Study Comparing Radiation Therapy and Chemotherapy With or Without Nimotuzumab

Study Overview
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Brief Summary
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Primary: to compare the overall survival defined as the time elapsed between the randomization date and death due to any cause, in both treatment groups. Secondary: to compare the progression-free survival, incidence of locoregional failure, site of the first recurrence/progression, objective response rate assessment, quality of life assessment and incidence of adverse events.

Detailed Description
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This is a phase III, superiority, national, open-label, randomized, and two-arm study. Patients' enrollment will be performed only after approval by competent regulatory authorities and it will last up to 12 months. All patients taking part in the study must sign an informed consent. The patients will have stage III or IV, unresectable head and neck SCC, performance status 0 or 1. Randomization and treatment assignment will be performed by a company specifically contracted for such purpose and will be per research site and disease stage, 1:1

Official Title
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A Phase III Study Evaluating the Standard Radiation Therapy and Chemotherapy Regimen, With or Without Nimotuzumab, in Unresectable, Locally Advanced Epidermoid Carcinoma of the Head and Neck

Conditions
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Carcinoma, Head and Neck Cancer

Intervention / Treatment
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* Radiation: Radiation Therapy
* Drug: Nimotuzumab
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Aged 18 to 75 years old; Histological or cytological confirmation of SCC in oral cavity, oropharynx, hypopharynx, or larynx; Stages III or IV disease Unresectability according to responsible surgeon or medical staff's opinion; Performance status 0 or 1 Present indication for radiation therapy and chemotherapy treatment with cisplatin; Adequate hepatic, renal and medullar functions, indicated by: Life expectancy above 6 months. Exclusion Criteria Presence of nasopharyngeal, paranasal sinuses, or salivary glands carcinoma; Presence of known distant metastasis; Presence of any other active neoplasm or history of any tumor diagnosed in the last 5 years Patients with inability to eat normally, in whom a gastric or enteral tubing was not possible at least 2 weeks before their enrollment in the study; Previous treatment with chemotherapy, radiation therapy, or EGFR inhibitors of any pharmacological class; Presence of serious comorbidity that, in the investigator's opinion, will put the patient at risk or will jeopardize protocol compliance; Active known seropositivity for HIV, hepatitis B or C Presence of a significant neurological or psychiatric disease, as per the investigator's judgment; Hypersensitivity or allergy to any of the study treatments; Presence of uncontrolled hypercalcemia; Pregnancy or breastfeeding; Female patients of childbearing potential who wish to become pregnant or are unwilling, as well as their partners, to use an appropriate contraceptive method throughout the study period; Participation in any clinical trial in the last 12 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radiation therapy, cisplatin and nimotuzumab<br>Nimotuzumab - (Diluted into 250 mL of sodium chloride sterile solution 0.9% in intravenous infusion for 30 minutes. Pre-drugs are optional, at the investigator's discretion)- 200 mg, IV, weekly doses during the radiation therapy until completing 6 months. Radiation therapy- 66 -70 Gy, external,fractions of 2 Gy per day, 5 days a week Cisplatin - 75 mg/m2, IV, Doses every 3 weeks (a total of three doses) | Drug: Nimotuzumab<br>* 200 mg, IV, weekly doses during the radiation therapy until completing 6 months (Diluted into 250 mL of sodium chloride sterile solution 0.9% in intravenous infusion for 30 minutes).<br>|
| Active Comparator: Radiation therapy and cisplatin<br>Radiation therapy: 66- 70 Gy, fractions of 2 Gy per day, 5 days a week Cisplatin:75 mg/m2, IV, doses every 3 weeks (a total of three doses) | Radiation: Radiation Therapy<br>* 66- 70 Gy External, Fractions of 2.0 Gy per day, 5 days a week<br>Drug: Cisplatin<br>* 75 mg/m2, IV, doses every 3 weeks (a total of three doses)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Local control of disease will be measured by magnetic resonance imaging (MRI) and physical examination 6 weeks after treatment end. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete clinical response rate | Progression-free survival; Incidence of locoregional failure; Site of the first recurrence or progression; Objective response rate assessment; EORTC quality of life questionnaires assessment; Incidence of several adverse events; | 2 years |