E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Oesophageal cancer (adenocarcinoma and squamous cancers). |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001141 |
E.1.2 | Term | Adenocarcinoma |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10041824 |
E.1.2 | Term | Squamous cell carcinoma of esophagus |
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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 assess whether gefitinib will improve overall survival in patients with oesophageal cancer when compared to a placebo. |
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E.2.2 | Secondary objectives of the trial |
* To assess the toxicity of gefitinib monotherapy in oesophageal cancer patients * To assess whether gefitinib will have a significant positive or negative impact upon quality of life compared with placebo * To assess the impact gefitinib will have on progression-free survival compared with placebo * To identify if there are genetic signatures associated with benefit. (This will be done in a translational research project [HANDEL] as a separate protocol)
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The original design of COG included collection of tissue samples for the substudy HANDEL (Histological Assessment Determining EpitheliaL response). This however will now be done directly through HANDEL. Therefore patients entering COG will no longer have the option to consent for tissue samples to be collected for future research. Patients can still do this via HANDEL which will run as a separate trial if the site chooses to participate. This decision came about as the sponsorship of HANDEL moved from the University of Oxford to Queen Mary University in London. It was decided that the tissue samples should be collected directly through HANDEL instead of via COG to simplify the process. |
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E.3 | Principal inclusion criteria |
INCLUSION CRITERIA
1. Age ≥ 18 years 2. Histologically proven adenocarcinoma, squamous cell cancer or poorly differentiated epithelial malignancy 3. Oesophageal cancers or Type I and type II junctional tumors 4. Failure after previous chemotherapy. Treatment not to start until at least 6 weeks from the last day of chemotherapy (including oral) 5. WHO Performance Status 0, 1 or 2 6. Measurable or evaluable disease by CT scan 7. Able to take tablets (whole or dispersed) 8. Patients with brain metastases must be stable and have received cranial irradiation prior to entry
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E.4 | Principal exclusion criteria |
EXCLUSION CRITERIA
1. More than 2 previous chemotherapy regimens and 1 chemoradiation course. 2. Presence of previous or other malignancy likely to confound results or interfere with gefitinib therapy 3. Medical condition considered to interfere with the safe participation in the trial 4. Radiotherapy to site of measurable or evaluable disease in the last 4 weeks 5. Pregnancy 6. Sexually active patients of child-bearing potential not using adequate contraception* (male and female) [post menopausal women must have been amenorrheic for at least 12 months to be considered as having non-child-bearing potential] 7. Serum bilirubin greater than 3 times the upper limit of reference range (ULRR) 8. Aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT) ≥ 2.5 x ULN if no demonstrable liver metastases (or >5 x in presence of liver metastases) 9. Any evidence of clinically active Interstitial Lung Disease (ILD) (patients with chronic, stable, radiographic changes who are asymptomatic need not be excluded) 10. Known severe hypersensitivity to gefitinib or any of the excipients of this product 11. On other cytotoxic chemotherapy, immunotherapy, hormonal therapy (excluding contraceptives and replacement steroids) or experimental medications
* For female trial participants: birth control pills, approved contraceptive implant, spermicidal foam and condoms, intrauterine device, or prior tubal ligation. For male trial participants: condoms and spermicidal foams or prior vasectomy.
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E.5 End points |
E.5.1 | Primary end point(s) |
PRIMARY OUTCOME MEASURE
Overall survival where length of survival is defined in whole days, as the time from randomisation into the trial to death from any cause; for those patients who are not observed to die during the course of the trial, the length of survival will be censored at the last known follow-up date. Follow-up occurs at 4, 8, 12 and 16 weeks after start of treatment and then every eight weeks.
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
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 | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 50 |
E.8.5 | The trial involves multiple Member States | No |
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 | Yes |
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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Recruitment is expected to take 18 months. The trial will close after the last recruited patient has been followed up for six months and 389 events have occurred. This means that all patients will be followed up for at least 6 months, but allows follow-up to continue for longer if the number of required events (deaths) has not been reached. The trial will not end before the 6 months even if the number of events has been reached early.
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |