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Evaluation of Afatinib in Maintenance Therapy in Squamous Cell Carcinoma of the Head and Neck (BIBW2992ORL)

This study is currently recruiting participants.
Verified March 2013 by Centre Leon Berard
Sponsor:
Collaborator:
Boehringer Ingelheim Pharmaceuticals
Information provided by (Responsible Party):
Centre Leon Berard
ClinicalTrials.gov Identifier:
NCT01427478
First received: August 31, 2011
Last updated: March 1, 2013
Last verified: March 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Head and Neck Squamous Cell Carcinoma
 Drug: AFATINIB
Drug: Placebo of AFATINIB
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Further study details as provided by Centre Leon Berard:

Primary Outcome Measures:
  • Disease Free Survival 2 years after the end of radiotherapy [ Time Frame: 2 years after the end of radiotherapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety profile [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
    Safety profile is characterized by type; frequency and seriousness of the toxicities showed by the patients and graded using CTCAE - V04

  • Quality of life [ Time Frame: Baseline; at the end of radiotherapy, at 1 and 2 years after the beginning of maintenance treatment ] [ Designated as safety issue: No ]
    Quality of life will be evaluated at baseline; at the end of radiotherapy and also at 1 and 2 years after the beginning of maintenance treatment. The EORTC's questionnaire QLQ-C30 and the additional module " Head and neck " QLQ-H&N35 will be used.

  • Overall Survival (OS) [ Time Frame: Death ] [ Designated as safety issue: No ]
    OS is the time from randomization to the date of death due to any cause or date of the last news.


Estimated Enrollment: 315
Study Start Date: September 2011
Estimated Study Completion Date: September 2019
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AFATINIB
Radiotherapy combined with a chemotherapy by Cisplatin IV at the dose of 100mg/m2 every 3 weeks, followed by a maintenance therapy with BIBW 2992 for 1 year at the dose of 40 mg/during the 1st month and then 50 mg/d during the 11 following months
 Drug: AFATINIB
AFATINIBat the dose of 40 mg/during the 1st month and then 50 mg/d during the 11 following months
Other Name: BIBW 2992
Placebo Comparator: PLACEBO
Radiotherapy associated with a chemotherapy by Cisplatin IV at the dose of 100mg/m2 every 3 weeks, followed by a maintenance therapy with placebo of BIBW 2992 for 1 year at the dose of 40 mg/during the 1st month and then 50 mg/d during the 11 following months
 Drug: Placebo of AFATINIB
placebo of Afatinib at the dose of 40 mg/during the 1st month and then 50 mg/d during the 11 following months
Other Name: Placebo of BIBW 2992

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01427478

Contacts
Contact: Sophie DUSSART, MD +33478782752 dussart@lyon.fnclcc.fr

Locations
France
Centre Paul Papin Recruiting
Angers, France, 49933
Principal Investigator: Claude TUCHAIS, MD            
Sub-Investigator: Sandrine Brigitte VINCHON-PETIT, MD            
Sub-Investigator: Eric JADAUD, MD            
Sub-Investigator: Philippe MAILLART, MD            
Sub-Investigator: Olivier Joseph CAPITAIN, MD            
Sub-Investigator: Benjamin LINOT, MD            
Sub-Investigator: Lysian CARTIER, MD            
Institut Sainte-Catherine Recruiting
Avignon, France, 84000
Principal Investigator: Marc ALFONSI, MD            
Sub-Investigator: Werner HILGERS, MD            
Sub-Investigator: Sabine WALTER, MD            
Sub-Investigator: Julien GRENIER, MD            
Sub-Investigator: Frédéric PLAT, MD            
Sub-Investigator: Sylvie KIRSCHER, MD            
Polyclinique de Bordeaux Nord Recruiting
Bordeaux, France, 33300
Principal Investigator: François GUICHARD, MD            
Sub-Investigator: Olivier DAHAN, MD            
CHU Bordeaux - Hôpital Saint-André Recruiting
Bordeaux, France, 33075
Principal Investigator: Laurence DIGUE, MD            
Sub-Investigator: Alain RAVAUD, PhD            
Principal Investigator: Marine GROSS-GOUPIL, MD            
Sub-Investigator: Denis SMITH, MD            
Sub-Investigator: Sophie ROCA THERONDEL, MD            
Sub-Investigator: Nathalie TRUFFLANDIER, MD            
Sub-Investigator: Hélène DEMEAUX, MD            
Centre François Baclesse Recruiting
Caen, France, 14076
Principal Investigator: Dominique De RAUCOURT, MD            
Sub-Investigator: Jean-Pierre RAME, MD            
Sub-Investigator: Radj GERVAIS, MD            
Sub-Investigator: Bernard GERY, MD            
Sub-Investigator: Marie-Yolande LOUIS, MD            
Sub-Investigator: Carmen-Mihaela FLORESCU, MD            
Centre Jean Perrin Recruiting
Clermont-Ferrand, France, 63011
Principal Investigator: Anne-Françoise DILLIES, MD            
Sub-Investigator: Michel LAPEYRE, MD            
CHIC Créteil Recruiting
Créteil, France, 94010
Principal Investigator: Michel MARTIN, MD            
Sub-Investigator: Emmanuelle MALAURIE, MD            
Sub-Investigator: Isabelle EKOUME, MD            
Sub-Investigator: Stéphane HENAULT, MD            
Centre Guillaume le Conquérant Recruiting
Le Havre, France, 76600
Principal Investigator: Laurent MARTIN, MD            
Centre Hospitalier Bretagne Sud Recruiting
Lorient, France, 56100
Principal Investigator: Christian SIRE, MD            
Sub-Investigator: régine LAMY, MD            
Sub-Investigator: Isabelle CUMIN, MD            
Sub-Investigator: Joelle EGRETEAU, MD            
Centre Léon Bérard Recruiting
Lyon, France, 69373
Contact: Sophie DUSSART, MD            
Principal Investigator: Séverine RACADOT, MD            
Sub-Investigator: Pascal POMMIER, MD            
Sub-Investigator: Xavier MONTBARBON, MD            
Sub-Investigator: Jerome FAYETTE, MD            
Sub-Investigator: Violaine BENEYTON, MD            
Sub-Investigator: Cecile LAUDE, MD            
Centre Antoine Lacassagne Recruiting
Nice, France, 06189
Principal Investigator: Frédéric PEYRADE, MD            
Sub-Investigator: Juliette THARIAT, MD            
Sub-Investigator: Olivier DASSONVILLE, MD            
Sub-Investigator: Gilles POISSONNET, MD            
Sub-Investigator: Alexandre BOZEC, MD            
Sub-Investigator: Christophe HEBERT, MD            
Sub-Investigator: Véronique MARI, MD            
Sub-Investigator: Marie-Eve CHAND-FOUCHE, MD            
Centre Hospitalier Lyon Sud Not yet recruiting
Pierre-Bénite, France, 69310
Principal Investigator: Véronique FAVREL, MD            
CHU Poitiers Recruiting
Poitiers, France, 86021
Principal Investigator: Jean-Marc TOURANI, PhD            
Sub-Investigator: Karine MOUMOUH, MD            
Centre Eugène Marquis Recruiting
