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

Sponsor

Eurofarma Laboratorios S.A. (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT01301612

Collaborator

(none)

Enrollment

Locations

Arms

Patients Per Site

Study Details

Study Description

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.

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

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

Jan 1, 2011

Anticipated Primary Completion Date :

Dec 1, 2017

Arms and Interventions

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 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.

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

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.

Outcome Measures

Primary Outcome Measures

Local control of disease [1 year]
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 [3 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Centro de Pesquisa Clínica da Liga Norte Riograndense contra o Câncer	Natal	Rio Grande do Norte	Brazil	59075740
2	Hospital de Caridade de Ijui - ONCOSITE Centro de Pesquisa Clínica em Oncologia	Ijui	Rio Grande do Sul	Brazil	98700000
3	Hospital Santa Rita - Núcleo de Novos Tratamentos em Câncer	Porto Alegre	Rio Grande do Sul	Brazil	90020-160
4	Caism - Unicamp	Campinas	São Paulo	Brazil	13083970
5	Centro de Pesquisas Clínicas da Fundação Amaral Carvalho	Jau	São Paulo	Brazil	17210000
6	ICESP	São Paulo		Brazil	01246000
7	Hospital Santa Marcelina	São Paulo		Brazil	08270070