A Study Of Lapatinib Versus Placebo Followed By Chemoradiation In Patients With Locally Advanced Head And Neck Cancer

NCT00371566 | Completed Phase 2 Results

• 1 other identifier: EGF104334
• Study Type: interventional
• Target: 107
• Locations: 5 countries
• Sites: 9

Brief Summary

This is a study comparing the activity of lapatinib versus placebo followed by chemoradiation. This study is designed to explore the effects of lapatinib monotherapy on apoptosis/necrosis, in pre-treatment and post-treatment tumour tissue samples in subjects with locally advanced squamous cell carcinoma of head and neck.

Conditions

Squamous Cell Carcinoma of Head and Neck

Keywords

squamous cell carcinoma of head and neck; lapatinib; ErbB1/ErbB2 inhibitor; apoptosis

Outcome Measures

Primary Outcomes (1)

• Change From Baseline of the Apoptotic Index During Treatment Phase

  Apoptotic Index-TUNEL Assay is a method which counts a total of at least 1000 neoplastic nuclei(Cells with morphological changes defining cell death) subdivided in 10 fields chosen randomly at 400x magnification. A 'responder' was defined as having 20% cell death.

  Baseline and Week 2

Secondary Outcomes (32)

• Change From Baseline of Cell Proliferation Rate of the Ki-67 Proliferative Index in Tumour Biopsy Samples During Treatment Phase

  Baseline and Week 2

• Overall Radiological Response After Treatment Phase in mITT Population

  Baseline and End of Treatment (Week 2 - 6)

• Overall Radiological Response After Follow-up Phase in mITT Population

  Baseline and End of Follow-up (Week 19 - 25)

• Overall Radiological Response After Treatment Phase in ITT Population

  Baseline and End of Treatment (Week 2 - 6)

• Overall Radiological Response After Follow-up Phase in ITT Population

  Baseline and End of Follow-up (week 19 - 25)

Study Arms (2)

Lapatinib

EXPERIMENTAL

Drug: Lapatinib oral tablets

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Lapatinib oral tablets DRUG

Also known as: platinum - based chemotherapy, radiotherapy

Lapatinib

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to sign a written informed consent.
• Histologically or cytologically confirmed diagnosis of SCCHN.
• Stage III, IVA and IVB disease will be eligible, who are to receive chemoradiation therapy as primary treatment (total dose ≥ 65 Gy). Subjects with distant metastases (stage IVC) will be excluded.
• Willing and able to have a tumour biopsy taken at screening and a second tumour biopsy taken during lapatinib/placebo administration.
• 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 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.
• Eastern Cooperative Oncology Group (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 method of Cockcroft and Gault \[Cockcroft, 1976\] 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 three 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) scans.
• Life expectancy of at least 6 months as judged by the investigator.

You may not qualify if:

• Subjects with paranasal sinuses, nasopharyngeal and nasal cavity tumours;
• Subjects who have received prior systemic chemotherapy given with curative intent;
• Subjects who received prior radiotherapy;
• Prior or concurrent treatment with tyrosine kinase inhibitors;
• Use of any investigational agent within 30 days or 5 half-lives, whichever is longer, preceding the first dose of lapatinib;
• Concurrent use of CYP3A4 inducers or inhibitors;
• 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 of head and neck that was successfully treated with surgery, photodynamics or laser, will be permitted;
• Distant metastases, ie Stage IVC;
• Females or males of child-bearing potential who are sexually active, if they do not agree to practice an effective method of contraception. (For example oral contraceptives, IUD or diaphragm plus spermicide);
• Pregnant or lactating females (female patients of childbearing 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 diuretics or antiemetics (e.g. 5-HT3 antagonists) to be administered with platinum-based chemotherapy;
• The investigator considers the patient unfit for the study as a result of the medical interview, physical examinations, or screening investigations;
• Subjects taking any prohibited medication (See Section 8.2)

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (9)

GSK Investigational Site

Caen, 14076, France

Location

GSK Investigational Site

Montpellier, 34298, France

Location

GSK Investigational Site

Villejuif, 94805, France

Location

GSK Investigational Site

Athens, 142 33, Greece

Location

GSK Investigational Site

Bangalore, 560029, India

Location

GSK Investigational Site

Thiruvananthapuram, 695 011, India

Location

GSK Investigational Site

Lima, Lima Province, Lima 34, Peru

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Lapatinib; Platinum Compounds; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Inorganic Chemicals; Therapeutics

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials, MD, PhD

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: August 31, 2006
• First Posted: September 4, 2006
• Study Start: March 1, 2006
• Primary Completion: December 1, 2007
• Study Completion: December 1, 2007
• Last Updated: April 6, 2010
• Results First Posted: January 29, 2010

Record last verified: 2010-04

Locations

ES (2); GR (1); FR (3); IN (2); PE (1)