E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
locally advanced or metastatic inoperable adenocarcinoma of the pancreas with no prior chemotherapy |
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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 | 10033606 |
E.1.2 | Term | Pancreatic cancer non-resectable |
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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 |
For Phase II • To assess the Disease Control Rate DCR (CR+PR+SD) For Phase III Primary endpoint: • To compare overall survival (OS)
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E.2.2 | Secondary objectives of the trial |
For Phase II • To assess the 1-year survival • To assess toxicity For Phase III • To compare progression-free survival time (PFS). • To compare objective response rate (ORR) • To compare quality of life (QοL) • To compare safety
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Adult male or female 18-70 years old. • Histologically or cytologically confirmed diagnosis of locally advanced or metastatic inoperable adenocarcinoma of the pancreas • Presence of at least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors. (RECIST, see Appendix II). • WHO performance status (PS) 0-1 (Appendix I). • Life expectancy of at least 3 months. • At least 4 weeks since prior major surgery, with full recovery from all side effects. • Adequate bone marrow function (defined as peripheral absolute granulocyte count > 2000/mm3 and platelet count ≥ 140000/mm3). • Adequate liver function (bilirubin ≤ 2 mg/dl, SGOT or SGPT no greater than 2.5 x ULN or 4 x ULN in case of hepatic metastasis). • Adequate renal function (creatinine ≤ 1.5 mg/dl, creatinine clearance ≥ 60ml/min). Clearance to be measured after 24-hour urine collection, or calculated by the following formulas: CrClmale=[(140-age)*(wt. as kg)]/[(serum Cr mg/dl)x72] CrClfemale=0.85*(CrClmale) • Patients must understand and sign an informed consent document that explains the neoplastic nature of his/her disease, the procedures to be followed, the experimental nature of the treatment, alternative treatments, and potential risks and toxicities.
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E.4 | Principal exclusion criteria |
• Other malignancy within the past 5 years, except malignancies with <5% probability of recurrence, curatively treated squamous or basal cell skin carcinoma, or in situ carcinoma of the cervix. • Known allergy to any of the study drug components. • Prior chemotherapy, radiotherapy or investigational drug treatment for pancreatic cancer. • Known brain metastases. • Malnutrition (>25% weight loss). • Recent history of myocardial infarction (within the last 6 months), history of congestive heart failure, congenital heart disease, or ventricular arrhythmias. • Known Hepatitis B or C, or AIDS. • Known underlying immune deficiency or history of autoimmune diseases (e.g. autoimmune neutropenia, hemolytic anaemia or thrombocytopenia, systemic lupus erythematosus, Sjögren syndrome, Addison’s disease, scleroderma, myasthenia Gravis, Goodpasture’s syndrome, Hashimoto’s thyroiditis or other diseases of autoimmune origin). • Pregnant or lactating women. For women of childbearing age an initial negative pregnancy test and usage of a reliable contraceptive method during and for 3 months after study participation is a requirement. • Any medical, psychiatric or social condition that would preclude informed consent (e.g. homeless patients or with dementia). • Patients for whom compliance with the protocol is doubtful.
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase ΙΙ: • Disease Control Rate (DCR) is defined as the sum of Complete Response (CR) plus Partial Response (PR) plus Stable Disease (SD) at week 9 of treatment. Evaluation of response is based on the Response Evaluation Criteria in Solid Tumors (RECIST, see Appendix II), with confirmation at 4 weeks.
DCR will be used instead of Objective Response Rate (ORR=Complete Response+Partial Response), as it is a more helpful measure in cancers difficult to evaluate or with only minor response to treatment, as is the case for pancreatic cancer. Although DCR at first post-baseline disease evaluation may be more sensitive to initial differences in tumor growth rate, most bibliographic references use the specific time, which was therefore chosen for the current study.
Phase III: • Overall Survival (OS) is defined as the time from randomisation until death from any cause.
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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) | 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 | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 | 5 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 10 |