Afatinib (BIBW 2992) versus methotrexate in recurrent and/or metastatic (R/M) head and neck cancer patients who have progressed after chemotherapy
- Conditions
- Recurrent and/or metastatic head and neck squamous cell carcinoma in patients who have progessed after platinum based therapyMedDRA 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
- EUCTR2011-000391-34-IT
- Lead Sponsor
- BOEHRINGER ING.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 595
1.Histologically or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, which has recurred/metastasised and is not amenable for salvage surgery or radiotherapy. 2.Documented progressive disease based on investigator assessment according to RECIST, following receipt of cisplatin and/or carboplatin (minimum doses described below*) administered for recurrent and/or metastatic disease independent of whether patient progressed during or after platinum based therapy: -Cisplatin, minimum dose: at least two cycles of cisplatin, >=60 mg/m2/cycle or a total cumulative dose of >=120 mg/m2 during eight weeks; -Carboplatin, minimum dose: at least two cycles of carboplatin area under the concentration-time curve (AUC) >=4/cycle or a total cumulative dose of AUC >=8 during eight weeks.*if cisplatin is switched to carboplatin (or vice versa, e.g due to intolerance), the following conversion should be used for calculation of minimum cumulative platinum dose: carboplatin 1 AUC = cisplatin 15 mg/m**2. 3. Measurable disease according to RECIST (version 1.1). 4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at the time of randomisation. 5. Male and female patients age >=18 years. 6. 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 534
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 61
1. Progressive disease within three months after completion of curatively intended treatment for locoregionally advanced or for metastatic HNSCC. 2. Primary tumour site nasopharynx (of any histology), sinuses, and/or salivary glands. 3. Any other than one previous platinum based systemic regimen given for recurrent and/or metastatic disease. Re-challenge with the first line regimen after a temporary break is considered a second line regimen only in case of progression within the break. 4. Prior treatment with EGFR-targeted small molecules. 5. Treatment with any investigational drug or anti-cancer therapy less than four weeks prior to randomisation (except palliative radiotherapy to bones to alleviate pain). 6. Unresolved chronic toxicity, other than hearing loss, tinnitus or dry mouth, CTCAE grade >2 from previous anti-cancer therapy or unresolved skin toxicities CTCAE grade >1 and/or diarrhoea CTCAE grade >1 caused by prior treatment with EGFR targeted antibodies. 7. Previous tumour bleeding CTCAE grade >=3. 8. Requirement for treatment with any of the prohibited concomitant medications listed in Section 4.2.2. 9. Major surgical or planned procedure less than four weeks prior to randomisation (isolated biopsies are not counted as major surgical procedures). 10. 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. 11. Known brain metastasis or signs thereof. 12. Known pre-existing interstitial lung disease (ILD). 13. 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. 14. Cardiac left ventricular dysfunction with resting ejection fraction of less than institutional lower limit of normal (LLN) (if no LLN is defined in the institution, the lower limit is 50%). 15. Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom e.g. Crohn`s disease, malabsorption or CTCAE grade >1 diarrhoea of anyaetiology at randomisation. 16. Known HIV, active hepatitis B, active hepatitis C and/or other known severe infections, including but not limited to tuberculosis, as judged by the investigator 17. Other significant disease that in the investigator`s opinion would exclude the subjectfrom the trial. 18. Screening laboratory values based on central laboratory analysis: a) Absolute neutrophil count (ANC) <1.5x109/l b) Platelet count <75x109/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 (if related to liver metastases >5 times the ULN) e) Calculated creatinine clearance <50 ml/min (as evidenced by using the Cockcroft-Gault formula, see Appendix 2). 19. 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 six months after end of treatment. Adequate methods of contraception and definition of child-bearing potential are described in Section 5.2.2.2.1. 20. Pregnancy or breast feeding. 21. Known or suspected hypersensitivity to any of the study medications or their excipients. 22. Patients unable to comply with t
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To investigate the efficacy of afatinib versus methotrexate therapy in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who have progressed after platinumbased therapy given for R/M HNSCC;Secondary Objective: To investigate the safety of afatinib versus methotrexate therapy in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who have progressed after platinumbased therapy given for R/M HNSCC;Primary end point(s): Progression Free Survival (PFS);Timepoint(s) of evaluation of this end point: After 364 disease progression events, estimated to be approximately 20 months after start of recruitment.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Key secondary endpoint is Overall Survival (OS). Other secondary enpoints are Objective Response and Health related quality of life (HRQOL).;Timepoint(s) of evaluation of this end point: After 343 death events, estimated to be approximately 26 months after start of recruitment. For the key secondary endpoint OS a futility analysis will be made after approximately 40% of the death events, estimated to be after 14 months after start of recuitment.