Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00005528

Trial Description

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Title

A Randomised, Double-Blind, Placebo-Controlled, Multi-centre, Phase III Study of Post-Operative Adjuvant Lapatinib or Placebo and Concurrent Chemoradiotherapy Followed by Maintenance Lapatinib or Placebo Monotherapy in High-Risk Subjects With Resected Squamous Cell Carcinoma of the Head and Neck (SCCHN)

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

This is a randomised, double-blind, placebo-controlled, multicentre, global Phase III trial
comparing the efficacy of adjuvant oral lapatinib versus placebo in high-risk subjects with
head and neck cancer following surgery. Lapatinib or placebo will be administered
post-operatively in combination with chemoradiotherapy followed by maintenance with
lapatinib or placebo for 1 year. The primary goal is to determine if lapatinib is effective
at reducing the recurrence of the disease in these high-risk patients.

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Brief Summary in Scientific Language

A Randomised, Double-Blind, Placebo-Controlled, Multi-centre, Phase III Study of
Post-Operative Adjuvant Lapatinib or Placebo and Concurrent Chemoradiotherapy Followed by
Maintenance Lapatinib or Placebo Monotherapy in High-Risk Subjects with Resected Squamous
Cell Carcinoma of the Head and Neck (SCCHN)

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Organizational Data

  •   DRKS00005528
  •   2014/02/20
  •   2007/01/17
  •   no
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Secondary IDs

  •   NCT00424255  (ClinicalTrials.gov)
  •   EGF102988  (GlaxoSmithKline)
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Health Condition or Problem studied

  •   Neoplasms, Head and Neck
  •   C01 -  Malignant neoplasm of base of tongue
  •   C02 -  Malignant neoplasm of other and unspecified parts of tongue
  •   C03 -  Malignant neoplasm of gum
  •   C04 -  Malignant neoplasm of floor of mouth
  •   C05 -  Malignant neoplasm of palate
  •   C06 -  Malignant neoplasm of other and unspecified parts of mouth
  •   C10 -  Malignant neoplasm of oropharynx
  •   C13 -  Malignant neoplasm of hypopharynx
  •   C32 -  Malignant neoplasm of larynx
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Interventions/Observational Groups

  •   Drug: Lapatinib
  •   Radiation: Chemoradiation
  •   Other: Placebo
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, investigator/therapist
  •   Placebo
  •   Treatment
  •   Parallel
  •   III
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Primary Outcome

- Disease-free survival measured by the time from the start of the study that a subject is free from disease (cancer recurrence or death from any cause); time frame: 1 Year

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Secondary Outcome

- Overall survival from start to end of studyDisease-specific survival from start to end of studyTime to recurrence of cancer from start to end of studySafety from start to end of studyQuality of life from start to end of study; time frame: 1 Year
- Disease-specific survival Time to locoregional recurrence Incidence of second primary tumour Time to distant relapse Qualitative and quantitative toxicities, including late morbidities; time frame: 1 Year
- Change in quality of life (QoL) status relative to baseline using the FACT H&N and EQ-5D instruments. Clinical outcome with relevant biomarkers and genetic changes in serum, plasma, and tumour samples.; time frame: 1 Year

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Countries of Recruitment

  •   Argentina
  •   Austria
  •   Canada
  •   China
  •   Croatia
  •   Czech Republic
  •   Estonia
  •   France
  •   Germany
  •   Greece
  •   Hong Kong
  •   Hungary
  •   India
  •   Italy
  •   Philippines
  •   Russian Federation
  •   Slovakia
  •   Spain
  •   Thailand
  •   United Kingdom
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Locations of Recruitment

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Recruitment

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  •   2006/12/31
  •   680
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   70   Years
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Additional Inclusion Criteria

- Willing and able to sign a written informed consent.

- Histologically confirmed diagnosis of SCCHN of one of the following sites: oral
cavity, oropharynx, hypopharynx and larynx.

- Pathological Stage II, III or IVa (according to AJCC cancer staging criteria [Green,
2002]) with no evidence of gross residual disease, and at least one of the following
high risk factors by pathology:

- Extracapsular extension of nodal disease

- Positive resection margin (5 mm or less)

- Primary surgery with a curative intent completed within 4-6 weeks (and no later than
7 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:

- Clear : (R0) > 5mm.

- Close: (R1) 1 - 5mm.

- Involved: (R2) <1mm

- Complete recovery from the surgical procedure allowing for appropriate radiotherapy.
Radiation therapy is required to start as soon as adequate healing has occurred.
This is normally around 4-6 weeks but no later than 9 weeks after surgery.

- Adequate tumour specimen from archived or resected tissue must be available for IHC
evaluation of ErbB1 expression levels in a central laboratory and subsequent
biomarker analysis.

- Male or female, between 18 and 70 years of age [Bourhis, 2006].

Criteria for female subjects or female partners of male subjects:

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

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:

Complete abstinence from intercourse from the time of the screening pregnancy test until
28 days after the final dose of test article; or

Consistent and correct use of one of the following acceptable methods of birth control:

Male partner who is sterile prior to the female subject's entry into the study and is the
sole sexual partner for that female subject; or Oral contraceptives (either combined or
progestogen only), or Injectable progestogen-only contraceptives or Implants of
levonorgestrel, or Any intrauterine device with a documented failure rate of less than 1%
per year; or Barrier methods (e.g. condoms, diaphragms, caps) only if used in combination
with one of the above acceptable methods.

- ECOG performance status 0, 1 or 2

- Adequate haematology, renal and hepatic function Absolute neutrophil count ≥
1,500/μL, platelets ≥ 100,000/μL Haemoglobin ≥ 9 gm/dL (5mmol/L) Calculated
creatinine clearance ≥60 ml/min as determined by the modified method of Cockcroft and
Gault.

Aspartate (AST) and alanine transaminase (ALT) less than 3 times the upper limit of the
normal range (ULN).

Total bilirubin ≤ 2.0 mg/dL

- Left ventricular ejection fraction (LVEF) above the lower limits of 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).

- Able to swallow and retain tablets whole or swallow a suspension of tablets dissolved
in water at study inclusion.

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).

- Life expectancy of at least 6 months in the best judgement of the investigator

- Current active hepatic or biliary disease (with exception of patients with Gilbert's
syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator
assessment).

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Exclusion Criteria

- Nasopharyngeal, paranasal sinuses or nasal cavity tumours

- Head and neck cancer with histology other than squamous cell carcinoma.

- Evidence of distant metastases or gross post-operative residual disease.

- Evidence of second primary tumour.

- Any prior or current anticancer treatment of any kind - except the primary surgical
resection. This will include but is not limited to: prior tyrosine kinase inhibitors,
prior neoadjuvant therapy, prior radiotherapy or use of any investigational agent.

- Concurrent treatment with an investigational agent or participation in another
clinical trial.

- Concurrent use of CYP3A4 inducers or inhibitors while on lapatinib/placebo. A
standard 3 to 5 day course of dexamethasone for the prevention of cisplatin induced
nausea and vomiting is permitted. In addition glucocorticoid daily doses (oral) 1.5mg
dexamethasone (or equivalent) are allowed.

- Subjects with known history of uncontrolled or symptomatic angina, arrhythmias, or
congestive heart failure;

- 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. History of non-invasive lesion or in-situ carcinoma, that was
successfully treated with surgery, photodynamics or laser, will be permitted;

- Peripheral neuropathy ≥ grade 2

- Mal-absorption syndrome, disease significantly affecting GI function, or major
resection of the stomach or bowel, that could affect absorption of lapatinib.

- History of allergic reactions to relevant diuretics or anti-emetics (e.g 5-HT3
antagonists) to be administered with cisplatin chemotherapy

- History of allergic reactions attributed to compounds of similar chemical composition
(quinazolines) to lapatinib

- The investigator considers the subject unfit for the study as a result of the medical
interview, physical examinations, or screening investigations

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Addresses

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    • GlaxoSmithKline
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    • GlaxoSmithKline
    • GSK Clinical Trials 
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    • GlaxoSmithKline
    • GSK Clinical Trials 
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Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting complete, follow-up continuing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   1
  •   2013/12/01
* This entry means the parameter is not applicable or has not been set.