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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01427478
Recruitment Status : Completed
First Posted : September 1, 2011
Last Update Posted : June 1, 2021
Boehringer Ingelheim
Information provided by (Responsible Party):
Centre Leon Berard

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.

Condition or disease Intervention/treatment Phase
Head and Neck Squamous Cell Carcinoma Drug: AFATINIB Drug: Placebo of AFATINIB Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 134 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : September 2011
Actual Primary Completion Date : November 2020
Actual Study Completion Date : May 2021

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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
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

Primary Outcome Measures :
  1. Disease Free Survival 2 years after the end of radiotherapy [ Time Frame: 2 years after the end of radiotherapy ]

Secondary Outcome Measures :
  1. 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 ]
    Safety profile is characterized by type; frequency and seriousness of the toxicities showed by the patients and graded using CTCAE - V04

  2. Quality of life of patient, evaluated by questionnary [ Time Frame: Baseline; at the end of radiotherapy, at 1 and 2 years after the beginning of maintenance treatment ]
    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.

  3. Overall Survival (OS) [ Time Frame: Death ]
    OS is the time from randomization to the date of death due to any cause or date of the last news.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01427478

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Sponsors and Collaborators
Centre Leon Berard
Boehringer Ingelheim
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Principal Investigator: Séverine RACADOT, MD Centre Léon Bérard; Lyon
Principal Investigator: Pascal POMMIER, MD Centre Léon Bérard , Lyon
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.
Kaplan EL and Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457-81. 2006.
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.

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Responsible Party: Centre Leon Berard Identifier: NCT01427478    
Other Study ID Numbers: BIBW2992 ORL
2010-023265-22 ( EudraCT Number )
First Posted: September 1, 2011    Key Record Dates
Last Update Posted: June 1, 2021
Last Verified: May 2021
Keywords provided by Centre Leon Berard:
Head and neck squamous cell carcinoma
Post operative radio-chemotherapy
Maintenance treatment
Additional relevant MeSH terms:
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Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action