Rennes, France, 44229
Principal Investigator: Elodie VAULEON, MD            
Sub-Investigator: Brigitte LAGUERRE, MD            
Centre Henri Becquerel Recruiting
Rouen, France, 76038
Principal Investigator: Isabelle TENNEVET, MD            
Sub-Investigator: Cristian MOLDOVAN, MD            
Sub-Investigator: Hugues AUVRAY, MD            
Sub-Investigator: Leila ADRIOUCH, MD            
Sub-Investigator: Cristina Ramona ALEXANDRU, MD            
Sub-Investigator: Florian CLATOT, MD            
Sub-Investigator: Ovidiu VERESEZAN, MD            
Institut de Cancérologie de la Loire Recruiting
Saint Priest en Jarez, France, 42270
Principal Investigator: Pierre FOURNEL, MD            
Sub-Investigator: Nicolas MAGNE, MD            
Sub-Investigator: Thierry MURON, MD            
Institut de Cancérologie de l'Ouest Recruiting
Saint-Herblain, France, 44805
Principal Investigator: Frederic ROLLAND, MD            
Sub-Investigator: Emmanuelle BOMPAS, MD            
Sub-Investigator: Etienne BARDET, MD            
Sub-Investigator: Franck DROUET, MD            
Sub-Investigator: Damien VANSTEENE, MD            
Pôle Hospitalier Mutualiste- Centre Etienne Dolet Recruiting
Saint-Nazaire, France, 44600
Principal Investigator: Isabelle BARTHOLOMOT-FORGEOT, MD            
Sub-Investigator: Philippe BERGEROT, MD            
Sub-Investigator: Valérie DELECROIX, MD            
Sub-Investigator: Philippe DEGUIRAL, MD            
Sub-Investigator: Catherine LIGEZA, MD            
Sub-Investigator: Thierry CHATELLIER, MD            
Sub-Investigator: Evelyne TAMBY, MD            
Clinique Pasteur Bâtiment l'Atrium Recruiting
Toulouse, France, 31076
Principal Investigator: Olivier GALOCHER, MD            
Sub-Investigator: Catherine MELLE, MD            
Sub-Investigator: Christian CHEVELLE, MD            
Sub-Investigator: Philippe DUDOUET, MD            
Sub-Investigator: Gaelle JIMENEZ, MD            
Institut Claudius Regaud Recruiting
Toulouse, France, 71000
Principal Investigator: Michel RIVES, MD            
Sub-Investigator: Anne LAPRIE, MD            
Sub-Investigator: Jean-Pierre DELORS, MD            
Sub-Investigator: Sabrina BOYRIE, MD            
Sub-Investigator: Nathalie CAUNES, MD            
Sub-Investigator: Anne DUCASSOU, MD            
CHU TOURS (Hôpital Bretonneau) Recruiting
Tours, France, 37044
Principal Investigator: Gilles CALAIS, MD            
Sub-Investigator: Sophie CHAPET, MD            
Sub-Investigator: Amandine LOUBIERE, MD            
Centre de Radiothérapie Marie Curie Recruiting
Valence, France, 26000
Principal Investigator: Mathieu BOSSET, MD            
Sub-Investigator: Mohammed El-Hedi ZOUAI, MD            
Sub-Investigator: Sébastien CLIPPE, MD            
Sub-Investigator: Bertrand FLEURY, MD            
Institut Gustave Roussy Recruiting
Villejuif, France, 94805
Principal Investigator: Jean BOURHIS, MD            
Sub-Investigator: Nicolas DALY-SCHVEITZER, MD            
Sub-Investigator: Yungan TAO, MD            
Sub-Investigator: Pierre BLANCHARD, MD            
Sub-Investigator: Stéphane TEMAM, MD            
Sponsors and Collaborators
Centre Leon Berard
Boehringer Ingelheim Pharmaceuticals
Investigators
Principal Investigator: Séverine RACADOT, MD Centre Léon Bérard; Lyon
Principal Investigator: Pascal POMMIER, MD Centre Léon Bérard , Lyon
  More Information

Publications:

Responsible Party: Centre Leon Berard
ClinicalTrials.gov Identifier: NCT01427478     History of Changes
Other Study ID Numbers: BIBW2992 ORL, 2010-023265-22
Study First Received: August 31, 2011
Last Updated: March 1, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Centre Leon Berard:
Head and neck squamous cell carcinoma
Post operative radio-chemotherapy
Randomisation
Maintenance treatment
Afatinib

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
 Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site

ClinicalTrials.gov processed this record on May 22, 2013