E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
locally advanced, unresectable or metastatic pancreatic cancer |
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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 | 10033611 |
E.1.2 | Term | Pancreatic carcinoma non-resectable |
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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 |
Compare the overall survival (OS) of patients receiving gemcitabine plus AG 013736 versus gemcitabine plus placebo. |
|
E.2.2 | Secondary objectives of the trial |
Compare the progression free survival (PFS) of patients in each arm Compare the objective response rate (ORR) of patients in each arm Estimate the duration of response (DR) of patients in each arm Evaluate the safety and tolerability of AG 013736 plus gemcitabine Compare the health related quality of life (HRQOL), pain ratings, and health status of patients in each arm as measured by the European Organization for the Research and Treatment of Cancer, Quality of Life Questionnaire Core 30 (EORTC QLQ C30) and Pancreatic 26 (PAN26) (see Appendix A), BPI sf (see Appendix B), and EQ 5D (see Appendix C) Conduct population pharmacokinetic analysis using AG 013736 plasma concentrations |
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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 |
ALTRI SOTTOSTUDI: Farmacogenomica
|
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E.3 | Principal inclusion criteria |
1. Histologically or cytologically confirmed, metastatic or locally-, advanced pancreatic adenocarcinoma not amenable to curative resection. 2. Adequate hepatic and renal function documented within 14 days prior to treatment as documented by: AST and ALT 2.5 x upper limit of normal (ULN), Total bilirubin 1.0 x ULN Serum creatinine 1.5 x ULN or calculated creatinine clearance 60 mL/min Urinary protein <1+ 3. Adequate bone marrow function as defined by: ANC 1500 cells/mm3 platelets 100,000 cells/mm3 hemoglobin 9 g/dL 4. Male or female, age 18 years. 5. ECOG performance status of 0 or 1 (see Appendix D) 6. Life expectancy of ≥12 weeks. 7. Resolution of all acute toxic effects of prior radiotherapy, or surgical procedure to NCI CTCAE Grade 8. No evidence of preexisting uncontrolled hypertension |
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E.4 | Principal exclusion criteria |
1. Prior treatment with any systemic chemotherapy for metastatic disease. 2. Prior adjuvant chemotherapy or radiotherapy <4 weeks before starting the study treatment. 3. Prior treatment with gemcitabine, AG 013736, or other VEGF inhibitors. 4. Current or recent (within 1 month) use of a thrombolytic agent. 5. Central lung lesions involving major blood vessels. 6. History of hemoptysis > œ tsp of bright red blood per day within past 1 week. 7. Gastrointestinal abnormalities 8. Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors 9. Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers. 10. Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis. 11. A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment. 12. Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, deep vein thrombosis or pulmonary embolism. 13. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness. 14. History of a malignancy 15. Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks of treatment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary: OS Overall survival Secondary 1. PFS 2. ORR 3. DR 4. Type, incidence, severity (graded by the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] Version 3.0), timing, seriousness, and relatedness of adverse events, and laboratory abnormalities 5. PROs: EORTC QLQ C30, QLQ PAN26, BPI sf, EQ 5D 6. AG 013736 population pharmacokinetic analysis |
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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 | Yes |
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) | 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 | Yes |
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 | 7 |
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 | 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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |