E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Squamous cell carcinoma of the head and neck (SCCHN) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060121 |
E.1.2 | Term | Squamous cell carcinoma of head and neck |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate and compare DFS from randomisation to the end of the study in high-risk subjects with resected stage III or IVa SCCHN treated with adjuvant placebo or lapatinib and chemoradiotherapy followed by maintenance placebo or lapatinib for 1 year. |
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E.2.2 | Secondary objectives of the trial |
Overall survival ユ Disease-specific survival ユ Time to locoregional recurrence ユ Time to development of second primary tumour ユ Time to distant relapse ユ Qualitative and quantitative toxicities, including late morbidities ユ Change in quality of life (QoL) status relative to baseline. ユ Clinical outcome with relevant biomarkers and genetic changes in serum, plasma, and intra-tumoural samples. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1)Willing and able to sign a written informed consent. 2)Histologically confirmed diagnosis of SCCHN of one of the following sites: oral cavity, oropharynx, hypopharynx and larynx. 3)Pathological Stage II, III or IVa (according to AJCC cancer staging criteria [Green, 2002]) with no evidence of gross residual diease, and at least one of the following high risk factors by pathology: ユ Extracapsular extension of nodal disease ユ Close (<5mm) or involved resection margin (<1mm) 4)Primary surgery with a curative intent completed within 4-6 weeks (and no later than 8 weeks) prior to randomization. The extent of surgical resection will follow accepted criteria for adequate excision [Helliwell, 2005]. Surgical margins are divided into 'mucosal' and 'deep', and for each category the resection margin (R) is classified as: ユ Clear : R > 5mm ユ Close: R 1- 5mm ユ Involved: R <1mm 5)Complete recovery from the surgical procedure. Radiation therapy is required to start as soon as adequate healing has occurred. This is normally around 4-6 weeks but no later than 8 weeks after surgery. 6)Adequate tumour specimen must be available. 7)Subjects must have ErbB1 over-expression in tumour tissue determined by immunohistochemistry (IHC) 3+ as assessed by a central laboratory; 8)Male or female, between 18 and 70 years of age [Bourhis, 2006]. Criteria for female subjects or female partners of male subjects: a. Non-child-bearing potential (i.e., a woman with functioning ovaries who has a current documented tubal ligation or hysterectomy or a woman who is menopausal); or b. Child-bearing potential (i.e. a woman with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility. This category includes women with oligomenorrhoea (even severe), women who are perimenopausal and young women who have begun to menstruate), who have a negative serum pregnancy test at screening, and agree to one of the following: i. Complete abstinence from intercourse from the time of the screening pregnancy test until 28 days after the final dose of test article; or ii. Consistent and correct use of one of the following acceptable methods of birth control: ユ Male partner who is sterile prior to the female patientメs entry into the study and is the sole sexual partner for that female patient; or ユ Oral contraceptives (either combined or progestogen only), or ユ Injectable progestogen-only contraceptives or ユ Implants of levonorgestrel, or ユ Any intrauterine device (IUD) with a documented failure rate of less than 1% per year; or ユ Barrier methods (e.g. condoms, diaphragms, caps) only if used in combination with one of the above acceptable methods. 9. ECOG performance status 0, 1 or 2 10. Adequate haematology, renal and hepatic function ユ Absolute neutrophil count >= 1,500/ᄉL, platelets >= 100,000/ᄉL ユ Haemoglobin >= 9 gm/dL (5mmol/L) ユ Calculated creatinine clearance >=60 ml/min as determined by the modified method of Cockcroft and Gault. ユ Aspartate (AST) and alanine transaminase (ALT) less than 3 times the upper limit of the normal range (ULN). ユ Total bilirubin <= 2.0 mg/dL 11. Left ventricular ejection fraction (LVEF) within the institutional normal range as measured by ECHO (if ECHO cannot be performed or if the Investigator feels it is not conclusive to evaluate LVEF, then a MUGA scan should be performed). 12. Able to swallow and retain tablets whole or swallow a suspension of tablets dissolved in water at study inclusion. ユ The use of feeding tube is optional. If necessary, the suspension may be administered via percutaneous endoscopic gastrostomy (PEG), percutaneous jejunostomy tube (J- Tube), or a nasogastric tube (NG or Dobhoff type tube). 13. Life expectancy of at least 6 months in the best judgement of the investigator |
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E.4 | Principal exclusion criteria |
1. Nasopharyngeal, paranasal sinuses or nasal cavity tumours 2)Head and neck cancer with histology other than squamous cell. 3)Evidence of distant metastases or gross post-operative residual disease. 4)Any prior or current anticancer treatment of any kind ヨ except the primary surgical resection. This will include but not exclusive to: prior tyrosine kinase inhibitors, prior neoadjuvant therapy, prior radiotherapy or use of any investigational agent. 5)Concurrent use of CYP3A4 inducers or inhibitors while on investigational product. A standard 3-day course of dexamethasone for the prevention of cisplatin induced nausea and vomiting is permitted. 6)Subjects with known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure; 7)Pregnant or lactating females History of another malignancy within the last 5 years, with the exception of completely resected basal or squamous cell skin cancer, or successfully treated in-situ carcinoma. 8)History of non-invasive lesion or in-situ carcinoma, including in the head and neck region that was successfully treated with surgery, photodynamics or laser, will be permitted; 9)Peripheral neuropathy >= grade 2 10)Mal-absorption syndrome, disease significantly affecting GI function, or major resection of the stomach or bowel, that could affect absorption of lapatinib. 11)History of allergic reactions to relevant diuretics or anti-emetics (e.g. 5-HT3 antagonists) to be administered with cisplatin chemotherapy 12)History of allergic reactions attributed to compounds of similar chemical composition (quinazolines) to lapatinib 13)The investigator considers the patient unfit for the study as a result of the medical interview, physical examinations, or screening investigations |
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate and compare disease free survival (DFS) from randomisation to the end of the study in high-risk subjects with resected SCCHN treated with adjuvant placebo or lapatinib for one year |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 8 |