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
Overview
- Phase
- Phase 2
- Intervention
- Cisplatin
- Conditions
- Carcinoma
- Sponsor
- Eurofarma Laboratorios S.A.
- Locations
- 7
- Primary Endpoint
- Local control of disease
- Status
- Withdrawn
- Last Updated
- 11 years ago
Overview
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.
Investigators
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.
Arms & Interventions
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.
Intervention: Cisplatin
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.
Intervention: Radiation Therapy
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.
Intervention: Nimotuzumab
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.
Intervention: Cisplatin
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.
Intervention: Brachytherapy
Outcomes
Primary Outcomes
Local control of disease
Time Frame: 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 Outcomes
- Complete clinical response rate(3 years)