E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
squamous cell carcinoma of the head and neck |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare ZD1839 (250 mg and 500 mg) versus methotrexate in terms of overall survival |
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E.2.2 | Secondary objectives of the trial |
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
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal 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
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E.4 | Principal 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
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
partially blinded - doses of ZD1839 will be blinded to each other |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |