E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Previously Treated 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 | 10060862 |
E.1.2 | Term | Prostate cancer |
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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 |
Phase 1b (Open label): • To identify safe dose levels of AMG 102, up to 15 mg/kg Q3W, to combine with mitoxantrone and prednisone (MP) Phase 2 (Double-blind): • To estimate with adequate precision the effect of the addition of AMG 102 to MP, compared with placebo plus MP, as assessed by the hazard ratio (HR) for overall survival (OS) of previously treated subjects with castrate-resistant prostate cancer (CRPC) |
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E.2.2 | Secondary objectives of the trial |
Phase 1b • To evaluate the incidence of adverse events, abnormal laboratory values not defined as dose limiting toxicities (DLTs), and anti-AMG 102 antibody formation. • To evaluate the pharmacokinetics (PK) of AMG 102 (Cmax and Cmin). Phase 2 • To evaluate the effect of the addition of AMG 102 to MP on progression-free survival (PFS), percentage changes in prostate-specific antigen (PSA) level, PSA response rates, RECIST response rates, patient reported outcomes including pain, incidence of adverse events, laboratory abnormalities, and anti-AMG 102 antibody formation. • To evaluate the PK (Cmax and Cmin) of AMG 102, and assess the impact of co-administration of AMG 102 on the PK of mitoxantrone in a sub-group of subjects at selected sites. |
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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 |
Phase 2, PK sub-study Approximately 36 subjects (about 12 subjects per arm) of Phase 2 will be enrolled to a PK sub-study to evaluate the impact of co-administration of AMG 102 on the PK of chemotherapy. |
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E.3 | Principal inclusion criteria |
Disease-related • Pathologically confirmed adenocarcinoma of the prostate • Radiographic evidence of metastatic disease • Progressive disease meeting at least one of the following criteria: 1) a sequence of at least 2 rising PSA values measured at a minimum of 1 week apart with a 2 ng/mL minimum starting value, or 2) progression according to RECIST criteria for measurable lesions, or 3) appearance of 2 or more new lesions on bone scan. • History of prior taxane-based chemotherapy for metastatic prostate cancer; no more than one prior chemotherapy regimen for CRPC is allowed (estramustine will be considered as chemotherapy) • ECOG Performance status 0 or 1 • Life expectancy ≥ 3 months Demographic Men ≥ 18 years of age Laboratory • Castrate levels of serum testosterone (< 50 ng/dL) • PSA ≥ 2 ng/mL • Hemoglobin ≥ 9 g/dL (can be post-transfusion) • Absolute neutrophil count ≥ 1.5 x 109/L • Platelet count ≥ 100 x 109/L (without transfusion within 14 days before enrollment or randomization) • Creatinine ≤ 2X ULN • Aspartate aminotransferase (AST) and alanine amino transferase (ALT) ≤ 3.0 x ULN • Total bilirubin ≤ 1.5x ULN • Partial thromboplastin time (PTT) ≤ 1.5 x ULN and international normalized ratio (INR) ≤ ULN. Medications For patients without a history of surgical castration, continued GnRH analog administration is required |
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E.4 | Principal exclusion criteria |
Disease-related • Treatment with external beam radiotherapy ≤ 14 days before enrollment or radiopharmaceutical ≤8 weeks • ≤ 4 weeks since receipt of most recent prior chemotherapy, non-GnRH analog hormonal therapy (except for continuing corticosteroids) or other systemic therapy to treat prostate cancer and <6 weeks since receipt of prior bevacizumab. Patients with evidence of an antiandrogen withdrawal response must demonstrate objective or PSA progression following the response. • Known CNS metastases (epidural disease is allowed if it has been treated and there is no progression in the treated area). Cardiac • Significant cardiovascular disease (CHF class III or IV, uncontrolled angina, MI within 6 months of enrollment); patients with medically stable atrial fibrillation may be included. • LVEF < 50% by MUGA or ECHO Medications • Treatment of infection with systemic anti-infectives within 7 days before enrollment (with the exception of uncomplicated urinary tract infection) • Concurrent or prior (within 7 days of enrollment) anticoagulation therapy, except that use of low dose coumarin-type anticoagulants or heparins for prophylaxis against central venous catheter thrombosis is allowed General • Major surgical procedure ≤ 30 days before enrollment or not yet recovered from prior major surgery • Minor surgery ≤14 days before enrollment or not yet recovered from prior minor surgery; central venous catheter placement is allowed at any time prior to enrollment provided that patient has recovered and any surgical wound has healed • Any prior or synchronous malignancy (except for non-melanomatous skin cancer or lentigo maligna) other than the study disease, unless treated with curative intent with no evidence of disease ≤ 3 years before enrollment • Presence of peripheral neuropathy > Grade 1 • Presence of peripheral edema > Grade 2 • Known proteinuria > 1 gram/day (subjects with >2+ protein on screening urinalysis require a quantitative evaluation of urine protein) • Any clinically significant medical condition other than cancer, including cardiovascular disease or COPD, which in the opinion of the investigator would interfere with the safe delivery of study treatment or increase risk of toxicity • History of any medical condition that in the opinion of the investigator, may increase the risks associated with study participation or study treatments or may interfere with the conduct of the study or interpretation of study results • Known positive test for HIV, hepatitis C, chronic or active hepatitis B • Serious or non-healing wound • Unable to begin protocol specified treatment within 7 days after enrollment • Other investigational procedures are excluded. • Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s), or subject is receiving other investigational agent(s). • Treated previously with c-Met or HGF targeted therapy • Subject is not using adequate contraceptive precautions. • Subject has known sensitivity to any of the products to be administered during dosing. • Subject will not be available for follow-up assessment. • Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase 1: To identify a safe dose level of AMG 102, up to 15 mg/kg Q3W, to combine with mitoxantrone and prednisone (MP)
Phase 2: To estimate with adequate precision the effect of the addition of AMG 102 to MP, compared with placebo plus MP, as assessed by the hazard ratio (HR) for overall survival (OS) of previously treated subjects with castrate-resistant prostate cancer (CRPC) |
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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 | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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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 | 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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Phase 1b (Completed) is open label, Phase 2 is double blind placebo controlled |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
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 | 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 | 4 |
E.8.9.1 | In the Member State concerned months | 8 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |