Overview

This trial is active, not recruiting.

Condition neoplasms, head and neck
Treatments lapatinib oral tablets, radiotherapy, cisplatin chemotherapy
Phase phase 2
Sponsor GlaxoSmithKline
Start date November 2006
End date June 2009
Trial size 67 participants
Trial identifier NCT00387127, EGF105884

Summary

This is a phase II study comparing the effects of lapatinib versus placebo when administered concurrently with cisplatin and radiotherapy followed by 1 year monotherapy with lapatinib or placebo. The study is designed to evaluate and compare the two treatment groups with respect to complete response rate at 6 months following chemoradiation completion.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
1500mg lapatinib orally daily
lapatinib oral tablets
Lapatinib is administered orally once daily.
radiotherapy
Radiotherapy is given either as conventional fractionation using Two-dimensional (2D) or conformal techniques, or as Intensity Modulated Radiation Therapy (IMRT). Radiation therapy will be standardised throughout the study. Radiation therapy is given only once daily, with a dose/fraction not exceeding 2.5Gy, to a total dose of 65 Gy (IMRT) or 70 Gy (2D or 3D RT) to the gross site of disease .
cisplatin chemotherapy radiotherapy
Cisplatin is administered intravenously at a dose of 100mg/m2 on days 1, 22 and 43 of radiotherapy (approximately Study Days 8, 29 and 50).
(Placebo Comparator)
orally daily
lapatinib oral tablets
Lapatinib is administered orally once daily.
radiotherapy
Radiotherapy is given either as conventional fractionation using Two-dimensional (2D) or conformal techniques, or as Intensity Modulated Radiation Therapy (IMRT). Radiation therapy will be standardised throughout the study. Radiation therapy is given only once daily, with a dose/fraction not exceeding 2.5Gy, to a total dose of 65 Gy (IMRT) or 70 Gy (2D or 3D RT) to the gross site of disease .
cisplatin chemotherapy radiotherapy
Cisplatin is administered intravenously at a dose of 100mg/m2 on days 1, 22 and 43 of radiotherapy (approximately Study Days 8, 29 and 50).

Primary Outcomes

Measure
Complete response rate (as assessed by RECIST criteria) at six months after completion of chemoradiation treatment
time frame: Six months post chemoradiation treatment

Secondary Outcomes

Measure
Progression-free survival at one year, overall survival, disease-specific survival, loco-regional control, distant relapse, volumetric tumour response measurements, adverse events, intratumoral biomarker expression
time frame: six-months to one year
Disease-specific survival; loco-regional control; Distant relapse; Volumetric tumour response measurements; Adverse events; Changes in serum ErbB1 ECD levels related to disease control rate
time frame: two to four years
Other intratumoural biomarker expression and relationship to disease control rate; Proteomic profile in peripheral blood; Analysis of DNA, RNA and determining HPV infection from tumour samples
time frame: end of study

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion criteria: - Willing and able to sign a written informed consent; - Histologically confirmed diagnosis of SCCHN of one or more of the following sites: oral cavity, oropharynx, hypopharynx and larynx; Multiple primary tumours will: Have to be histologically proven; Have to be anatomically distant and surrounded by normal tissue; Exclude distant metastasis. - Prior to enrolment subjects must have ErbB1 over-expression determined by immunohistochemistry (IHC) 3+ as assessed by a central laboratory; - Subjects with stage III and IVA/IVB disease, who are to receive cisplatin chemotherapy and radiation therapy as primary treatment (total dose 65 - 70 Gy); Subjects with any Tis, T1 or T2 disease regardless of N stage, are excluded. Subjects with distant metastases, ie Stage IVC, are excluded. - Willing and able to have a tumour biopsy taken at screening; For patients who have had prior tumour biopsy, an adequate archived specimen must be available. - Male or female ≥18 years of age; Criteria for female subjects or female partners of male subjects: Non-child-bearing potential (i.e., women with functioning ovaries who have a GM2005/00448/00 CONFIDENTIAL EGF105884 22 current documented tubal ligation or hysterectomy, or women who are postmenopausal); Child-bearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility.) This category includes women with oligomenorrhoea (severe), women who are perimenopausal, and young women who have begun to menstruate. These subjects must have a negative serum pregnancy test at screening and agree to one of the following: Complete abstinence from intercourse from 2 weeks prior to administration of the first dose of study medication until 28 days after the final dose of study medication; 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; implants of levonorgestrel; injectable progestogen; any intrauterine device (IUD) with a documented failure rate of less than 1% per year; oral contraceptives (either combined or progestogen only); or barrier methods, including diaphragm or condom with a spermicide. - ECOG performance status 0, 1 or 2; - Subjects must have adequate haematological, renal and hepatic function; Calculated creatinine clearance ≥50 ml/min as determined by the modified method of Cockcroft and Gault or by the EDTA method. Absolute neutrophil count ≥1,500/μl, platelets ≥100,000/μl. Haemoglobin ≥9gm/dL (5mmol/L). Aspartate (AST) and alanine transaminase (ALT) less than 4 times the upper limit of the normal range (ULN). Total bilirubin ≤2.0 mg/dL. - Left ventricular ejection fraction (LVEF) within the institutional normal ranges as measured by echocardiogram (ECHO) or Multigated Acquisition (MUGA) scan; - Able to swallow tablets whole or swallow a suspension of tablets dissolved in water at study inclusion; The use and timing 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 judgment of the investigator. Exclusion criteria: - Nasopharyngeal, paranasal sinuses or nasal cavity tumours; - Any prior or current treatment for invasive head and neck cancer of any kind. This will include but is not limited to: prior tyrosine kinase inhibitors, prior neoadjuvant therapy, prior surgical resection, or use of any investigational agent; - Concurrent use of CYP3A4 inducers or inhibitors. A standard 3-day course of dexamethasone for the prevention of cisplatin-induced nausea and vomiting is permitted; - Subjects with known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure; - 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, including in the head and neck region that was successfully treated with surgery, photodynamics or laser, will be permitted; - Peripheral neuropathy ≥ grade 2; - Pregnant or lactating females (female subjects of child-bearing potential will undertake pregnancy testing at screening and during study completion/withdrawal visits); - Malabsorption syndrome, disease significantly affecting GI function, that could affect absorption of lapatinib; - History of allergic reactions to appropriate antiemetics (e.g. 5-HT3 antagonists) to be administered with platinum chemotherapy; - The investigator considers the subject unfit for the study as a result of the medical interview, physical examinations, or screening investigations;

Additional Information

Official title A Randomized, Double-blind, Placebo Controlled, Multicentre, Phase II Study of Oral Lapatinib in Combination With Concurrent Radiotherapy and Cisplatin Versus Radiotherapy and Cisplatin Alone, in Subjects With Stage III, IVA, B Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Trial information was received from ClinicalTrials.gov and was last updated in February 2014.
Information provided to ClinicalTrials.gov by GlaxoSmithKline.