Clinical trial NCT01427478: Evaluation of Afatinib in Maintenance Therapy in Squamous Cell Carcinoma of the Head and Neck
Official title: A Randomized, Double-blind, Placebo-controlled Phase III Study, to Evaluate the Efficacy of Afatinib (BIBW2992) in Maintenance Therapy After Post- Operative Radio-chemotherapy in Squamous-cell Carcinoma of the Head and Neck: GORTEC 2010-02
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Head and Neck Squamous Cell Carcinoma
Keywords: Head and neck squamous cell carcinoma
Post operative radio-chemotherapy
Randomisation
Maintenance treatment
Afatinib
Lead sponsor: Centre Leon Berard
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
First posted: 2011-09-01
Enrollment: 134
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: The purpose of this study is to evaluate the efficacy and safety of Afatinib in maintenance therapy after post-operative radiochemotherapy (66 Gy and Cisplatin at the dose of 100mg/m2 every 3 weeks)in squamous cell carcinoma of the head and neck.

Detailed description: The reference treatment for operated squamous cell carcinoma of the head and the neck is a radiochemotherapy with Cisplatin (in the dose of intravenous 100 mg / m2 IV) every 3 weeks).

The Receptor of EGFR (Epidermal Growth Factor) or REGF is a membrane receptor; it's activation leads the cellular growth and inhibits apoptotic capacities. This receptor is overexpressed in numerous solid tumors, including ENT tumors. Several clinical studies showed that an over expression of the REGF in ENT tumors was a dominant factor of poor prognostic.

Afatinib (BIBW2992) is a strong and irreversible inhibitor of the EGFR ( type 1 human epidermic growth factor receptor, also known as HER1) and of the HER2 (human epidermal growth factor receptor 2).

Currently, 3 phase III clinical studies in postoperative situation and using an anti-REGF are in progress: 2 in concomitant situation with the radiotherapy and 1 both in concomitance and in adjuvant therapy with radiotherapy.

The preliminary results of a phase II study show that Afatinib is efficient in patients with local or metastatic relapse of a squamous cell carcinoma of the sphere ENT after a first line with Cisplatin and its tolerance is correct.

These data lead us to propose in post-operative situation, in patients with a squamous cell carcinoma of the head and neck, a radiochemotherapy with Cisplatin followed by a treatment of maintenance by Afatinib or by placebo.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Histologically-confirmed diagnosis of non metastatic squamous-cell carcinoma of oral cavity ; oropharynx, larynx or hypopharynx.
* Macroscopically complete resection of disease.
* High-risk histological features defined as :

Microscopically incomplete tumour resection and/or invasion of regional lymph nodes with extracapsular extension (pN+R+)

* Indication of radio-chemotherapy (at least 60 Gy of radiotherapy and at least 2 cycles of chemotherapy)
* Start of radio-chemotherapy within 8 weeks after surgery
* Performance Status (PS) ECOG \<= 2
* Adequate Blood tests, renal and liver functions in the 15 days prior inclusion defined as :

Hemoglobin \> 9 g/dL Neutrophil count \> 1500 x 109/L Platelets \> 100 x 109/L Total bilirubin \< 1,5x upper limit of normal (ULN) SGOT and SGPT \< 2,5 x ULN Alkaline Phosphatase \< 2,5 xULN Serum creatinine \< 110 µmol/L or creatinine clearance \> 55 ml/min (estimated by Cockcroft Formula) Absence of proteinuria

* Women of childbearing age must use adequate means of contraception(oral hormon contraceptive, intrauterine contraceptive device, double barrier method of contraception).
* Mandatory affiliation with a healthy security insurance.
* Dated and signed written informed consent.

