E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with esophagus or gastric cancer and who are platinum resistant and non-resectabel |
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E.1.1.1 | Medical condition in easily understood language |
Patients with cancer of the esophagus or stomach |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017758 |
E.1.2 | Term | Gastric cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 evaluate the efficacy of bevacizumab and irinotecan in combination compared to irinotecan alone in patients with esophagus, cardia or gastric cancer.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with histologically proven esophagus, cardia og gastric adenocarcinoma, non-resectable or metastatic disease.
2. Progression after first line treatment with platinum containing chemotherapy. Patients who progress after completed adjuvant platinum containing chemotherapy can also be included in the study.
3. Patient withy measurable or non-measurable disease.
4. Age ≥ 18 yearts.
5. Performance status (WHO) ≤ 0-1.
6. Neutrophil count (ANC) ≥ 1.5 x 109/L og platelets ≥ 100 x 109/L.
7. Normal liverfunction: Bilirubin < 1.5 x UNL (upper normal limit), ASAT and/or ALAT ≤ 3 x UNL (no upper limit for ASAT and ALAT in case of livermetastases).
8. Creatinin clearence ≥ 30 ml/min (Cockroft-Gault formular).
9. INR og APTT ≤ normal limit.
10. Signed consent form.
11. Expected lifetime > 3 months.
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E.4 | Principal exclusion criteria |
1. Patienter der er ude af stand til at følge behandling og evalueringsplan.
2. Enhver tilstand eller terapi som efter investigators mening udsætter patienten for en risiko eller påvirker forsøgets formål (f.eks. AMI indenfor 1 år, aktive infektioner).
3. Gravide eller ammende kvinder. Hos fertile kvinder sikres dette med negativ graviditetstest eller anvendelse af sikker antikonception som defi¬neret i Sundhedsstyrelsens vejledning under hele forsøgsbehandlingen og mindst 3 måneder efter afsluttet behandling.
4. Patienter der tidligere har modtaget behandling med enten bevazicumab eller irinotecan.
5. Kendt hypersensitivitet overfor en eller flere af komponenterne i behand¬lingen.
6. Anden aktiv malign sygdom.
7. Klinisk betydende perifer karsygdom.
8. Tegn på blødningsforstyrrelse eller koagulopati.
9. Større kirurgiske indgreb eller traume inden de sidste 28 dage før behandlingsstart eller forventning om dette under behandlingen.
10. Mindre kirurgiske indgreb, finnåls- eller grovnåls-biopsi inden for de sidste 7 dage før behandlingsstart.
11. Tidligere kendt abdominal fistel, gastrointestinal perforation eller intra-abdominal abscess inden for 6 måneder før behandlingsstart.
12. Kendt HIV, Hepatitis B eller Hepatitis C.
13. Proteinuri ≥ grad 2.
14. Blodtryk > 150/100.
15. Behov for terapeutisk anti-koagulation ved behandlingsstart.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint is progression free survival. |
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E.5.2 | Secondary end point(s) |
Secondary endpoints:
• Toxicity grade 2-5 according ot NCI-CTCAE 4.0
• Survival (OS)
• Response rate (RR) according to RECIST 1.1
• Correlation betweend the efficacy of the treatment and the expression of potential tumor markers
• Quality of life
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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 | 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) | 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 | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
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 | 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 | No |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 | No |
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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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 |