Cetuximab & Concomitant-Boost Accelerated RT in Patients With Locally Advanced Oropharynx Squamous Cell Carcinoma.

Overview

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.

Full Title of Study: “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

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Treatment
  • Masking: None (Open Label)

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.

Interventions

• Drug: Cetuximab

Clinical Trial Outcome Measures

Primary Measures

• 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 Measures

• 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.

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Trial Form Support S.L.
• Collaborator
  • Merck KGaA, Darmstadt, Germany
• Overall Official(s)
  • Ricard Mesia, MD, Principal Investigator, Institut Catala Oncologia: Hospital Durán y Reynals
  • Joaquin Gomez, MD, Principal Investigator, Institut Catala Oncologia: Hospital Durán y Reynals
• Overall Contact(s)
  • Jaume Graupera, 34 93 185 02 00, jaume.graupera@trialformsupport.com