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

NCT ID: NCT01301612

Last Updated: 2014-07-14

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31

Brief Summary

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.

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.

Conditions

Carcinoma; Adenocarcinoma; Uterine Cervix Adenosquamous Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Cisplatin

Intervention Type: DRUG

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

Radiation Therapy

Intervention Type: RADIATION

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

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.

Group Type: EXPERIMENTAL

Nimotuzumab

Intervention Type: DRUG

Nimotuzumab, 200 mg, IV, Weekly doses for 14 weeks

Cisplatin

Intervention Type: DRUG

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

Brachytherapy

Intervention Type: RADIATION

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.

Interventions

Nimotuzumab

Nimotuzumab, 200 mg, IV, Weekly doses for 14 weeks

Intervention Type: DRUG

Cisplatin

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

Intervention Type: DRUG

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.

Intervention Type: RADIATION

Cisplatin

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

Intervention Type: DRUG

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

Intervention Type: RADIATION

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Eurofarma Laboratorios S.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sergio Lago

Role: PRINCIPAL_INVESTIGATOR

Núcleo de Novos Tratamentos em Câncer - NNTC

Locations

Centro de Pesquisa Clínica da Liga Norte Riograndense contra o Câncer

Natal, Rio Grande do Norte, Brazil

Hospital de Caridade de Ijui - ONCOSITE Centro de Pesquisa Clínica em Oncologia

Ijuí, Rio Grande do Sul, Brazil

Hospital Santa Rita - Núcleo de Novos Tratamentos em Câncer

Porto Alegre, Rio Grande do Sul, Brazil

Caism - Unicamp

Campinas, São Paulo, Brazil

Centro de Pesquisas Clínicas da Fundação Amaral Carvalho

Jaú, São Paulo, Brazil

ICESP

São Paulo, São Paulo, Brazil

Hospital Santa Marcelina

São Paulo, São Paulo, Brazil

Countries

Brazil

Other Identifiers

EF 110

Identifier Type: -

Identifier Source: org_study_id