- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01216020
Cetuximab Plus Radiotherapy Versus Cisplatin Plus Radiotherapy in Locally Advanced Head and Neck Cancer (CTXMAB+RT)
Multiinstitutional Open Label Randomized Phase II Study Comparing Cetuximab and Radiotherapy Versus Cisplatin and Radiotherapy as Firstline Treatment for Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck (LA-NHSCC)
BACKGROUND:
Concomitant radiotherapy and cisplatin (CDDP) based chemotherapy is the standard treatment for LA-NHSCC. This combined modality treatment is linked with considerable acute local and systemic toxicity.EGFR is overexpressed in 90-100% of the HNSCC cases and is considered an unfavourable prognostic marker. EGFR costitutive activation is linked with HNSCC pathogenesis.
Cetuximab is a monoclonal anti-EGFR antibody blocking the activation of the receptor and signal transduction. Cetuximab combined with radiotherapy is superior to radiotherapy only in the treatment of LA-HNSCC and is characterized by an acceptable toxicity profile.
RATIONALE:
A direct comparison between concomitant chemoradiotherapy with Cisplatin and the concomitant treatment with radiotherapy associated to cetuximab does not exist.
STUDY DESIGN:
Arm A: Radical radiotherapy (doses and volumes) concomitant with chemotherapy with Cisplatin (40 mg/mq/week) Arm B: Radical radiotherapy (doses and volumes) concomitant with therapy with the monoclonal antibody Cetuximab (400 mg/m2 ["loading dose"] and subsequently 250 mg /m2/week)
Study Overview
Status
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
Evaluation and comparison of the compliance of the two treatments;
SECONDARY OBJECTIVES:
Evaluation and comparison of the grade and incidence of acute toxicity; Evaluation and comparison of local control; Evaluation and comparison of event free survival (both local control and distant metastases); Evaluation and comparison of cause specific and overall survival.
INCLUSION/EXCLUSION CRITERIA
- Histologically confirmed squamous cell carcinoma (biopsy obtained from the tumor and/or from its lymphnodal metastases) originating from oral cavity, oropharynx, hypopharinx, supraglottic larynx;
- Locally advanced disease, defined by one of the following criteria: every T, N+, M0 ( T1, N1 cases excluded); T3-4, N0, M0;
- Not a nasopharynx, paranasal sinuses, salivary glands tumor;
- General conditions and concomitant diseases not considered a contraindication for chemotherapy or curative radiotherapy;
- No other surgical, chemotherapeutic or radiotherapic treatments for ENT region tumors or for tumors of other anatomical sites (with the exception of non-melanoma cutaneous tumors and of the carcinoma in situ of the uterine cervix and of other solid tumors whose primary treatment has been completed more than 3 years before the accrual in this study and never relapsed since primary treatment (the patient having been since then continuously disease- free);
- Availability for follow-up;
- Signed informed consent;
- An interval of maximum 3 weeks between staging procedures for local disease and randomization
- An interval of maximum 2 weeks between randomization and the onset of the treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Arezzo, Italy
- Radiotherapy Dept., Arezzo Hospital
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Brescia, Italy, 25100
- Radiotherapy Dept., Brescia University and Medical Oncology Dept., Brescia Hospital
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Firenze, Italy, 50100
- Radiotherapy Dept., Florence University
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Genoa, Italy
- Radiotherapy Dept., Genoa University
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Prato, Italy, 59100
- Radiotherapy Dept., Azienda USL 4 Prato
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Siena, Italy
- Radiotherapy Dept., Siena University
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Torino, Italy
- Radiotherapy Dept., Turin University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically confirmed squamous cell carcinoma (with biopsy on the primary and / or lymph node metastases) of the oral cavity, oropharynx, hypopharynx, larynx supraglottix;
- Locally advanced disease, defined by one of the following criteria: any T, N +, M0 (excluding T1, N1), T3-4, N0, M0;
- Not cancer nasopharynx or paranasal sinuses or salivary glands;
- General conditions and associated diseases which does not allow to perform chemotherapy or radiotherapy in a radical view;
- No other surgical treatments, chemotherapy or radiotherapy for cancer of head and neck or elsewhere, except non-melanoma skin cancer or in situ cervical cancer and other solid tumors for which radical treatment has been completed > three years prior to enrollment in the study and for which the patient has remained continuously free of disease;
- Accessibility to follow-up;
- Signing of informed consent;
- Interval between examinations of local staging and randomization, maximum 3 weeks
- Interval between randomization and initiation of treatment, maximum 2 weeks
Exclusion Criteria:
- Age <18 years
- ECOG performance status > 0-1
- Hemoglobin <9 g / dL
- Counts of granulocytes, total <1.5 x 10 ^ 9 / L
- Platelet count <100 x 10 ^ 9 / L
- Bilirubin> 1.5 times upper limit of normal (ULN)
- AST or ALT> 3 times ULN
- Creatinine clearance > 50 mL/min
- Mg > 0.5 mmol/L
- Pregnancy or lactation
- Presence of allergy to study drug or to the excipients used in their formulation
- Peripheral neuropathy ≥ grade 2 (CTCAE v3.0)
- Hearing loss / tinnitus ≥ grade 3 (CTCAE v3.0)
One of the following conditions:
- Myocardial infarction within 12 months prior to randomization
- Severe congestive heart failure
- Unstable angina
- Cardiomyopathy in act
- Ventricular arrhythmia
- uncontrolled hypertension
- Severe psychotic disorders in act
- Severe infection in act
- Any other serious illness that could interfere with the administration of the therapy provided by the protocol
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: cetuximab plus radiotherapy
Cetuximab given one week before radiotherapy (loading dose, 400 mg/m2) plus weekly (250 mg/m2), concomitant with radiotherapy (7O Gy on clinically involved sites).
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Other Names:
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Active Comparator: cisplatin plus radiotherapy
CDDP 40 mg/mq in a single weekly 1-hour infusion concomitant to radiotherapy: (70 Gy to clinically involved sites)
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Compliance
Time Frame: weekly during treatment
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Evaluation and comparison of the compliance of the two treatments arms
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weekly during treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
event free survival
Time Frame: bimonthly for two years, every 6 months thereafter
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Evaluation and comparison of the event free survival (both local control and distant metastases)
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bimonthly for two years, every 6 months thereafter
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acute toxicity
Time Frame: Weekly during treatment.
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Evaluation and comparison of the grade and incidence of acute toxicity.
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Weekly during treatment.
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Local control
Time Frame: bimonthly for two years after treatment, every six months thereafter
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Evaluation and comparison of local control
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bimonthly for two years after treatment, every six months thereafter
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cause specific survival
Time Frame: bimonthly after treatment for two years, then every 6 months
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Evualation and comparison of cause specific survival
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bimonthly after treatment for two years, then every 6 months
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overall survival
Time Frame: bimonthly after treatment for two years, then every 6 months
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evaluation and comperison of overall survival
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bimonthly after treatment for two years, then every 6 months
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Stefano M Magrini, Prof, Radiotherapy Dept., Brescia Hospital and Brescia University
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Otorhinolaryngologic Neoplasms
- Pharyngeal Diseases
- Stomatognathic Diseases
- Otorhinolaryngologic Diseases
- Mouth Diseases
- Laryngeal Diseases
- Neoplasms
- Head and Neck Neoplasms
- Mouth Neoplasms
- Laryngeal Neoplasms
- Pharyngeal Neoplasms
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Cisplatin
- Cetuximab
Other Study ID Numbers
- eudract 2010-021552-26
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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