Afatinib (BIBW 2991) versus placebo after chemo-radiotherapy to patients with head and neck cancer

Phase 1

• Conditions: oco-regionally advanced head and head squamous cell carcinoma with no evidence of disease after chemo-radiotherapy; MedDRA version: 14.1Level: LLTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-000392-14-IT
• Lead Sponsor: BOEHRINGER ING.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-12-19
• Last Update Posted: 29 August 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 847

Inclusion Criteria

1. Histologically or cytologically confirmed loco-regionally advanced squamous cell carcinoma a) stage III, IVa, or IVb, of the oral cavity, oropharynx, or hypopharynx; or b) larynx stage IVa or IVb 2. Unresected tumour prior to chemo-radiotherapy due to: a)Technical unresectability (tumour fixation/invasion to either base of the skull, cervical vertebrae, nasopharynx, or fixed lymph nodes); and/or b)Low surgical curability (T3-T4, N2-N3 excluding T1N2); and/or c) Organ preservation 3.Concomitant platinum-based chemo-radiotherapy completed no longer than 16 weeks prior to randomisation: a)Head and neck radiotherapy with curative intent to a dose of minimum 66 Gy in 33 fractions (or its radiobiological equivalent) with adequate nodal coverage. Radiation period 6 to 8 weeks, and cumulative break in radiotherapy for no more than 10 days; and b) At least two cycles of either cisplatin (minimum cumulative dose of 200 mg/m2) or carboplatin (minimum cumulative area under the concentrationtime curve (AUC) 9); and c) At randomisation, chemo-radiotherapy induced side effects CTCAE grade <= 2 (exception: patients with feeding tube are eligible if the patient has recovered from the AE mandating the feeding tube) 4. Within 16 weeks after concomitant platinum-based CRT, no evidence of disease (NED), defined as no residual tumour, i.e. no measurable or palpable tumour on clinical and radiographic (e.g. CT scan or MRI) examination as judged by the investigator. In case of palpable mass, NED must be confirmed by biopsy 5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at the time of randomisation 6. Male and female patients age > 18 years 7. Written informed consent that is in compliance with ICH GCP and local law
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 763
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 84

Exclusion Criteria

1. Simultaneous HNSCC primaries 2. Patients with smoking history of <= 10 pack years and with primary tumour site base of tongue 3. Patients with smoking history of <= 10 pack years and with primary tumour site tonsil 4. Primary cancer of nasopharynx, sinuses, and/or salivary glands 5. Surgery of the primary tumour or involved lymph nodes (isolated biopsies are not counted as surgical procedures) prior to chemo-radiotherapy 6. Any other malignancy (except for appropriately treated superficial basal cell skin cancer and surgically cured cervical cancer in situ) unless free of disease for at least five years 7. Treatment with any investigational drug or anti-cancer therapy less than four weeks prior to randomisation 8. Prior treatment with any EGFR-targeted small molecules, EGFR-targeted antibodies, and/or any investigational agents for treatment of HNSCC 9. Requirement for treatment with any of the prohibited concomitant medications listed in Section 4.2.2.1 10. Known pre-existing interstitial lung disease (ILD) 11. Clinically relevant cardiovascular abnormalities, as judged by the investigator, such as, but not limited to, uncontrolled hypertension, congestive heart failure NYHA classification > III, unstable angina, myocardial infarction within six months prior to randomisation, or poorly controlled arrhythmia 12. Cardiac left ventricular dysfunction with resting ejection fraction of less than institutional lower limit of normal (if no lower limit of normal is defined in the institution, the lower limit is 50%) 13. Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom e.g. Crohn's disease, malabsorption or CTCAE grade >1 diarrhoea of any aetiology at randomisation 14. Known HIV, active hepatitis B and/or active hepatitis C, at the discretion of the investigator 15. Other significant disease that in the investigator's opinion would exclude the subject from the trial 16. Screening laboratory values based on central laboratory analysis: a) Absolute neutrophil count (ANC) <1.5x10**9/l b) Platelet count <75x10**9/l c) Total bilirubin >1.5 times the upper limit of normal (ULN) d) Aspartate amino transferase (AST) or alanine amino transferase (ALT) > 3 times the ULN e) Calculated creatinine clearance < 50 ml/min (using the Cockcroft-Gault formula, see Appendix 1) 17. Women of child-bearing potential and men who are able to father a child, unwilling to be abstinent or to use adequate contraception during the trial and for at least two months after end of treatment. Adequate methods of contraception and definition of child-bearing potential are described in Section 5.2.2.2.1 18.Pregnancy or breast feeding 19.Known or suspected hypersensitivity to the study medication or the excipients 20.Patients unable to comply with the protocol in the opinion of the investigator

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified