A Phase II Randomised, Double-blind, Placebo-controlled, Multicentre Comparative study of ZD1839 250 mg or 500 mg (Iressatm) given either continuously or concomitantly with cisplatin plus radiotherapy for the treatment of patients with previously untreated unresected late stage III/IV non-metastatic head and neck squamous cell carcinoma

• Register: EUCTR
• Last refreshed on: 7 October 2014
• Main ID: EUCTR2004-000358-21-BE
• Date of registration: 31/08/2005
• Prospective Registration: No
• Primary sponsor: AstraZeneca AB
• Public title: A Phase II Randomised, Double-blind, Placebo-controlled, Multicentre Comparative study of ZD1839 250 mg or 500 mg (Iressatm) given either continuously or concomitantly with cisplatin plus radiotherapy for the treatment of patients with previously untreated unresected late stage III/IV non-metastatic head and neck squamous cell carcinoma
• Scientific title: A Phase II Randomised, Double-blind, Placebo-controlled, Multicentre Comparative study of ZD1839 250 mg or 500 mg (Iressatm) given either continuously or concomitantly with cisplatin plus radiotherapy for the treatment of patients with previously untreated unresected late stage III/IV non-metastatic head and neck squamous cell carcinoma
• Date of first enrolment: 25/11/2004
• Target sample size: 224
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-000358-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Belgium, Czech Republic

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provision of written informed consent
2. Female or male patients aged 18 years and over
3. Patients must have measurable disease according to RECIST
4. Presence of stage III or IVA (Appendix L) squamous cell carcinoma of the head and neck confirmed histologically by biopsy or by fine needle aspiration at the time of diagnosis
5. No previous surgery to the tumour except for biopsy and not scheduled for surgery
6. No previous chemotherapy or radiotherapy for any neoplasm/tumour
7. No previous anti-EGFR therapy
8. Life expectancy ³12 weeks.
9. World Health Organisation (WHO) Performance Status of 0 or 1

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) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Buccal mucosal carcinomas and post-nasal space (nasopharyngeal carcinoma), thyroid, sinus or salivary gland tumours and Grade III laryngeal carcinoma
2. Early stage III cancers (T1N1 or T2N1), Extensive disease (T4b) or metastatic disease (M1)
3. Disease invading the mandible
4. The presence of simultaneous primary tumours
5. Known severe hypersensitivity to ZD1839 or any of the excipients of this product
6. Known severe hypersensitivity to cisplatin or any of the excipients of this product
7. Any evidence of clinically active interstitial lung disease (patients with chronic, stable, radiographic changes who are asymptomatic need not be excluded)
8. Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ
9. Absolute neutrophil counts (ANC) £1.0 x 109/litre (L) or platelets £100 x 109/L
10. Serum bilirubin ³3 times the upper limit of the reference range (ULRR)
11. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 times the ULRR
12. Calculated creatinine clearance (Cockcroft and Gault) £60 ml/min
13. Serum calcium above the ULRR
14. As judged by the investigator, any evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, cardiac, hepatic or renal disease)
15. Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study
16. Pregnancy or breastfeeding.
17. Concomitant use of phenytoin, carbamazepine, barbiturates, rifampicin, amifostine, erythropoietin or St. John’s Wort
18. Concomitant use of CYP3A4 inhibitors (e.g., itraconazole)
19. Treatment with a non-approved or investigational drug within 30 days before
Day 1 of study treatment
20. Evidence of ototoxicity or other neurotoxicity
21. 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

Untreated, unresected late stage III/IV non-metastatic head and neck squamous cell carcinoma

Intervention(s)

Product Name: Iressa (gefitinib)
Product Code: ZD1839
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: gefitinib
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective of the study is to assess the additive effect of ZD1839 250 mg and ZD1839 500 mg (given either concomitantly or as maintenance) over cisplatin plus radiotherapy (RT) in terms of local disease control (progression-free) rate at 2 years.

Secondary Objective: Comparing ZD1839 250 mg and ZD1839 500 mg or placebo:

1. used continuously (concomitantly and for maintenance) with cisplatin plus radiotherapy (RT) in terms of local disease control (progression-free) rate at 2 years.
2. used either concomitantly alone or continuously with cisplatin plus radiotherapy (RT) in terms of local disease control (progression-free) rate at 1 year.
3. used either concomitantly alone or continuously with cisplatin plus radiotherapy (RT) in terms of complete response (CR).
4. used either concomitantly alone or continuously with cisplatin plus radiotherapy (RT) in terms of progression-free survival (PFS).
5. used either concomitantly alone or continuously with cisplatin plus radiotherapy (RT) in terms of safety & tolerability.
6. used either concomitantly alone or continuously with cisplatin plus radiotherapy (RT) in terms of overall survival.

Primary end point(s): Two years after the last patient is randomised

Secondary ID(s)

D7919C00706 (ZD1839IL/0706)

2004-000358-21-CZ