E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with prostate cancer presenting Neuro-Endocrine (NE) differentiation developing non metatstatic castrate resistant disease and eligible to second line hormone treatment with non steroidal anti androgens. |
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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 | SOC |
E.1.2 | Classification code | 10029104 |
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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 |
To assess the efficacy in terms of Progression-free survival (PFS) of the administration of non steroidal anti androgens and LHRH-a (Arm A) versus lanreotide in addition to non steroidal anti androgens and LHRH-a (Arm B) as second line approach in non metastatic prostate cancer patients with castrate resistant disease and elevated CgA circulating levels. According to the updated guidelines of the PCWG2 Progression-free survival (PFS) will be considered a composite end point defined as the time from random assignment to disease progression in bone or soft-tissue, symptoms, or death.A rising PSA alone will not be considered an indicator of disease progression since radiographic or symptomatic progression better reflect changes in clinical status.Subjects stopping the study for any reason, including isolated PSA increase, will be censored at their last date of evaluation.Patients without tumor progression or death at the time of analysis will be censored at their last date of evaluation |
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E.2.2 | Secondary objectives of the trial |
To compare safety between Arm A and Arm B. To compare PSA response and median times to PSA response between Arm A and Arm B. To compare PSA doubling median times between Arm A and Arm B. To compare median times to PSA progression and Overall Survival (OS defined as the time from randomisation to death due to any cause). To compare the reduction from baseline in CgA serum levels between Arm A and Arm B. To correlate the changes in serum CgA with PSA response. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age equal to or greater than 18. Histologically proven diagnosis of prostate cancer. Evidence of PSA progression despite castrate levels of testosterone (<50 ng/dL) following orchiectomy or during therapy with luteininzing hormone releasing hormone agonists (LHRH-a). Chromogranin A elevation above normal range (cut off levels will be > 20 U/L for ELISA assay and > 100 ng/ml for IRMA assay). ECOG Performance Status 0-1 Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 14 days prior to the start of the study treatment: Hb > 9.0 g/dl, absolute neutrophil count (ANC) > 1.500/mm3, platelet count >100.000/ml, total bilirubin < 1.5 times the upper limit of normal (ULN), AST and ALT < 2.5 x ULN (< 5 x ULN for patients with liver involvement of their cancer), serum creatinine < 1 x ULN Life expectancy of at least 6 months. Written informed consent |
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E.4 | Principal exclusion criteria |
Patients with radiological signs of metastatic disease. Patients who according to the investigator opinion are candidate to be treated immediately with chemotherapy (e.g. docetaxel). Patients previously treated with total androgen ablation. Patients eligible to steroidal anti androgens. Diastolic blood pressure >100 mm/Hg despite anti-hypertensive drugs. Clinically significant cardiovascular disease (e.g. cerebrovascular accidents, myocardial infarction, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication). Renal impairment (creatinine levels above NL).Severe Parkinson disease. Known history of atrophic gastritis. Known history of cholelithiasis. Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma effectively treated. Previous or concomitant treatment with a somatostatin analogue. Patients with known allergy to any of the components of the study medication.Concomitant assumption of drugs able to interfere with CgA synthesis. Treatment with any investigational drug within 30 days prior to enrolment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To assess the efficacy in terms of PFS of the administration of non steroidal anti androgens and LHRH-a (Arm A) versus lanreotide in addition to non steroidal anti androgens and LHRH-a (Arm B) as second line approach in prostate cancer patient with castrate resistant disease and elevated CgA circulating levels. As per PCWG2 updated guidelines PFS will be considered a composite end point defined as the time from random assignment to disease progression in bone or soft-tissue, symptoms, or death (if death occurs before progression). |
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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) | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
nessun trattamento sperimentale aggiuntivo |
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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 | 25 |
E.8.5 | The trial involves multiple Member States | No |
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 | Yes |
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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Incidenza/gravita` degli eventi avversi tali da rappresentare un pericolo potenziale per la salute dei soggetti in studio.Arruolamento insufficiente.Disponibilita` di nuove informazioni che cambiano il rapporto rischio/beneficio atteso |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |