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Head and Neck Squamous Cell CarcinomaPhase 3BIBW2992ORLNCT01427478

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

A Phase 3 study testing AFATINIB in people with Head and Neck Squamous Cell Carcinoma, run by Centre Leon Berard at 26 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Head and Neck Squamous Cell Carcinoma
What is being tested?
AFATINIB
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
134 participants
Where
26 sitesFrance
Study dates
Sep 2011to May 2021
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
Show all 13Show fewer
  • 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.

Who cannot join

  • 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.
Show all 16Show fewer
  • 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

Trial locations and contacts

26 sites in 1 country.

26 sites in 1 country

France26 sites

  • Centre Paul Papin

    Angers, 49933

  • Institut Sainte-Catherine

    Avignon, 84000

  • CHU Bordeaux - Hôpital Saint-André

    Bordeaux, 33075

  • Polyclinique de Bordeaux Nord

    Bordeaux, 33300

  • CHRU Brest - Hôpital Morvan

    Brest, 29609

  • Centre François Baclesse

    Caen, 14076

  • CHIC Créteil

    Créteil, 94010

  • Centre Guillaume le Conquérant

    Le Havre, 76600

  • Centre Hospitalier Bretagne Sud

    Lorient, 56100

  • Centre Léon Bérard

    Lyon, 69373

  • AP-HM La Timone Adultes

    Marseille, 13386 Cedex

  • Centre Antoine Lacassagne

    Nice, 06189

  • CHU Poitiers

    Poitiers, 86021

  • Centre Eugène Marquis

    Rennes, 44229

  • Centre Henri Becquerel

    Rouen, 76038

  • Institut de Cancérologie de l'Ouest

    Saint-Herblain, 44805

  • Pôle Hospitalier Mutualiste- Centre Etienne Dolet

    Saint-Nazaire, 44600

  • Institut de Cancérologie de la Loire

    Saint-Priest-en-Jarez, 42270

  • Strasbourg Oncologie Libérale

    Strasbourg, 67000

  • Hopitaux du Léman

    Thonon-les-Bains, 74203

  • Clinique Pasteur Bâtiment l'Atrium

    Toulouse, 31076

  • Institut Claudius Regaud

    Toulouse, 71000

  • CHU TOURS (Hôpital Bretonneau)

    Tours, 37044

  • Centre de Radiothérapie Marie Curie

    Valence, 26000

  • Institut de Cancérologie de lorraine (ICL)

    Vandœuvre-lès-Nancy, 54519 cedex

  • Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

About this study

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

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.

Read the 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.

Being tested
AFATINIB, Placebo of AFATINIB
Keywords
Head and neck squamous cell carcinoma, Post operative radio-chemotherapy, Randomisation, Maintenance treatment, Afatinib
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AFATINIBDrug

    Also called BIBW 2992

    AFATINIBat the dose of 40 mg/during the 1st month and then 50 mg/d during the 11 following months

  • Placebo of AFATINIBDrug

    Also called Placebo of BIBW 2992

    placebo of Afatinib at the dose of 40 mg/during the 1st month and then 50 mg/d during the 11 following months

Study groups in NCT01427478
Study groupRoleWhat they receive
AFATINIBExperimentalRadiotherapy 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
Receives: Drug: AFATINIB
PLACEBOPlacebo comparatorRadiotherapy 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
Receives: Drug: Placebo of AFATINIB

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease Free Survival 2 years after the end of radiotherapy

    Measured: 2 years after the end of radiotherapy

Secondary outcomes (3)

  1. Safety profile

    Safety profile is characterized by type; frequency and seriousness of the toxicities showed by the patients and graded using CTCAE - V04

    Measured: 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

  2. Quality of life of patient, evaluated by questionnary

    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.

    Measured: Baseline; at the end of radiotherapy, at 1 and 2 years after the beginning of maintenance treatment

  3. Overall Survival (OS)

    OS is the time from randomization to the date of death due to any cause or date of the last news.

    Measured: Death

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Sep 2011 (estimated)
  2. Study startSep 2011
  3. Primary completionNov 2020
  4. Study completionMay 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
134 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01427478
Sponsor's protocol ID
BIBW2992 ORL
Other IDs
2010-023265-22
Acronym
BIBW2992ORL
Status last verified
May 2021
First submitted
31 Aug 2011
Last updated
1 Jun 2021
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 15128894

  • 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.

    PubMed 15128893

  • Carpenter G, Cohen S. Epidermal growth factor. J Biol Chem. 1990 May 15;265(14):7709-12. No abstract available.

    PubMed 2186024

  • 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.

    PubMed 10068277

  • 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.

    PubMed 7612182

  • 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.

    PubMed 8412192

  • 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.

    PubMed 11060328

  • 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.

    PubMed 9466487

  • 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.

    PubMed 10690556

  • 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.

    PubMed 16616387

  • 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.

    PubMed 16081023

  • 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.

    PubMed 14644481

  • 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.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing AFATINIB in people with Head and Neck Squamous Cell Carcinoma, run by Centre Leon Berard at 26 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease Free Survival 2 years after the end of radiotherapy (time frame: 2 years after the end of radiotherapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01427478, which also lists 17 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2021.

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