Clinical trial NCT00251381: Cetuximab & Concomitant-Boost Accelerated RT in Patients With Locally Advanced Oropharynx Squamous Cell Carcinoma.
Official title: Open Label Randomized Phase II, Multicentre, Pilot Study to Evaluate Safety and Efficacy of the Combination of Cetuximab and Concomitant-Boost Accelerated Radiotherapy Followed or Not by a Complementary Treatment With Cetuximab in Patients With Locally Advanced Oropharynx Squamous Cell Carcinoma.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Oropharyngeal Neoplasms
Keywords: Oropharyngeal Neoplasms
Cetuximab
Concomitant-boost accelerated radiotherapy
Lead sponsor: Trial Form Support S.L.
Sponsor class: OTHER
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2005-11-10
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the 1-year rate of locoregional disease control in the experimental arm, using a control arm to avoid selection bias.

Detailed description: * To determine the 1-year rate of locoregional disease control in the experimental arm, using a control arm to avoid selection bias.
* To determine the 2 and 3 year rate of locoregional disease control.
* To evaluate the safety and toxicity of the combination of cetuximab and concomitant-boost accelerated radiotherapy followed by 12 weeks of complementary treatment with cetuximab. Both acute and chronic toxicity will be assessed.
* To determine specific disease-free survival, event-free survival, disease-specific survival and overall survival
* To determine acute and late toxicity
* To determine EGFR, p53, Ki67, and evaluate its value as a prognostic factor.

Eligibility criteria: Inclusion Criteria:

* Written informed consent.
* Aged between 18 and 80, inclusive.
* Karnofsky functional status \>= 70% at the time of enrolment in study.
* Life expectancy of more than 3 months.
* Histologically confirmed diagnosis of oropharyngeal squamous cell carcinoma: base of tongue, vallecula, tonsil and tonsillar fossa and pillars, glossotonsillar sulcus, inferior surface of the soft palate, uvula and lateral and posterior oropharyngeal wall.
* Stage III or IV with no evidence of distant metastasis (IVA or IV B)
* Patients in medical conditions to receive a radical concomitant-boost accelerated radiotherapy treatment.
* Neutrophils \>= 1500/ mm3, platelet count \>= 100 000/ mm3 and haemoglobin \>= 10 g/ dL.
* Proper liver function: total bilirubin \<= 1.5 x upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<= 2.5 x ULN.
* Proper renal function: serum creatinine \<= 1.5 x ULN; if the values are \> 1.5 x ULN, creatinine clearance should be \>= 55 ml/min.
* Serum calcium within normal limits.
* Adequate nutritional state: weight loss \< 20% with respect to usual weight and serum albumin \> 35 g/l.
* Effective birth control method if there is possibility of conception and/or pregnancy.
* Availability of tumour tissue for immunohistochemical analysis of EGFR expression.

Exclusion Criteria:

* Metastatic disease.
* Previous surgical, radiotherapy and/or chemotherapy treatment for the disease in the study.
* Other non-oropharyngeal tumour sites in the head and neck area.
* Other previous and/or simultaneous squamous cell carcinoma.
* Diagnosis of any other cancer in the previous 5 years, except properly treated carcinoma in situ of the uterine cervix and/or basal cell skin carcinoma.
* Active infection (infection requiring intravenous antibiotics), including active tuberculosis and diagnosed HIV.
* Uncontrolled hypertension defined as systolic blood pressure \>= 180 mm Hg and/or diastolic blood pressure \>= 130 mm Hg at rest.
* Pregnancy (absence of pregnancy must be confirmed with the serum-HCG test) or breast-feeding women.
* Chronic, concomitant systemic immunotherapy, or hormonal treatment for the cancer.
* Other concomitant anti-cancer treatments.
* Clinically significant coronary artery disease, history of myocardial infarction in the previous 12 months or high risk of out of control arrhythmia or cardiac insufficiency.
* Chronic obstructive pulmonary disease which may have required \> 3 hospitalisations in the previous 12 months.
* Out of control active peptic ulcer.
* Presence of a psychological or medical illness which might impede the patient from carrying out the study or giving his or her signature on the informed consent
* Known drug abuse (with the exception of excessive alcohol consumption)
* Known allergic reaction to any of the components of the treatment to be studied.
* Previous treatment with monoclonal antibodies or signal transduction inhibitors or other EGFR-targeted treatment.
* Any experimental treatment in the 30 days prior to enrolment in the study.

Primary outcomes:
measure: 1-year rate of Locoregional Disease Control in the experimental arm, deffined as complete and persistent disappearance of disease in the primary tumour and regional lymph nodes.
Secondary outcomes:
measure: Toxicity and safety of treatment will be evaluated using the Common Toxicity Criteria (CTC) of the NCI, version 3.0.; and late toxicity from radiotherapy, using RTOG/EORTC Late Radiation Morbidity Scoring Scheme.
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Germans Tries i Pujol
state: Barcelona
city: Hospitalet de Llobregat
country: Spain
facility: Institut Catala Oncologia: Hospital Duran y Reynals
state: Barcelona
city: A Coruna
country: Spain
facility: Centro Oncológico Regional de Galicia
state: Coruña
city: El Palmar
country: Spain
facility: H.U. Virgen de la Arrixaca
state: Murcia
city: Pamplona
country: Spain
facility: Hospital de Navarra
state: Navarra
city: Santa Cruz de Tenerife
country: Spain
facility: H. U. de Canarias
state: Sta Cruz de Tenerife
city: Barcelona
country: Spain
facility: H. del Mar / H. de la Esperanza
city: Barcelona
country: Spain
facility: H. de la Santa Creu I Sant Pau
city: Girona
country: Spain
facility: H. Josep Trueta (ICO)
city: Las Palmas de Gran Canaria
country: Spain
facility: H. G. Doctor Negrín
city: Madrid
country: Spain
facility: Clinica Ruber Internacional
city: Madrid
country: Spain
facility: H. Ramón y Cajal
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: H. Gregorio Marañón
city: Malaga
country: Spain
facility: Complejo Hospitalario Virgen de la Victoria
city: Malaga
country: Spain
facility: H. Carlos Haya
city: Santiago
country: Spain
facility: H.U. de Santiago
city: Vigo
country: Spain
facility: H. do Meixoeiro
Study officials:
affiliation: Institut Catala Oncologia: Hospital Durán y Reynals
name: Ricard Mesia, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut Catala Oncologia: Hospital Durán y Reynals
name: Joaquin Gomez, MD
role: PRINCIPAL_INVESTIGATOR
References: