E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
First line treatment of metastatic pancreas CA with AS703026 in combination with gemcitabine and / or after progression under gemcitabine monotherapy second line treatment with AS703026. |
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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 | 10033576 |
E.1.2 | Term | Pancreas carcinoma |
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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 | 10033577 |
E.1.2 | Term | Pancreas carcinoma recurrent |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the anti-tumor activity of AS703026 combined with gemcitabine compared to gemcitabine alone as first line treatment in subjects with metastatic pancreatic adenocarcinoma. During the safety run-in the Maximum Tolerated Dose (MTD) and the recommended dose of AS703026 when combined with gemcitabine in subjects with metastatic pancreatic adenocarcinoma will be determined.
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E.2.2 | Secondary objectives of the trial |
To determine the safety and tolerability of AS703026 combined to gemcitabine in subjects with metastatic pancreatic cancer. To evaluate the anti-tumor activity in each treatment arm in terms of response rate, clinical benefit, overall survival and time to progression. To assess: - the pharmacokinetics (PK) of AS703026 and gemcitabine when given in combination, in subjects with metastatic pancreatic cancer. - changes in pharmacodynamic (Pd) markers (e.g. phospho-ERK in PBMCs). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject fully understands requirements of the trial, is willing to comply with all trial visits and assessments, has provided written informed consent. Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas and availability of tumor sample (archived or fresh biopsy). Evidence of disease (not necessarily measurable disease) as per complete tumor assessment performed within 28 days prior to trial entry/randomization. Age 18 years and older. Women of childbearing potential must have a negative blood pregnancy test at the screening visit. Willingness to avoid pregnancy by using an adequate method of contraception for 2 weeks prior to, during and four weeks after the last dose trial medication as applicable.
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E.4 | Principal exclusion criteria |
Bone marrow impairment as evidenced by hemoglobin < 9.0 g/dL, neutrophil count < 1.5 x 10^9/L, platelets < 100 x 10^9/L. Renal impairment as evidenced by serum creatinine > 1.5 x upper limit of normal (ULN), and/or calculated creatinine clearance < 60 mL/min. Liver function abnormality as defined by total bilirubin > 1.5 x ULN, or AST/ALT > 2.5 x ULN, for subjects with liver involvement AST/ALT > 5 x ULN. Serum calcium > 1 x ULN. History of central nervous system (CNS) metastases, unless certain prerequisites are met. History of difficulty swallowing, malabsorption or other chronic gastro-intestinal disease or conditions that may hamper compliance and/or absorption of the tested product. Eastern Cooperative Oncology Group Performance Status (ECOG PS) greater than 1. Known HIV positivity, active hepatitis C, active hepatitis B or signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such. Prior chemotherapy, other than allowed Extensive prior radiotherapy or prior bone marrow/stem cell transplantation. Prior radiation for local disease management is allowed under certain circumstances. History of any other significant medical disease that might impair the subjects well being or preclude full participation in the trial. Significant cardiac conduction abnormalities and/or pacemaker. Pregnant or nursing female subject. Retinal degenerative disease (hereditary retinal degeneration or age-related macular degeneration), history of uveitis or history of retinal vein occlusion. Known hypersensitivity to the AS703026 or gemcitabine. Participation in another clinical trial within the past 28 days. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-Free Survival (PFS), defined as time (in months) from randomization date to date of progression prior to the start of subsequent AS703026 monotherapy, as reported and documented by the Investigator (i.e. radiological progression per RECIST criteria). The PFS Hazard Ratio (HR) of experimental arm versus control arm will be used in the primary statistical analysis of the main study part. During the safety run-in: Dose-Limiting Toxicity (DLT) using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 | 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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Date of the last dose + 28 days (i.e. last patient last visit) or - in order to satisfy the statistical evaluation parameters for analysis of the primary endpoint - when at least 2/3 events for survival have been observed, which ever comes last. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |