      • Centro de Pesquisa Clínica da Liga Norte Riograndense Contra o Câncer
  • Rio Grande do Sul
    • Ijui, Rio Grande do Sul, Brazil, 98700000
      • Hospital de Caridade de Ijui - ONCOSITE Centro de Pesquisa Clínica em Oncologia
    • Porto Alegre, Rio Grande do Sul, Brazil, 90020-160
      • Hospital Santa Rita - Núcleo de Novos Tratamentos em Câncer
  • São Paulo
    • Campinas, São Paulo, Brazil, 13083970
      • Caism - Unicamp
    • Jau, São Paulo, Brazil, 17210000
      • Centro de Pesquisas Clínicas da Fundação Amaral Carvalho

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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; 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: Cisplatin; Cisplatin, 40 mg/m2, IV, Weekly doses for 6 weeks; Drug: Cisplatin; Cisplatin, 40 mg/m2, IV. Weekly doses for 6 weeks; Drug: Nimotuzumab; Nimotuzumab, 200 mg, IV, Weekly doses for 14 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local control of disease	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.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete clinical response rate	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.	3 years

Collaborators and Investigators

• Sponsor: Eurofarma Laboratorios S.A.
• Investigators: Principal Investigator: Sergio Lago, Núcleo de Novos Tratamentos em Câncer - NNTC

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: February 21, 2011
• First Submitted That Met QC Criteria: February 22, 2011
• First Posted (Estimate): February 23, 2011

Study Record Updates

• Last Update Posted (Estimate): July 14, 2014
• Last Update Submitted That Met QC Criteria: July 10, 2014
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: carcinoma or adenocarcinoma or uterine cervix adenosquamous carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Complex and Mixed; Carcinoma; Adenocarcinoma; Carcinoma, Adenosquamous; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cisplatin; Nimotuzumab
• Other Study ID Numbers: EF 110