A PHASE III RANDOMISED, STRATIFIED, PARALLEL-GROUP, MULTI-CENTRE, COMPARATIVE STUDY OF ZD1839 (IRESSA®) 250 MG AND 500 MG VERSUS METHOTREXATE FOR PREVIOUSLY TREATED PATIENTS WITH SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK - IMEX

• Register: EUCTR
• Last refreshed on: 16 November 2015
• Main ID: EUCTR2004-002662-38-LT
• Date of registration: 29/11/2004
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: A PHASE III RANDOMISED, STRATIFIED, PARALLEL-GROUP, MULTI-CENTRE, COMPARATIVE STUDY OF ZD1839 (IRESSA®) 250 MG AND 500 MG VERSUS METHOTREXATE FOR PREVIOUSLY TREATED PATIENTS WITH SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK - IMEX
• Scientific title: A PHASE III RANDOMISED, STRATIFIED, PARALLEL-GROUP, MULTI-CENTRE, COMPARATIVE STUDY OF ZD1839 (IRESSA®) 250 MG AND 500 MG VERSUS METHOTREXATE FOR PREVIOUSLY TREATED PATIENTS WITH SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK - IMEX
• Date of first enrolment: 09/03/2005
• Target sample size: 477
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-002662-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: partially blinded - doses of ZD1839 will be blinded to each other If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Estonia, Latvia, Lithuania

Key inclusion & exclusion criteria

Inclusion criteria:
1.provision of informed consent
2.female or male patients aged 18 years and over
3.histological confirmation of evidence of squamous cell carcinoma of the head and neck diagnosed by biopsy or fine needle aspiration (FNA) at initial presentation
4.Stratum A:
Patients must have had radiotherapy or chemoradiotherapy as primary treatment and must have received at least a course of 2 cycles of platinum-based chemotherapy for recurrent disease and response to the most recent course of platinum-based chemotherapy must have been either progressive disease (radiologically documented) or stable disease (radiologically documented) after at least 2 cycles of platinum based chemotherapy.
or
Stratum B. Patients whose tumours have progressed after primary treatment with radiation or chemoradiation and are considered unsuitable for platinum-based chemotherapy, due to performance status 2, decreased creatinine clearance, cardiac status or refusal of such chemotherapy (by the investigator) due to potential toxicity.
5.no prior anti-EGFR or methotrexate therapy
6.life expectancy ³8 weeks
7.WHO Performance Status 0, 1 or 2

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1.carcinomas of the post-nasal space, thyroid, sinus or salivary gland tumours
2.isolated recurrent disease that may be amenable to local therapy eg, surgical intervention or radiation therapy
3.known severe hypersensitivity to ZD1839, methotrexate or any of the excipients of these products
4.other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ
5.any unresolved chronic toxicity greater than CTC grade 2 from previous anticancer therapy
6.any third space accumulation of fluid (oedema, effusion, ascites)
7.absolute neutrophil counts =1.5 x 109/L or platelets =100 x 109/L
8.serum bilirubin =1.25 times the upper limit of the reference range (ULRR)
9.alanine aminotransferase (ALT/SGPT) or aspartate aminotransferase (AST/SGOT) > 2.5 times the ULRR if no demonstrable liver metastases, or > 5 times the ULRR in the presence of liver metastases
10.evidence of clinically active interstitial lung disease (patients with chronic stable radiographic changes who are asymptomatic need not be excluded)
11.as judged by the investigator, any evidence of severe or uncontrolled systemic disease (eg, unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)
12.evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study
13.pregnancy or breast feeding (women of child-bearing potential)
14.concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, or St John’s Wort
15.treatment with a non-approved or investigational drug within 30 days before Day 1 of study treatment
16.intra-cerebral metastases unless diagnostic imaging demonstrates no peritumoural oedema or progression since last scan (with at least 4-6 weeks between scans), the patient does not require corticosteroids, and the patient is asymptomatic from the metastases
17.concurrent treatment with other experimental drugs and/or anticancer agents



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

squamous cell carcinoma of the head and neck

Intervention(s)

Product Name: Iressa (gefitinib)
Product Code: ZD1839
Pharmaceutical Form: Tablet
INN or Proposed INN: gefitinib
Other descriptive name: Iressa
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 250-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Trexan
Product Name: methotrexate
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: methotrexate
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: range
Concentration number: 40-60

Primary Outcome(s)

Primary end point(s): Patients will receive one dose of ZD1839 daily until disease progression or discontinuation from the study for any other reason (see section 3.3.5 of protocol). All patients will be followed for survival.

Secondary Objective: 1. To compare ZD1839 (250 mg and 500 mg) versus methotrexate in terms of symptom improvement
2. To compare ZD1839 (250 mg and 500 mg) versus methotrexate in terms of overall objective tumour response (CR + PR) using RECIST criteria
3. To compare ZD1839 (250 mg and 500 mg) versus methotrexate in terms of safety and tolerability
4. To assess Quality of Life of patients treated with ZD1839 (250 mg and 500 mg) versus methotrexate

Main Objective: To compare ZD1839 (250 mg and 500 mg) versus methotrexate in terms of overall survival

Secondary ID(s)

ZD1839IL/0704

2004-002662-38-LV