| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic Castrate-Resistant Prostate Cancer |
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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 | 10036909 |
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| 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 | 10062904 |
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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 |
| The primary objective of this study is to confirm the effect of tasquinimod on delaying disease progression or death compared with placebo. |
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| E.2.2 | Secondary objectives of the trial |
| To determine the effect of tasquinimod on overall survival (OS), time to symptomatic progression, additional radiological and clinical efficacy endpoints, quality of life (QoL) parameters, and safety as compared with placebo. • To assess the pharmacokinetics of tasquinimod in men with metastatic CRPC. |
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| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
FARMACOGENETICA: Versione:1.0 Data:2010/10/22 Titolo:Studio di Fase 3, Randomizzato, in Doppio Cieco, Controllato con Placebo, di Tasquinimod in Uomini con Carcinoma Metastatico della Prostata Resistente alla Castrazione Obiettivi:I campioni di sangue e di siero identificati da un codice singolo potrebbero essere conservati per possibili analisi future oltre la fine dello studio. I campioni della biobanca di DNA/RNA per le valutazioni di farmacogenomica verranno raccolti solo per i pazienti che abbiano acconsentito firmando un modulo di consenso informato separato per la farmacogenetica e la farmacogenomica. Ulteriori analisi di biomarcatori, farmacogenetica e farmacogenomica sui campioni della biobanca verranno effettuati al di fuori dello scopo dello studio principale e verranno riportati separatamente. Le analisi potrebbero includere: biomarcatori esplorativi per saggi di marcatori di meccanismo (ad esempio recettori solubili per prodotti terminali della glicazione [RAGE], TSP-1, S100A9, e proteine angiochine o peptidi) e per lo screening del profilo di citochine per l`analisi di geni di rilevanza per la patologia del carcinoma prostatico con lo scopo di correlare la variazione nella sequanza del DNA del singolo paziente con la sicurezza, tollerabilita`, farmacocinetica e potenziali benefici clinici.
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| E.3 | Principal inclusion criteria |
| 1. Age at least 18 years at the time of signing the informed consent form. For patients in Taiwan the minimum age is 20 years. 2. Histologically confirmed diagnosis of adenocarcinoma of the prostate. 3. Evidence of bone metastatic disease on radiographic examination, whether from bone scan (bone lesions) or other imaging modality. 4. Castrate levels of serum testosterone (≤50 ng/dL or 1.7 nmol/L). 5. Evidence of progressive disease after castration levels of testosterone have been achieved, defined by any of the following criteria: • Increasing serum PSA levels, the most recent value ≥2 ng/mL. (Increasing levels must be confirmed by 3 consecutive PSA measurements, within 15 months [Preferably with 14 days, but with at least 7 days between each measurement].) • Progression of soft tissue metastasis documented within 6 weeks of enrollment (computed tomography [CT] scan or magnetic resonance imaging [MRI]) • Progression of bone disease (at least 1 new bone lesion as measured by bone scan within the past 12 weeks) 6. Karnofsky score ≥70%. 7. Laboratory values as follows: • Hemoglobin ≥100 g/L (>10 g/dL) • Absolute neutrophil count ≥1500/μL • Platelets ≥100 000/μL • Serum creatinine ≤1.5 times the upper limit of normal (ULN) • Total bilirubin ≤1.5 times ULN • Aspartate aminotransferase and alanine aminotransferase ≤3 times ULN 8. If sexually active with partner of childbearing potential, patient will agree to use adequate contraceptive methods (barrier contraceptive with spermicide or vasectomy) while on study drug. The adequate contraceptive method should be continued for 14 days after the patient stops taking study drug. 9. No evidence (within 5 years) of prior malignancies (except successfully treated basal cell or squamous cell carcinoma of the skin). 10. Able to swallow and retain oral medication. 11. Able to adhere to the study visit schedule and other protocol requirements. 12. Ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to cooperate with the investigator and to comply with the requirements of the entire study. 13. Able (or patient’s legal guardian, if applicable) to sign and date the written informed consent after being informed of the full nature and purpose of the study, including possible risks and side effects, and given ample time and opportunity to read and understand this information. |
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| E.4 | Principal exclusion criteria |
| 1. Prior cytotoxic chemotherapy for the treatment of prostate cancer within 2 years. 2. Previous anticancer therapy using radiation, biologics or vaccines, including sipuleucel-T (Provenge), abiraterone or MDV3100 within 4 weeks prior to the start of study treatment. If radiation therapy is applied after baseline scan, a new baseline scan needs to be done at least 4 weeks after the radiation therapy. 3. Previous therapy with antiandrogens within 4 weeks (within 6 weeks for bicalutamide eg, Casodex) 4. Concurrent use of other anticancer agents or treatments, with the following exceptions: • Ongoing treatment with luteinizing hormone-releasing hormone (LHRH) agonists or antagonists, denosumab (Prolia) or bisphosphonate (eg, zoledronic acid) is allowed. Ongoing treatment should be kept at a stable schedule; however, if medically required, a change of dose, compound, or both is allowed. 5. Any treatment modalities involving major surgery within 4 weeks prior to the start of study treatment. 6. Prostate cancer pain that requires ongoing treatment with narcotic analgesics or warrants the initiation of radio- or chemotherapy. 7. Ongoing treatment with warfarin. Treatment with other anticoagulants is allowed but should be discussed with medical monitor before inclusion. 8. Maintenance treatment with corticosteroids corresponding to a prednisolone or prednisone dose above 10 mg/day. The dose must have been stable for at least 5 days. 9. Systemic exposure to ketoconazole or other strong cytochrome P450 (CYP) 3A4 isozyme inhibitors or inducers within 14 days prior to the start of study treatment. Systemic exposure to amiodarone is not allowed within 1 year prior to the start of study treatment. 10. Ongoing treatment with sensitive CYP1A2 substrate or CYP1A2 substrate with narrow therapeutic range at the start of study treatment. 11. Ongoing treatment with CYP3A4 substrate with narrow therapeutic range at the start of study treatment. 12. Simultaneous participation in any other study involving treatment with investigational drugs or having received treatment with investigational drugs less than 4 weeks prior to the start of study treatment. 13. Myocardial infarction, percutaneous coronary intervention, acute coronary syndrome, coronary artery bypass graft, class III/IV congestive heart failure, cerebrovascular accident, transient ischemic attack, or limb claudication at rest, within 6 months prior to start of study treatment and ongoing symptomatic dysrhythmias, unstable angina, uncontrolled hypertension, and uncontrolled atrial or ventricular arrhythmias. 14. History of pancreatitis. 15. Known brain or epidural metastases. 16. Known positive serology for HIV (patients with known history of HIV will be excluded because of potential for unforeseen toxicity and morbidity in an immunocompromised host). 17. Chronic hepatitis with advanced, decompensated hepatic disease or cirrhosis of the liver or history of a chronic viral hepatitis or known viral hepatitis carrier (patients who have recovered from hepatitis will be allowed to enter the study). 18. Patients with active tuberculosis (TB), or with known, untreated latent TB. (Country-specific TB therapy should have been given for at least 30 days prior to the start of study treatment and the patient should intend to complete the entire course of that therapy). Refer to protocol for a complete list. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is progression-free survival (PFS) defined as the time from the date of randomization to the date of radiological progression or death. Radiological progression is defined by any of the following criteria: • Progression of soft tissue lesions according to the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) • Progression of bone lesions detected with bone scan according to Prostate Cancer Working Group 2 (PCWG2) criteria • Radiologically confirmed spinal cord compression or pathological fracture due to malignant 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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 | Yes |
| 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 | 11 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 145 |
| 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 | 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
|
| Non applicabile (LPLV corrisponde alla fine dello studio). |
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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 | 4 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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