E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
non-functioning pitiutary adenomes |
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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 | 10035079 |
E.1.2 | Term | Pituitary adenoma |
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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 |
NFTs express somatostatin receptors. In vitro, octreotide suppresses intact and glycoprotein subunit secretion from dispersed NFT cells. Although, octreotide has not been effective in vivo, this somatostatin analog binds preferrentially to SSTR2. We propose that SOM230, which binds to all the somatostatin receptor subtypes with high affinity, may be more effective in shrinking the tumor bulk. Study objective is to evaluate the rate of patients responding to SOM230 after 6 months of treatment or during the 6 months treatment period. Response is defined as a decrease of at least 25% decrease in tumor size as compared to baseline.
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or postmenopausal female not receiving HRT; Postmenopausal is defined as a minimum of 12 months absence of menorrhoea. • Age: 18-80 years • The patient must have a clinically demonstrable NFT, with no evidence of acromegaly, Cushing’s disease or prolactinoma as demonstrated by normal IGF-1, normal 24-hour urinary free cortisol levels and normal to moderately elevated prolactin levels (stalk effect, prolactin < 200 ng/ml). A screening TRH test must have been performed to confirm possible gonadotroph hypersecretion. • The patient must have a macroadenoma (>10mm in widest diameter) demonstrated on MRI performed with and without contrast. • Patients must have a normal visual field evaluation by Goldman perimetry. • Hypopituitarism may be present as evidenced by any or all of: a subnormal GH response to Arginine/GHRH testing, low age-and sex matched IGF-1 levels, low TSH, free T3 and Free T4, low estradiol, low LH and FSH levels in postmenopausal female patients or low testosterone, LH and FSH levels in male patients, 8 am serum cortisol < 3µg/dl.
Patients who are diagnosed with hypopituitarism, will initiate hormone replacement therapy for the 6 month duration of the study, (except for post-menopausal females) and will be required to discontinue the replacement at the end of 6 months, to re-evaluate hypopituitarism.
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E.4 | Principal exclusion criteria |
• Patients who have had prior surgery, radiotherapy, somatostatin analog or dopamine agonist therapy for their NFT. • Visual field abnormalities, which will be referred for surgery. • Evidence of a secretory pituitary tumor as evidenced by elevated IGF-1, increased 24 hr urinary free cortisol level, or prolactin >200 ng/ml. • It is anticipated that the patient may require pituitary surgery or radiotherapy during the study period. • Clinically significant renal or hepatic abnormalities. • Active malignant pathology. • Evidence of drug/alcohol abuse. • The patient has received any unlicensed drug within 30 days prior to screening. • Pregnancy (as indicated by serum ß-HCG pregnancy test, for all female patients with the potential to become pregnant) and patients who are breastfeeding.
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E.5 End points |
E.5.1 | Primary end point(s) |
Tumor size: measured by MRI at 0 and 6 months, and 1 month after treatment is discontinued. Macroadenoma is defined as a tumor > 10 mm diameter on MRI. Tumor extension will be recorded as intrasellular, suprasellar or “other extension’ if there is evidence of spread beyond the immediate sellar region eg into the adjacent cavernous sinus (Gittoes, Clin Endo, 1994). In defining response criteria of tumor shrinkage there is no published data on tumor volume response of NFT to medical therapy. The following volume responses will be used based on volume responses observed in GH secreting adenomas in acromegalic patients on medical therapy. A 25% decrease in volume will be regarded as clinically relevant based on analysis of GH secreting tumor responses to octreotide in the following published studies: Primary Medical Therapy and Significant Tumor Size Reduction (>25%) Octreotide SC (Lundin) 11/17 Octreotide SC (Newman) 3/13 Octreotide LAR Depot (Colao) 10/15 Lanreotide (Baldelli) 5/23 Lanreotide (Cozzi) 5/5 Octreotide LAR Depot (Beven) 18/24
Success of the study will be determined depending on the number of patients responding to treatment. Number of patients responding will be classified as: small if >/= 30% patients experience a 25% reduction, moderate if 30-60% of patients experience a 25% reduction, and large if > 60% reduce their tumor volume by 25%.
We will also classify tumor responses on a scale of 1-5 as follows: should be included in secondary endpoints = analysis patient based 5: maximum response: complete tumor resolution 4: 75-100% tumor shrinkage 3: 50-75% tumor shrinkage 2: 25-50% tumor shrinkage 1: 0-25% tumor shrinkage 0: no response -1: tumor expansion |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Information not present in EudraCT |
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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LPLV after month 6 or Follow-Up Period: After the 6 months period patients showing a reduction in tumor size will have the possibility to enter a follow-up treatment period until drug approval or discontinuation by Novartis.
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |