Clinical trial NCT00999700: Induction Chemotherapy Followed by Cetuximab Plus Definitive Radiotherapy Versus Radiation Plus Cisplatin
Official title: Induction Chemotherapy Followed by Cetuximab Plus Definitive Radiotherapy Versus Radiation Plus Cisplatin
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Squamous Cell Carcinoma of the Head and Neck
Keywords: Locally advanced HNSCC
Chemo-radiation
Induction chemotherapy
Stage III/IV
Unresectable disease
Lead sponsor: Gruppo Oncologico del Nord-Ovest
Sponsor class: OTHER
First posted: 2009-10-22
Enrollment: 282
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Overall survival
timeFrame: 5 years
Secondary outcomes:
measure: Incidence of acute and late toxicities in the two arms
timeFrame: 5 years
measure: Progression free survival
timeFrame: 5 years
measure: Locoregional control
timeFrame: 5 years
measure: Response rate
timeFrame: 5 years
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: Ospedale Civile Ss. Antonio E Biagio
city: Aosta
country: Italy
facility: Ausl Della Valle D' Aosta
city: Bologna
country: Italy
facility: Policlinico S. Orsola-Malpighi
city: Cagliari
country: Italy
facility: Asl 8 - Ospedale Businco
city: Cuneo
country: Italy
facility: A.S.O. S. Croce E Carle
city: Genoa
country: Italy
facility: Irccs - Aou S. Martino - Oncology
city: Genoa
country: Italy
facility: Irccs - Aou San Martino - Radiotherapy
city: Genova
country: Italy
facility: Asl 3 Genovese
city: Genova
country: Italy
facility: E.O. Ospedali Galliera
city: Italy
country: Italy
facility: Azienda Ospedaliera Villa Scassi - Asl3
city: Milano
country: Italy
facility: Istituto Nazionale Dei Tumori
city: Modena
country: Italy
facility: Azienda Ospedaliero Universitaria Di Modena
city: Novi Ligure (al)
country: Italy
facility: Ospedale S. Giacomo
city: Parma
country: Italy
facility: Azienda Ospedaliero-Universitaria Di Parma
city: Pesaro
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti Di Fano
city: Reggio Emilia
country: Italy
facility: Arcispedale S. Maria Nuova
city: Rionero in Vulture (pz)
country: Italy
facility: Irccs Centro Di Riferimento Oncologico Di Basilicata (Crob)
city: Roma
country: Italy
facility: Ospedale S. Filippo Neri
city: Savona
country: Italy
facility: Ospedale S. Paolo
city: Turin
country: Italy
facility: A.O. Universitaria S. Giovanni Battista-Molinette Di Torino Torino (to)
city: Turin
country: Italy
facility: A.O. Universitaria S. Giovanni Battista-Molinette Di Torino
Study officials:
affiliation: ASCO, ESMO, AIOM, G.O.N.O.
name: MARCO MERLANO, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: - J.P. Pignon et al. Lancet 2000
citation: - A. Forastiere et al., New Engl J Med 2001
citation: - Adelstein DJ J.Clin.Oncol. 2003
citation: - Henke, New England 2004
citation: - J.A. Bonner et al., New Engl J Med 2006
citation: Merlano M. Alternating chemotherapy and radiotherapy in locally advanced head and neck cancer: an alternative? Oncologist. 2006 Feb;11(2):146-51. doi: 10.1634/theoncologist.11-2-146.
citation: - Posner M et al, New Engl J Med 2007
citation: - Vermorken J et al, New Engl J Med 2007
citation: - Lo Nigro, Journal of Cancer Research Clinical Oncology 2009
citation: Merlano M, Marchetti G. Radiochemotherapy in head and neck cancer. Cancer Treat Rev. 2003 Aug;29(4):291-6. doi: 10.1016/s0305-7372(03)00022-7.