Exclusion Criteria:

* Macroscopic residual tumour after resection(R2)
* Metastatic disease
* Prior treatment for Head and neck cancer with chemotherapy, radiotherapy or any cancer target therapy
* Prior or concomitant malignancies (except for basal cell skin cancer ; in situ cervical carcinoma or other malignancies with a complete response \> 5 years)
* History of heavy hypersensibility reaction to Cisplatin
* Uncontrolled pulmonary, cardiac , hepatic or renal disease.
* History of interstitial pneumopathy
* Significant cardiovascular disease :

Congestive cardiac failure\> New York Heart Association (NYHA) Class II Myocardial infraction within 6 months prior to inclusion Unstable angina Severe cardiac arrythmia Uncontrolled hypertension while receiving appropriate medication (≥ 160 mm Hg systolic and/or ≥ 90 mm Hg diastolic) Disorder of left ventricular function with ejection fraction \< 50% Severe cerebrovascular accident within 6 months prior to inclusion History of severe thromboembolism within 6 months prior to inclusion Cardiovascular baseline QTcB \>480 ms (Calculated with Bazett Formula) Bradycardia Electrolytic disorders

- Hepatic affection like : hepatitis B or C chronic advanced decompensated hepatitis hepatitic cirrhosis or newly treated chronic hepatitis or nowadays treated with immunosuppressive drugs severe auto-immune hepatitis or disease

* HIV known history
* Recent digestive symptoms with diarrhea as :

Crohn's disease malabsorption syndrome diarrhea Grade CTC ≥ 2

* Active drug or alcohol use or dependence
* Pregnant or breast-feeding women , or no use of effective birth control methods for women of childbearing potential, , or men who don't accept to use an effective birth control methods during the study
* Impossible follow-up

Primary outcomes:
measure: Disease Free Survival 2 years after the end of radiotherapy
timeFrame: 2 years after the end of radiotherapy
Secondary outcomes:
measure: Safety profile
timeFrame: Every 28 days during the maintenance therapy,every 2 months during 1 year after maintenance therapy; and every 3 months during the following 3 years
measure: Quality of life of patient, evaluated by questionnary
timeFrame: Baseline; at the end of radiotherapy, at 1 and 2 years after the beginning of maintenance treatment
measure: Overall Survival (OS)
timeFrame: Death
Other outcomes:
Locations:
city: Angers
country: France
facility: Centre Paul Papin
city: Avignon
country: France
facility: Institut Sainte-Catherine
city: Bordeaux
country: France
facility: CHU Bordeaux - Hôpital Saint-André
city: Bordeaux
country: France
facility: Polyclinique de Bordeaux Nord
city: Brest
country: France
facility: CHRU Brest - Hôpital Morvan
city: Caen
country: France
facility: Centre François Baclesse
city: Créteil
country: France
facility: CHIC Créteil
city: Le Havre
country: France
facility: Centre Guillaume le Conquérant
city: Lorient
country: France
facility: Centre Hospitalier Bretagne Sud
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: AP-HM La Timone Adultes
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Poitiers
country: France
facility: CHU Poitiers
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Priest en Jarez
country: France
facility: Institut de Cancérologie de la Loire
city: Saint-Herblain
country: France
facility: Institut de Cancérologie de l'Ouest
city: Saint-Nazaire
country: France
facility: Pôle Hospitalier Mutualiste- Centre Etienne Dolet
city: Strasbourg
country: France
facility: Strasbourg Oncologie Libérale
city: Thonon-les-bains
country: France
facility: Hopitaux du Léman
city: Toulouse
country: France
facility: Clinique Pasteur Bâtiment l'Atrium
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Tours
country: France
facility: CHU TOURS (Hôpital Bretonneau)
city: Valence
country: France
facility: Centre de Radiothérapie Marie Curie
city: Vandoeuvre-les-Nancy
country: France
facility: Institut de Cancérologie de lorraine (ICL)
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Centre Léon Bérard; Lyon
name: Séverine RACADOT, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Léon Bérard , Lyon
name: Pascal POMMIER, MD
role: PRINCIPAL_INVESTIGATOR
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