E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
duodeno-pancreatic (neuro) endocrine tumors and different pituitary diseases (Nelsonメs syndrome, non-functioning adenoma, TSH-adenoma,Gonadotroph adenoma, and PRL-adenoma) |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10035098 |
|
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 effect of SOM230 s.c. in patients with rare life threatening diseases as follows: Biochemical tumor markers for those patients with duodeno-pancreatic (neuro) endocrine tumors (insulinoma, glucagonoma and VIPoma) and Thyrotropin-pituitary adenoma (TSH-adenoma) ユ Tumor response for those patient with pituitary diseases (Nelsonメs syndrome, nonfunctioning pituitary adenoma, Gonadotroph adenoma, and Prolactin-pituitary adenoma (PRL-adenoma) and gastrinoma. |
|
E.2.2 | Secondary objectives of the trial |
To assess the overall safety of SOM230 s.c. in this diverse population ユ To assess the effect of SOM230 s.c. on disease related symptoms (Post-text supplement 3) ユ To assess the effect of SOM 230 s.c. on biochemical tumor markers for Nelsonメs syndrome, Gonadotroph- adenoma, PRL-adenoma and gastrinoma ユ To assess the effect of SOM230 s.c. on tumor response for duodeno-pancreatic (neuro)endocrine tumors (exception: gastrinoma) and TSH- adenoma ユ To assess the effect of SOM230 s.c. on Quality of Life (Post-text upplement 2) ユ To assess pharmacodynamic effects of SOM230 s.c. at doses of 600 ᄉg and 900 ᄉg administered on a b.i.d. schedule in patients with duodeno-pancreatic (neuro)endocrine tumors and different pituitary diseases (Nelsonメs syndrome, non-functioning adenoma,TSH-adenoma, Gonadotroph adenoma, and PRL-adenoma) ユ To assess the single and multiple dose pharmacokinetics of SOM230 s.c. at doses of 600 ᄉg and 900 ᄉg administered on a b.i.d. (pls see protocol) |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Male or female patients >= 18 years ユ Patients with pituitary disease or duodeno-pancreatic (neuro) endocrine tumors diagnosed with the criteria described in Table 5-1 ユ Karnofsky status >60 ユ Patients must have had the following washout periods: octreotide LAR - 8 weeks, octreotide s.c. - 48 hours, lanreotide (Autogel) - 8 weeks, lanreotide SR - 4 weeks. ユ Written informed consent obtained prior to any screening procedures ユ Female patients of child bearing potential who have not undergone clinically documented total hysterectomy and/or ovariectomy, or tubal ligation must agree to use barrier contraception throughout the course of the study, and for 30 days after the study has ended. Male patients are required to use a condom throughout the study and for at least 30 days following study completion. Specific inclusion criteria by tumor type, refer to Table 5-1: ユ Insulinoma ユ 72 hour fast: glycopenic symptoms, low glycemia (3.3 mmol/l and inappropriately high level of insulinemia) ユ Gastrinoma ユ Symptoms not controlled by Proton Pump Inhibitor (PPI) and/or tumor progression. PPI could be continued throughout the study. ユ PRL-adenoma ユ Macroadenoma (adenoma > 10mm) not controlled by dopamine agonist. Dopamine agonist could be continued throughout study. ユ Non-functioning pituitary adenoma, Gonadotroph adenoma, PRL-adenoma and Nelsonメs syndrome ユ Prior radiotherapy received must be at least 12 months before start of study |
|
E.4 | Principal exclusion criteria |
Patients with active gall bladder disease ユ Poorly controlled diabetes mellitus as indicated by the presence of HbA1c > 9% (Not applicable for glucagonoma patients). ユ Patients with additional active malignant diseases within the last five years (with the exception of correctly treated basal cell carcinoma or carcinoma in situ of the cervix) ユ Patients who have any current or prior medical condition that may interfere with the conduct of the study or the evaluation of its results in the opinion of the Investigator or the Sponsorメs Medical Monitor ユ Female patients who are pregnant or lactating, or are of childbearing potential and not practicing a medically acceptable method for birth control. Patients who have participated in any clinical investigation with an investigational drug within 30 days prior to dosing ユ Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will be unable to complete the entire study |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary assessments of activity of SOM230 will be performed with biochemical tumor marker determinations or tumor response, as applicable for each tumor type, which will be collected throughout the study to determine response assessed by tumor marker response at 3 and 6 months. Biochemical tumor marker responses will be defined as good response (>50% decrease from baseline of tumor marker or normalization within normal range), partial response (>20% decrease from baseline of tumor marker), no change (<=20% decrease or increase from baseline of tumor marker), as compared to baseline. Tumor response will be assessed by Computer Tomography (CT) scan or Magnetic Resonance Imaging (MRI) at 3 and 6 months for duodeno-pancreatic (neuro)-endocrine tumors and pituitary disease. Methodology used to assess eligibility will be used throughout the study for response determination. Tumor response will be measured using RECIST criteria for duodeno-pancreatic (neuro) endocrine tumors, (Post-text supplement 1) and percentage of tumor volume reduction for pituitary tumors, with response defined as >=20% decrease from baseline. Patients will be assessed for safety and efficacy, and patient reported outcomes on Quality of Life. Pharmacokinetics will also be assessed. In order to determine the secondary pharmacokinetic effects of SOM230, serum plasma levels will be collected at various time points throughout the study. The associated disease-related symptoms present at baseline will be followed throughout the study. Examples of the disease-related symptoms associated with each tumor type are noted in Table 5-1. QoL information will be collected via the validated Memorial Symptom Assessment Scale (MSAS), and Karnofsky performance status. |
|
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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
studio in aperto, pilota di fase II |
|
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.8.5 | 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 |
|
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 |