Accelerated Modulated Fractionation (SIB-IMRT) for Head and Neck District

NCT03001570 | Unknown Phase 2

• 1 other identifier: European Institute of Oncology
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Nowadays the association between radiotherapy and the anti- Epidermal Growth Factor Receptor (anti-EGFR) monoclonal antibody Cetuximab represents a valid option in the treatment of head and neck locally advanced squamous neoplasm and, particularly, of oropharynx carcinoma. Up to date we have only indirect comparison with the standard curative treatment (i.e. concurrent radiochemotherapy) and the preliminary data show equivalent efficacy of both regimens. For this reason, concurrent Cetuximab and radiotherapy is administered in patients not eligible to chemoradiotherapy. The introduction of Cetuximab has been associated to new kind of toxicities, especially cutaneous, that have increasingly reported. The aim of our study is to improve the toxicity/benefit ratio in patients receiving concurrent radiotherapy and cetuximab for locally advanced head and neck neoplasm. Hence, this improvement could be achieved by modulating radiation therapy dose per fraction following Cetuximab pharmacokinetics.

Conditions

Carcinoma of the Head and Neck

Outcome Measures

Primary Outcomes (1)

• Number of patients who experienced acute toxicity with Grade 3 or Grade 4 adverse events according to Scala CTCAE v4.0 toxicity criteria and scale Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer (RTOG / EORTC)

  During radiotherapy, patients will be assessed weekly for acute toxicity using validated international scales.acute toxicity will be assessed with CTCAE V 4.03 (Common Terminology Criteria of Adverse Events Version 4.03) scale. Furthermore pain (NRS pain scale) nutritional assessment (weight in kilograms ) will be performed.

  up to 7 days during RT treatment

Secondary Outcomes (2)

• Number of patients who experienced late toxicity with Grade 3 or Grade 4 adverse events according to Scala CTCAE v4.0 toxicity criteria and scale RTOG / EORTC

  up to 6-8 weeks after treatment completion and then up to 2 years

• Number of patients who experienced local or distance recurrence of disease assessed through clinical and radiological controls

  up to 6-8 weeks after treatment completion and then up to 2 years

Study Arms (1)

Arm 1

EXPERIMENTAL

Radiotherapy treatment associated with concurrent Cetuximab administration. Patients candidate to curative concurrent Cetuximab and Radiotherapy are eligible for this study. After expressing written informed consent, patients will perform CT simulation. Then an IMRT-SIB (Simultaneous Integrated Boost) treatment plan will be elaborated and deliver the following Cetuximab pharmacokinetic: Length: 6 weeks; 1 fraction daily (From Monday to Friday) 30 Total Fractions (5 per week, 6 weeks of treatment). Cetuximab will be administered weekly from a week before starting radiotherapy until the end of treatment for 7 subsequent administration accordingly to the standard schedule (1 before and 6 during radiotherapy).

Drug: Cetuximab plus Radiotherapy

Interventions

Cetuximab plus Radiotherapy DRUG

Standard dose of a curative radiotherapy treatment is 70Gy given with conventional fractionation (2G daily) in an overall length of 7 weeks. In this study, the fractionation has been modified accordingly Cetuximab pharmacokinetics. Cetuximab will be administered with standard schedule: charge dose of 400mg/mq a week before the beginning of concurrent treatment, then weekly doses of 250mg/mq intravenous for 7 administration. This schedule to obtain the same biological efficacy on tumour with lower toxicity on healthy tissues.

Also known as: Radiotherapy, IMRT

Arm 1

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histological proof of locally advanced squamous carcinoma of oropharynx, larynx, hypopharynx (stage III and Iva)
• Overexpression of EGFR (\>50%)
• Patients previously considered non-eligible for curative radio-chemotherapy for clinical reasons.
• Performance Status (ECOG) ≤ 2
• Age ≥ 18 years
• Possibility of correct administration of treatment
• Written informed consent

You may not qualify if:

• Distant metastases
• Oral cavity or rhinopharynx neoplasm
• Need of cutaneous bolus
• Previous treatments on head and neck district
• Collagenopathies or other severe systemic disease
• Severe cardiopathies or myocardial infarction in the previous 12 months, serious hepatopathies or other diseases with heavy impact on general conditions.
• Psychiatric disorders or other conditions preventing from expressing informed consent.

Sponsors & Collaborators

• European Institute of Oncology: lead

Study Sites (1)

Division of Radiotherapy European Institute of Oncology

Milan, MI, 20141, Italy

RECRUITING

MeSH Terms

Interventions

Cetuximab; Radiotherapy; Radiotherapy, Intensity-Modulated

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted

Study Officials

• Roberto Orecchia, Prof

  European Institute of Oncology

  STUDY DIRECTOR

Central Study Contacts

Roberto Orecchia, Prof.

CONTACT

roberto.orecchia@ieo.it

Daniela Alterio, MD

CONTACT

daniela.alterio@ieo.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2016
• First Posted: December 23, 2016
• Study Start: January 1, 2014
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2023
• Last Updated: June 28, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)