Head and Neck Neoplasms, Laryngeal Neoplasms, Mouth Neoplasms, Pharyngeal Neoplasms
Conditions
Keywords
Head and Neck Cancer, Radiotherapy, Cetuximab, Cisplatin
Brief summary
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)
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
Interventions
DRUGcetuximab
* Cetuximab is given according to the standard mode of administration: loading dose : 400 mg/m2 one week before the start of radiotherapy (week -1), followed by a weekly dose of 250 mg/m2 during the weeks of the treatment with radiotherapy. * Radiotherapy: Doses: Clinical sites of disease (T e N) : total dose of 70 Gy given with a fractional dose of 2 Gy/day; prophylactic nodal volume (N) : total dose of 50 Gy given with a fractional dose of 2 Gy/day ; Treatment technique: conformal 3D. Intensity modulated radiotherapy (IMRT), also with simultaneous boost (SIB), is allowed.
DRUGcisplatin (associated to radiotherapy)
* CDDP dose: 40 mg/mq in a single weekly 1-hour infusion preceded by adequate hydration, diuretics e antiemetic premedication. * Radiotherapy: Doses: Clinical sites of disease (T e N) : total dose of 70 Gy given with a fractional dose of 2 Gy/day; prophylactic nodal volume (N) : total dose of 50 Gy given with a fractional dose of 2 Gy/day ; Treatment technique: conformal 3D. Intensity modulated radiotherapy (IMRT), also with simultaneous boost (SIB), is allowed.
Sponsors
Università degli Studi di Brescia
Azienda USL 4 Prato
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Compliance | weekly during treatment | Evaluation and comparison of the compliance of the two treatments arms |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| event free survival | bimonthly for two years, every 6 months thereafter | Evaluation and comparison of the event free survival (both local control and distant metastases) |
| acute toxicity | Weekly during treatment. | Evaluation and comparison of the grade and incidence of acute toxicity. |
| Local control | bimonthly for two years after treatment, every six months thereafter | Evaluation and comparison of local control |
| cause specific survival | bimonthly after treatment for two years, then every 6 months | Evualation and comparison of cause specific survival |
| overall survival | bimonthly after treatment for two years, then every 6 months | evaluation and comperison of overall survival |
Countries
Italy
Outcome results
None listed