Phase I/II study on induction chemotherapy followed by chemoradiation with or without lapatinib, a dual EGFR/ErbB2 kinase inhibitor, in patients with locally advanced resectable larynx and hypopharynx squamous cell carcinoma

• Conditions: locally advanced resectable larynx and hypopharynx squamous cell carcinoma; MedDRA version: 8.1Level: LLTClassification code 10060121Term: Squamous cell carcinoma of head and neck

• Registration Number: EUCTR2006-002667-33-BE
• Lead Sponsor: European Organisation for Research and Treatment of Cancer

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-03-23
• Last Update Posted: 7 October 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Histologically proven newly diagnosed laryngeal and hypopharyngeal
cancer.
? Patients with T3 or T4 larynx or T2, T3 T4 hypopharynx
? Nodal status must be N0, N1, N2a, N2b, N2c and N3
? Patients must consent to access of their biological material for EGFR
status and must consent to PET
? Patient must have tumors amenable to surgery
? Absence of distant metastasis
? No prior treatment for head and neck cancer
? Age above 18
? WHO PS 0-2
? Normal hematological functions: neutrophils superior or equal to 1.5
x109 cells/l, platelets superior or equal to 100 x109 cells/l.
? Normal liver functions: bilirubin < 1.5 times the upper limit of the
normal range; alkaline phosphatase and transaminases inferior to 2.5 the
upper limit of the normal range.
? Serum creatinine lower than or equal to 150 µmol/l (< 1.7mg/dl).
? Patients should be able to swallow oral agents.
? Patients having normal cardiac function (LVEF assessed by MUGA or
ECHO), clinically satisfactory 12 lead ECG, and in the past 6 months
no serious cardiac illness or medical condition including but not
confined to:
- History of documented congestive heart failure (CHF)
- High-risk uncontrolled arrhythmias
- Angina pectoris requiring antianginal medication
- Clinically significant valvular heart disease
- Evidence of transmural infarction on ECG
- Poorly controlled hypertension (e.g. systolic >180mm Hg or diastolic
greater than 100mm Hg)
? Drugs and several HERBAL CONSTITUENTS (e.g. bergamottin and
glabridin), which are inducers or inhibitors of CYP3A4 must not be
taken within 10 days prior to initiation of treatment and are prohibited
while the patient is being treated with lapatinib (a detailed list is
provided in chapter 5)
? All patients (male and female) must use effective contraception
methods according to CPMP/ICH/286/95 if of reproductive potential
(e.g. implants, injectables, combined oral contraceptives, IUDs, sexual
abstinence or vasectomised partner). Contraception methods should be used from 2 weeks before the start of treatment and until 4 weeks after the end of treatment.
- Females must not be pregnant (negative serum pregnancy test at entry) or lactating
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years)
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years)
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Not provided

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary end point(s): The primary endpoint will be to determine the maximal tolerated dose (MTD), dose limiting<br>toxicities (DLTs), and recommended dose of lapatinib. DLTs will be documented during first and<br>second cycles of neoadjuvant chemotherapy to allow dose escalation but determination of<br>recommended dose will be documented with both DLT rules and based on 80% dose intensity (rule of 80% dose intensity will be applied during the whole treatment duration from the start of<br>neoadjuvant chemotherapy to the end of concomitant chemoradiation).;Main Objective: The primary objective is to determine the maximal tolerated dose, and<br>recommended dose for phase II of lapatinib when concomitantly<br>administered with neoadjuvant chemotherapy with TPF ( Taxotere,<br>Cisplatin, 5-FU) followed by chemoradiation with carboplatin.;Secondary Objective: