E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Measurable Locally Advanced and/or Metastatic Adenocarcinoma of the Pancreas |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Safety Objectives:
· Assessment of the safety of biweekly infusions of EndoTAG™-1 and weekly infusions of gemcitabine via: · Incidence and percentage with patients EndoTAG™-1 and gemcitabine related AE · Laboratory abnormalities (hematology, coagulation parameters, clinical chemistry, urine analysis) · Dose reductions, pausing and/or discontinuations of EndoTAG™-1 and/or gemcitabine
Efficacy Objectives:
· Assessment of survival (progression free survival, 6-month survival rate, overall survival) · Tumor response evaluation after 14 applications of EndoTAG™-1 and 7 applications of gemcitabine, i.e. 1 week after last treatment and according to follow-up plan · Clinical Benefit Assessment via Quality of Life (QoL) Scale (EORTC-QoL-C30-Questionnaire, PAN-26-module) · Assessment of clinical status via ECOG Scale |
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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 |
Inclusion Criteria: - Written informed consent - Histologically or cytologically confirmed, pancreatic adenocarcinoma suitable for chemotherapy - Clinical diagnosis of irresectable pancreatic adenocarcinoma ECOG Performance Status 0, 1 or 2 - ≥ 18 years old - Negative pregnancy test (females of childbearing potential) - Willingness to perform double-barrier contraception during study and for 6 months post chemotherapy treatment |
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E.4 | Principal exclusion criteria |
- Cardiovascular disease, New York Heart Association (NYHA) III or IV - History of severe supraventricular or ventricular arrhythmia - History of coagulation or bleeding disorder (PTT > 1.5 x ULN) - Severe pulmonary obstructive or restrictive disease - Diabetic retinopathy - Acute or chronic inflammation (autoimmune or infectious) - Significant active/unstable non-malignant disease likely to interfere with study assessments - Laboratory tests (hematology, chemistry) outside specified limits: - WBC ≤ 3 x 1000/ mm3 - ANC ≤ 1.5 x 1000/mm3 - Platelets ≤ 100.000 / mm3 - Hb ≤ 9.0 g/dl (≤ 5.6 mmol/l) - PT/PTT > 1.5 x ULN - Serum creatinine > 2.0 mg/dl (> 176.8 mmol/l) - AST and/or ALT > 5 x ULN - Alkaline phosphatase > 2 x ULN - Total bilirubin > 2 x ULN - Immunotherapy < 6 weeks prior to enrollment - Any chemotherapeutical treatment for pancreatic adenocarcinoma before enrollment - Any radiotherapy for pancreatic adenocarcinoma before enrollment except for treatment of bone metastases if target lesions are not included in the irradiated field - Major surgery < 4 weeks prior to enrollment - Pregnant or nursing - Investigational medicinal product < 4 weeks of enrollment - HIV history - Hypersensitivity to any component of the EndoTAG™-1 and/or gemcitabine formulations - History of significant liver pathology (other than metastases) - History of malignancy other than pancreatic cancer < 5 years prior to enrollment, except skin cancer treated locally - Vulnerable populations (e.g. subjects incapable of giving consent personally) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy Endpoints
· Median progression free survival (PFS) · 6-month-survival-rate calculated by the rate of patients alive 6 months after start of treatment · Median overall survival (OS) · Tumor Response (CR / PR / SD / PD) after 14 applications of EndoTAG™-1 and 7 applications of gemcitabine (1 cycle) assessed by the following variables: CT/MRI scans, chest X-ray and CA19-9 level kinetics · Clinical Benefit via Assessment of Quality of Life (QoL): EORTC-QoL-C30-Questionnaire + PAN-26-module · Pain assessment (Visual analogue scale = VAS) · ECOG: Number of patients with improvement/ steady state/ deterioration at week 8 compared to baseline · CA 19-9: Number of subjects with increase/no change/decrease between baseline and end of treatment, number of subjects within the normal range at baseline and at end of treatment
Safety endpoints · Adverse Events: Incidence and percentage of patients with treatment emergent AEs · Laboratory Values: Number of clinically significant abnormal laboratory values · Dose variations: Percentage of patients having dose reductions/ pausing or discontinuations of gemcitabine and/or EndoTAG™-1
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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 | 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) | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |