E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Histologically or cytologically confirmed solid cancer of any pathology or adenocarcinoma of the pancreas |
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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 | 10065147 |
E.1.2 | Term | Malignant solid tumor |
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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 | 10052747 |
E.1.2 | Term | Adenocarcinoma pancreas |
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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 |
Phase I part: - To determine the maximum tolerated dose (MTD) and recommended dose (RD) of human L19IL2 in combination with gemcitabine in advanced solid tumour patients for whom gemcitabine is a suitable therapy according to the discretion of the principal investigator or in relapsed/refractory advanced pancreatic cancer patients after 1st line gemcitabine-containing therapy. Phase II part: - To investigate the anti-cancer activity of L19IL2 in combination with gemcitabine as measured by Clinical Benefit Response in chemotherapy-naïve patients with advanced pancreatic cancer.
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E.2.2 | Secondary objectives of the trial |
Phase I part: - To investigate the pharmacokinetic properties of L19IL2 and gemcitabine when given in combination. - To investigate induction of human anti-fusion protein antibody (HAFA) levels. - To investigate early signs of anti-tumor activity of L19IL2 combined with gemcitabine in terms of objective response rate, median overall survival and survival at 12 months. Phase II part: - To investigate safety and tolerability of the combination treatment of L19IL2 and gemcitabine. - To assess the presence of anti-fusion protein antibodies in treated patients. - To investigate the objective response rate, median progression-free survival, and median overall survival of L19IL2 in combination with gemcitabine.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Histologically or cytologically confirmed solid cancer of any pathology or adenocarcinoma of the pancreas with evidence of locally advanced (non resectable Stage II or III) or metastatic disease (Stage IV; Appendix B). Karnofsky performance status 60-100% for phase 1 and >50 and <80% for phase II (ECOG performance status ≤2). Patients aged >=18 years. Sufficient hematologic, liver and renal function:
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E.4 | Principal exclusion criteria |
Presence of active infections (e.g. requiring antibiotic therapy) or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study. Presence of known brain metastases. Known to have a second uncontrolled cancer of other primary origin within the last 5 years. Chronic active hepatitis or active autoimmune diseases. History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris. Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria). Irreversible cardiac arrhythmias requiring permanent medication. Uncontrolled hypertension. Ischemic peripheral vascular disease (Grade IIb-IV). Severe rheumatoid arthritis. Severe diabetic retinopathy. Recovery from major trauma including surgery within 4 weeks of administration of study treatment. Known history of allergy to IL2, gemcitabine, or other intravenously administered human proteins/peptides/antibodies. Chemotherapy (standard or experimental) or radiation therapy within 4 weeks of the administration of study treatment for patients recruited to the phase I part of the study. Prior chemotherapy or radiation therapy or treatment with an investigational study drug for patients recruited to the fixed-dose part (phase II) of the study. Previous in vivo exposure to monoclonal antibodies for biological therapy in the 6 weeks before administration of study treatment. Growth factors or immunomodulatory agents within 7 days of the administration of study treatment.
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E.5 End points |
E.5.1 | Primary end point(s) |
To determine the maximum tolerated dose (MTD) and recommended dose (RD) of human L19IL2 in combination with gemcitabine in advanced solid tumour patients for whom gemcitabine is a suitable therapy according to the discretion of the principal investigator or in relapsed/refractory advanced pancreatic cancer patients after 1st line gemcitabine-containing therapy. |
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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 | 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) | Yes |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Evaluation of the MTD and RD of a combination of L19IL2 and gemcitabine |
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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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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 | |
E.8.9.1 | In the Member State concerned months | 31 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 31 |