E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally Advanced or Metastatic Gastric Cancer or Adenocarcinoma of the Gastro-oesophageal Junction |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063916 |
E.1.2 | Term | Metastatic gastric cancer |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10017758 |
E.1.2 | Term | Gastric cancer |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066896 |
E.1.2 | Term | HER-2 positive gastric cancer |
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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 |
Effect on progression free survival defined as the time measured from the day of registration to first progression or death. |
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E.2.2 | Secondary objectives of the trial |
Toxicity Overall survival, defined as the time from registration to death Response rate defined as the percentage of partial and complete responses Duration of response defined as time from response to first progression Translational research on pharmacogenomic and biological factors that may predict treatment response. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically confirmed adenocarcinoma of the stomach or gastro-oesophageal junction with inoperable locally advanced or recurrent and/or metastatic disease not amenable to curative therapy. 2. Measurable disease, according to the Response Evaluation Criteria in Solid Tumours (RECIST), assessed using imaging techniques (CT or MRI) 3. ECOG Performance status 0, 1 or 2 4. Life expectancy of at least 3 months 5. Male or female age ≥ 18 years 6. Signed informed consent 7. Assessment of HER2 status (primary tumour or metastasis) by the central laboratory prior to initiation of study treatment (Dual SISH, Ventana). 8. Able to swallow and retain oral medication. |
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E.4 | Principal exclusion criteria |
1. Previous chemotherapy for advanced/metastatic disease (prior peri-operative chemotherapy is allowed if at least 6 months has elapsed between completion of this therapy and enrolment into the study) 2. Previous radiotherapy on the abdomen 3. Other malignancy within the last 5 years, except for carcinoma in situ of the cervix, or basal cell carcinoma 4. Patients with active (significant or uncontrolled) gastrointestinal bleeding 5. Residual relevant toxicity resulting from previous therapy (with the exception of alopecia), e.g. neurological toxicity ≥ grade 2 NCI-CTCAE 6. Creatinin clearance <50 mL/min 7. Neutrophil count <1.5 × 109/L, or platelet count <100 × 109/L 8. Serum bilirubin >1.5 × upper limit of normal (ULN); or, AST or ALT >2.5 × ULN (or > 5 × ULN in patients with liver metastases); or, alkaline phosphatase >2.5 × ULN (or >5 × ULN in patients with liver metastases, or >10 × ULN in patients with bone but no liver metastases); or, albumin <25 g/L 9. Known dihydropyrimidine dehydrogenase (DPD) deficiency. 10. History of documented congestive heart failure; angina pectoris requiring medication; evidence of transmural myocardial infarction; poorly controlled hypertension (systolic BP >180 mmHg or diastolic BP >100 mmHg); clinically significant valvular heart disease; or high risk uncontrollable arrhythmias. 11. Patients with dyspnoea at rest due to complications of advanced malignancy or other disease, or who require supportive oxygen therapy. 12. Patients receiving chronic or high dose corticosteroid therapy. (Inhaled steroids and short courses of oral steroids for anti-emesis or as an appetite stimulant are allowed) 13. Major surgery within 4 weeks of start of study treatment, 14. Known hypersensitivity to any of the study drugs 15. History or clinical evidence of brain metastases 16. Serious uncontrolled systemic intercurrent illness, e.g. infections or poorly controlled diabetes 17. Positive serum pregnancy test in women with childbearing potential 18. Subjects with reproductive potential not willing to use an effective method of contraception 19. Any investigational drug treatment within 4 weeks of start of study treatment 20. Radiotherapy within 4 weeks of start of study treatment (2 week interval allowed if palliative radiotherapy given to bone metastastic site peripherally and patient recovered from any acute toxicity) 21. Therapeutic use of oral coumarin-derived or LMWH anticoagulants or NSAIDs. 22. Continuous use of immunosuppressive agents (for the use of corticosteroids see #12).
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression free 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 | Yes |
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 | No |
E.6.11 | Pharmacogenomic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 12 |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |