Clinical trial NCT00371566: A Study Of Lapatinib Versus Placebo Followed By Chemoradiation In Patients With Locally Advanced Head And Neck Cancer
Official title: A Randomized, Single Blinded, Placebo-controlled, Multi-centre, Phase II Study of Lapatinib in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Squamous Cell Carcinoma of Head and Neck
Keywords: squamous cell carcinoma of head and neck
lapatinib
ErbB1/ErbB2 inhibitor
apoptosis
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-09-04
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion criteria:

* 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.
* Able to swallow tablet whole or swallow a suspension of the tablet dissolved in water at study inclusion. If necessary, the suspension may be administered via percutaneous endoscopic gastrostomy (PEG), percutaneous jejunostomy tube (JTube), or a nasogastric tube (NG or Dobhoff type tube).
* Life expectancy of at least 6 months as judged by the investigator.

Exclusion criteria:

* 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)

Other Eligibility Criteria Considerations:

To assess any potential impact on subject eligibility with regard to safety, the investigator must refer to the following document(s) for detailed information regarding warnings,precautions, contraindications, adverse events, and other significant data pertaining to the investigational product(s) being used in this study: investigator's brochure IB and any IB supplements, and expedited investigator safety reports

Primary outcomes:
measure: Change From Baseline of the Apoptotic Index During Treatment Phase
timeFrame: Baseline and Week 2
Secondary outcomes:
measure: Change From Baseline of Cell Proliferation Rate of the Ki-67 Proliferative Index in Tumour Biopsy Samples During Treatment Phase
timeFrame: Baseline and Week 2
measure: Overall Radiological Response After Treatment Phase in mITT Population
timeFrame: Baseline and End of Treatment (Week 2 - 6)
measure: Overall Radiological Response After Follow-up Phase in mITT Population
timeFrame: Baseline and End of Follow-up (Week 19 - 25)
measure: Overall Radiological Response After Treatment Phase in ITT Population
timeFrame: Baseline and End of Treatment (Week 2 - 6)
measure: Overall Radiological Response After Follow-up Phase in ITT Population
timeFrame: Baseline and End of Follow-up (week 19 - 25)
measure: Number of Circulating Tumor Cells at Baseline in mITT Population
timeFrame: Baseline
measure: Number of Participants With Circulating Tumor Cells After Treatment Phase in mITT Population
timeFrame: End of Treatment (week 2 - 6)
measure: Number of Participants With Circulating Tumor Cells After Chemoradiotherapy Phase in mITT Population
timeFrame: End of Chemoradiotherapy (week 10 - 13)
measure: Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase
timeFrame: Baseline and Week 2
measure: Number of Biomarkers Including Tumor Protein 53 and HPV During Treatment Phase
timeFrame: Week 2
measure: Summary of Adverse Events by Maximum Toxicity Grade Started During Treatment Phase
timeFrame: Week 1 through Week 6
measure: Summary of Adverse Events by Maximum Toxicity Grade (Grade 3 or Higher) Started During or After the Chemoradiotherapy Phase
timeFrame: Week 10 through 25
measure: Comparison of Overall Response During Treatment Phase Using CT/MRI and PET Information
timeFrame: Week 2 - 4
measure: Comparison of Overall Response During Follow up Phase Using CT/MRI and PET Information
timeFrame: weeks 19 - 25
measure: Summary of Adverse Events Experienced by 15% or More Subjects in Either Treatment Group
timeFrame: Week 1 through 25
measure: Summary of Fatal/Serious Adverse Events During or After Chemoradiotherapy Phase
timeFrame: Week 10 through 25
measure: Summary of Serious Adverse Events During or After Chemoradiotherapy Phase
timeFrame: Week 10 through 25
measure: Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase
timeFrame: Week 10 through 25
measure: Adverse Events (AEs) by Maximum Toxicity Grade 4 During or After Chemoradiotherapy Phase
timeFrame: Week 10 through 25
measure: Adverse Events by Maximum Toxicity Grade 5 During or After Chemoradiotherapy Phase
timeFrame: Week 10 through 25
measure: Relative Change From Baseline of Ktrans Median (1/Min) After 2 - 4 Weeks of Treatment
timeFrame: Baseline, and Week 2 - 4
measure: Relative Change From Baseline of Kep Mean (1/Min) After 2 - 4 Weeks of Treatment
timeFrame: Baseline, and Week 2 - 4
measure: Relative Change From Baseline of Kep Perfused (1/Min) After 2 - 4 Weeks of Treatment
timeFrame: Baseline, and Week 2 - 4
measure: Relative Change From Baseline of Kep Whole (1/Min) After 2 - 4 Weeks of Treatment
timeFrame: Baseline, and Week 2 - 4
measure: Relative Change From Baseline of Ktrans Mean (1/Min) After 2 - 4 Weeks of Treatment
timeFrame: Baseline, and Week 2 - 4
measure: Relative Change From Baseline of Ktrans Perfused (1/Min) After 2 - 4 Weeks of Treatment
timeFrame: Baseline, and Week 2 - 4
measure: Relative Change From Baseline of Ktrans Whole (1/Min) After 2 - 4 Weeks of Treatment
timeFrame: Baseline, and Week 2 - 4
measure: Relative Change From Baseline of IAUC Median (90) After 2 - 4 Weeks of Treatment
timeFrame: Baseline, and Week 2 - 4
measure: Relative Change From Baseline of IAUC Mean (90) After 2 - 4 Weeks of Treatment
timeFrame: Baseline, and Week 2 - 4
measure: Relative Change From Baseline of Perfused IAUC (90) After 2 - 4 Weeks of Treatment
timeFrame: Baseline, and Week 2 - 4
measure: Relative Change From Baseline of Whole IAUC(90) After 2 - 4 Weeks of Treatment
timeFrame: Baseline, and Week 2 - 4
measure: Relative Change From Baseline of Kep Median (1/Min) After 2 - 4 Weeks of Treatment
timeFrame: Baseline, and Week 2 - 4
Other outcomes:
Locations:
city: Caen
country: France
facility: GSK Investigational Site
city: Montpellier Cedex 5
country: France
facility: GSK Investigational Site
city: Villejuif Cedex
country: France
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Bangalore
country: India
facility: GSK Investigational Site
city: Thiruvananthapuram
country: India
facility: GSK Investigational Site
city: Lima
country: Peru
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials, MD, PhD
role: STUDY_DIRECTOR
References: