Evaluation of Afatinib in Maintenance Therapy in Squamous Cell Carcinoma of the Head and Neck
NCT ID: NCT01427478
Last Updated: 2021-06-01
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE3
134 participants
INTERVENTIONAL
2011-09-30
2021-05-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
LUX-Head & Neck 4: Afatinib (BIBW 2992) Versus Placebo for the Treatment of Head and Neck Squamous Cell Cancer After Treatment With Chemo-radiotherapy
NCT02131155
LUX-Head&Neck 3: Afatinib (BIBW2992) Versus Methotrexate for the Treatment of Recurrent and/or Metastatic Head and Neck Squamous Cell Cancer After Platinum Based Chemotherapy
NCT01856478
LUX-Head&Neck 2: A Phase III Trial of Afatinib (BIBW 2992) Versus Placebo for the Treatment of Head and Neck Squamous Cell Cancer After Treatment With Chemo-radiotherapy
NCT01345669
LUX-Head&Neck 1: A Phase III Trial of Afatinib (BIBW2992) Versus Methotrexate for the Treatment of Recurrent and/or Metastatic (R/M) Head and Neck Squamous Cell Cancer After Platinum Based Chemotherapy
NCT01345682
Afatinib After Chemoradiation and Surgery in Treating Patients With Stage III-IV Squamous Cell Carcinoma of the Head and Neck at High-Risk of Recurrence
NCT01824823
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
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
AFATINIB
AFATINIBat the dose of 40 mg/during the 1st month and then 50 mg/d during the 11 following months
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
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
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
AFATINIB
AFATINIBat the dose of 40 mg/during the 1st month and then 50 mg/d during the 11 following months
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 Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Boehringer Ingelheim
INDUSTRY
Centre Leon Berard
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Séverine RACADOT, MD
Role: PRINCIPAL_INVESTIGATOR
Centre Léon Bérard, Lyon
Pascal POMMIER, MD
Role: PRINCIPAL_INVESTIGATOR
Centre Léon Bérard, Lyon
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Centre Paul Papin
Angers, , France
Institut Sainte-Catherine
Avignon, , France
CHU Bordeaux - Hôpital Saint-André
Bordeaux, , France
Polyclinique de Bordeaux Nord
Bordeaux, , France
CHRU Brest - Hôpital Morvan
Brest, , France
Centre François Baclesse
Caen, , France
CHIC Créteil
Créteil, , France
Centre Guillaume le Conquérant
Le Havre, , France
Centre Hospitalier Bretagne Sud
Lorient, , France
Centre Léon Bérard
Lyon, , France
AP-HM La Timone Adultes
Marseille, , France
Centre Antoine Lacassagne
Nice, , France
CHU Poitiers
Poitiers, , France
Centre Eugène Marquis
Rennes, , France
Centre Henri Becquerel
Rouen, , France
Institut de Cancérologie de l'Ouest
Saint-Herblain, , France
Pôle Hospitalier Mutualiste- Centre Etienne Dolet
Saint-Nazaire, , France
Institut de Cancérologie de la Loire
Saint-Priest-en-Jarez, , France
Strasbourg Oncologie Libérale
Strasbourg, , France
Hopitaux du Léman
Thonon-les-Bains, , France
Clinique Pasteur Bâtiment l'Atrium
Toulouse, , France
Institut Claudius Regaud
Toulouse, , France
CHU TOURS (Hôpital Bretonneau)
Tours, , France
Centre de Radiothérapie Marie Curie
Valence, , France
Institut de Cancérologie de lorraine (ICL)
Vandœuvre-lès-Nancy, , France
Institut Gustave Roussy
Villejuif, , France
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefebvre JL, Greiner RH, Giralt J, Maingon P, Rolland F, Bolla M, Cognetti F, Bourhis J, Kirkpatrick A, van Glabbeke M; European Organization for Research and Treatment of Cancer Trial 22931. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004 May 6;350(19):1945-52. doi: 10.1056/NEJMoa032641.
Seiwert, TC, clement, P. M, Del Campo, J, de Mont-Serrat, H., Thurm, H. C., Blackman, A. S., and Cohen, E. E. BIBW 2992 versus cetuximab in patients with metastatic or recurrent head and neck cancer (SCCHN) after failure of platinum-containing therapy with a cross-over period for progressing patients: Preliminary results of a randomized, open-label phase II study. Journal of Clinical Oncology 28(15 suppl). 2010.
Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Machtay M, Ensley JF, Chao KS, Schultz CJ, Lee N, Fu KK; Radiation Therapy Oncology Group 9501/Intergroup. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004 May 6;350(19):1937-44. doi: 10.1056/NEJMoa032646.
Carpenter G, Cohen S. Epidermal growth factor. J Biol Chem. 1990 May 15;265(14):7709-12. No abstract available.
Mendelsohn J. Epidermal growth factor receptor inhibition by a monoclonal antibody as anticancer therapy. Clin Cancer Res. 1997 Dec;3(12 Pt 2):2703-7.
Salomon DS, Brandt R, Ciardiello F, Normanno N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol. 1995 Jul;19(3):183-232. doi: 10.1016/1040-8428(94)00144-i. No abstract available.
Grandis JR, Tweardy DJ. TGF-alpha and EGFR in head and neck cancer. J Cell Biochem Suppl. 1993;17F:188-91. doi: 10.1002/jcb.240531027.
Baselga J. New therapeutic agents targeting the epidermal growth factor receptor. J Clin Oncol. 2000 Nov 1;18(21 Suppl):54S-9S. No abstract available.
Fan Z, Mendelsohn J. Therapeutic application of anti-growth factor receptor antibodies. Curr Opin Oncol. 1998 Jan;10(1):67-73. doi: 10.1097/00001622-199801000-00011.
Milas L, Mason K, Hunter N, Petersen S, Yamakawa M, Ang K, Mendelsohn J, Fan Z. In vivo enhancement of tumor radioresponse by C225 antiepidermal growth factor receptor antibody. Clin Cancer Res. 2000 Feb;6(2):701-8.
Kaplan EL and Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457-81. 2006.
Gregoire V, Eisbruch A, Hamoir M, Levendag P. Proposal for the delineation of the nodal CTV in the node-positive and the post-operative neck. Radiother Oncol. 2006 Apr;79(1):15-20. doi: 10.1016/j.radonc.2006.03.009. Epub 2006 Apr 17.
Lapeyre M, Henrot P, Alfonsi M, Bardet E, Bensadoun RJ, Dolivet G, Favrel V, Gallocher O, Giraud P, Graff P, Guerif S, Lagarde P, Lartigau E, Marchesi V, Pommier P, Rives M, Tortochaux J, Toussaint B, Verrelle P, Bourhis J, Calais G; Groupe Oncologie Radiotherapie Tete et Cou. [Propositions for the selection and the delineation of peritumoral microscopic disease volumes in oral cavity and oropharyngeal cancers (lymph nodes excluded)]. Cancer Radiother. 2005 Jun;9(4):261-70. doi: 10.1016/j.canrad.2005.03.005. Epub 2005 Apr 25. French.
Gregoire V, Levendag P, Ang KK, Bernier J, Braaksma M, Budach V, Chao C, Coche E, Cooper JS, Cosnard G, Eisbruch A, El-Sayed S, Emami B, Grau C, Hamoir M, Lee N, Maingon P, Muller K, Reychler H. CT-based delineation of lymph node levels and related CTVs in the node-negative neck: DAHANCA, EORTC, GORTEC, NCIC,RTOG consensus guidelines. Radiother Oncol. 2003 Dec;69(3):227-36. doi: 10.1016/j.radonc.2003.09.011.
Prescribing, Recording, and Reporting Intensity-Modulated Photon-Beam Therapy (IMRT)(ICRU Report 83) ICRU Report 83, Journal of the ICRU Vol. 10 No. 1. 2011.
Chao KS, Majhail N, Huang CJ, Simpson JR, Perez CA, Haughey B, Spector G. Intensity-modulated radiation therapy reduces late salivary toxicity without compromising tumor control in patients with oropharyngeal carcinoma: a comparison with conventional techniques. Radiother Oncol. 2001 Dec;61(3):275-80. doi: 10.1016/s0167-8140(01)00449-2.
Racadot S, Thennevet I, Ouldbey Y, Kaminsky MC, Bosset M, Martin L, Tao Y, Sire C, de Raucourt D, Alfonsi M, Malaurie E, Tourani JM, Fournel P, Vauleon E, Modesto A, Rolland F, Metzger S, Pommier P, Chabaud S, Dussart S; GORTEC group. Afatinib maintenance therapy following post-operative radiochemotherapy in head and neck squamous cell carcinoma: Results from the phase III randomised double-blind placebo-controlled study BIB2992ORL (GORTEC 2010-02). Eur J Cancer. 2023 Jan;178:114-127. doi: 10.1016/j.ejca.2022.10.023. Epub 2022 Nov 9.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2010-023265-22
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
BIBW2992 ORL
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.