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

Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01301612
• Other study ID #: EF 110
• Status: Withdrawn
• Phase: Phase 2
• First received: February 21, 2011
• Last updated: July 10, 2014
• Start date: January 2011

Study information

• Verified date: January 2012
• Source: Eurofarma Laboratorios S.A.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in ResearchBrazil: National Health Surveillance Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Carcinoma, Adenosquamous
• Uterine Cervix Adenosquamous Carcinoma

Intervention

Drug:
• Nimotuzumab
Nimotuzumab, 200 mg, IV, Weekly doses for 14 weeks
• 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.

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

Locations

Country	Name	City	State
Brazil	Caism - Unicamp	Campinas	São Paulo
Brazil	Hospital de Caridade de Ijui - ONCOSITE Centro de Pesquisa Clínica em Oncologia	Ijui	Rio Grande do Sul
Brazil	Centro de Pesquisas Clínicas da Fundação Amaral Carvalho	Jau	São Paulo
Brazil	Centro de Pesquisa Clínica da Liga Norte Riograndense contra o Câncer	Natal	Rio Grande do Norte
Brazil	Hospital Santa Rita - Núcleo de Novos Tratamentos em Câncer	Porto Alegre	Rio Grande do Sul
Brazil	Hospital Santa Marcelina	São Paulo
Brazil	ICESP	São Paulo

Sponsors (1)

Lead Sponsor	Collaborator
Eurofarma Laboratorios S.A.

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes