Induction Chemotherapy Followed by Cetuximab Plus Definitive Radiotherapy Versus Radiation Plus Cisplatin

Phase 3

• Conditions: Squamous Cell Carcinoma of the Head and Neck
• Interventions: Drug: docetaxel - cisplatin - 5-fluorouracil; Drug: cisplatin; Radiation: radiotherapy; Drug: cetuximab

• Registration Number: NCT00999700
• Lead Sponsor: Gruppo Oncologico del Nord-Ovest

Brief Summary

A phase III trial of induction chemotherapy followed by definitive radiotherapy plus Cetuximab versus chemoradiation in unresectable, locally advanced, squamous cell carcinoma of the head and neck (HNC).

Detailed Description

The objective of this trial is to determine whether Cetuximab and radiation preceded by an induction chemotherapy, may be superior to an established chemoradiation program for HNC (RTOG regimen, Adelstein DJ J.Clin.Oncol. 2003;21:92-98).

Study Timeline

• Study Start: 2009-09
• Study First Submitted: 2009-10-16
• Study First Submitted QC: 2009-10-21
• Study First Posted: 2009-10-22
• Primary Completion: 2016-12-31
• Status Verified: 2017-09
• Last Update Submitted: 2017-09-01
• Last Update Posted: 2017-09-05
• Study Completion: 2021-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 282

Inclusion Criteria

• > 18 years of age
• Histologically or cytologically confirmed diagnosis of HNSCC
• Stage III/IV, not suitable for surgery (definitive cure rate improbable, technically unresectable or medical contraindication for surgery)
• At least one uni-dimensional measurable lesion either by CT scan or MRI
• Signed written informed consents prior to beginning protocol

Specific procedures:

• Tumor tissue available for immunohistochemical staining of EGFR expression and HPV
• Life expectancy of > 3 months at study entry
• ECOG Performance Status of <2 at study entry.
• Effective contraception if risk of conception exists.
• Neutrophils > 2.0/mm³, platelet count > 100,000/mm³, and hemoglobin > 10 g/dl
• Normal liver function
• Serum creatinine > 1.25 x ULN and/or creatinine clearance > 60 ml/min

Exclusion Criteria

• Prior systemic chemotherapy and/or radiotherapy
• Known peripheral neuropathy > grade 2 NCI-CTC version 3.0
• Known chronic heart failure
• Prior surgery, excluding prior diagnostic biopsy
• Known drug abuse
• Active uncontrolled infection
• Other concomitant anticancer therapy
• Distant metastasis
• Concurrent chronic systemic immune therapy, chemotherapy for disease other than cancer, or hormone therapy not indicated in the study protocol
• Clinically relevant coronary artery disease or history of a myocardial infarction within the last 12 months before study entry
• Medical or psychological condition that would not permit the patient to complete the trial or sign informed consent
• Nasopharyngeal carcinoma WHO type II or III
• Known allergic reaction against any of the components of the treatment
• Pregnancy (absence confirmed by beta-HCG test) or lactation period
• Any prior or on-going investigational medication
• Previous or current malignancy except basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ARM A	docetaxel - cisplatin - 5-fluorouracil	Induction chemotherapy: TCF (Vermorken, N Eng J Med 2007) Definitive treatment: RT + C-mab (Bonner, N Eng J Med 2006)
ARM B	cisplatin	RT + Cddp (RTOG, Adelstein, J Clin Oncol 2003)
ARM B	radiotherapy	RT + Cddp (RTOG, Adelstein, J Clin Oncol 2003)
ARM A	cetuximab	Induction chemotherapy: TCF (Vermorken, N Eng J Med 2007) Definitive treatment: RT + C-mab (Bonner, N Eng J Med 2006)
ARM A	radiotherapy	Induction chemotherapy: TCF (Vermorken, N Eng J Med 2007) Definitive treatment: RT + C-mab (Bonner, N Eng J Med 2006)

Primary Outcome Measures

Name	Time	Method
Overall survival	5 years

Secondary Outcome Measures

Name	Time	Method
Locoregional control	5 years
Progression free survival	5 years
Response rate	5 years
Incidence of acute and late toxicities in the two arms	5 years

Trial Locations

Locations (21)

Irccs - Aou S. Martino - Oncology; 🇮🇹 Genoa, Italy

Irccs - Aou San Martino - Radiotherapy; 🇮🇹 Genoa, Italy

E.O. Ospedali Galliera; 🇮🇹 Genova, Italy

Azienda Ospedaliero Universitaria Di Modena; 🇮🇹 Modena, Italy

Ausl Della Valle D' Aosta; 🇮🇹 Aosta, Italy

Ospedale Civile Ss. Antonio E Biagio; 🇮🇹 Alessandria, Italy

Policlinico S. Orsola-Malpighi; 🇮🇹 Bologna, Italy

Asl 8 - Ospedale Businco; 🇮🇹 Cagliari, Italy

A.S.O. S. Croce E Carle; 🇮🇹 Cuneo, Italy

Asl 3 Genovese; 🇮🇹 Genova, Italy

Azienda Ospedaliera Villa Scassi - Asl3; 🇮🇹 Italy, Italy

Istituto Nazionale Dei Tumori; 🇮🇹 Milano, Italy

Ospedale S. Giacomo; 🇮🇹 Novi Ligure (al), Italy

Azienda Ospedaliero-Universitaria Di Parma; 🇮🇹 Parma, Italy

Azienda Ospedaliera Ospedali Riuniti Di Fano; 🇮🇹 Pesaro, Italy

Arcispedale S. Maria Nuova; 🇮🇹 Reggio Emilia, Italy

Irccs Centro Di Riferimento Oncologico Di Basilicata (Crob); 🇮🇹 Rionero in Vulture (pz), Italy

Ospedale S. Filippo Neri; 🇮🇹 Roma, Italy

A.O. Universitaria S. Giovanni Battista-Molinette Di Torino Torino (to); 🇮🇹 Turin, Italy

Ospedale S. Paolo; 🇮🇹 Savona, Italy

A.O. Universitaria S. Giovanni Battista-Molinette Di Torino; 🇮🇹 Turin, Italy