E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Male adults with Hormone Refractory Prostate Cancer who have progressed, as evidenced by PSA progression or progression of measurable disease, after at least 1 prior chemotherapy regimen. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.0 |
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 |
To evaluate the efficacy of YM155 based on the percentage of subjects that obtain a PSA response. PSA response is defined as a ≥ 50% reduction in PSA that is confirmed by a second PSA value 3 weeks apart. The reference PSA value for these decreases is the baseline PSA value.
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E.2.2 | Secondary objectives of the trial |
Secondary • To measure the percentage of PSA decrease. • To measure duration of PSA response. • To measure the time to PSA progression. • To evaluate overall survival (OS). • To measure objective tumor response (Complete Response [CR] and Partial Response [PR]) in subjects with measurable disease. • To measure change in pain based upon Memorial Pain Scale. • To evaluate progression free survival (PFS). • To evaluate safety based on clinical laboratory assessments, 12-lead ECGs, vital signs, physical examinations, and adverse events.
Additional Exploratory Objectives: • To assess population pharmacokinetics of YM155. • Alpha-1-acid glycoprotein (AAG) will be obtained on all subjects at baseline and at the Final Visit/Early Termination in order to evaluate the level of AAG in relation to treatment outcomes and survival. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Subjects are eligible for the study if all of the following apply: 1) Written informed consent and HIPAA (U.S. sites only) authorization have been obtained. 2) Male subjects ≥18 years of age with histologically or cytologically confirmed prostate cancer. 3) Subject has a serum testosterone level < 50 ng/dL. 4) Subject has been treated with at least 1 prior chemotherapy regimen. For US subjects, the subject had to have at least 1 regimen containing taxotere and prednisone. 5) PSA at baseline must be at least 5 ng/mL. 6) Subject has evidence of disease progression on hormonal therapy and following at least one course of chemotherapy. Disease progression prior to study entry is defined by any of the following: a. Appearance of at least one new lesion on bone scintigraphy or X-ray as compared to previous evaluations, or b. Appearance of new soft tissue disease or an increase of at least 20% in the sum of the largest diameters of the previously measurable soft tissue disease as documented by appropriate imaging modality, or c. A rising PSA defined as an increase in PSA on 2 consecutive measurements separated by at least 1 week compared to a reference PSA. 7) ECOG performance status 0-2. 8) Life expectancy greater than 12 weeks. 9) Willingness to comply with all procedures and assessments. 10) In the case of medical castration, subject is receiving stable dose of LHRH-agonist or LHRH-antagonist. 11) Subject must be off anti-androgen therapy at least 4 weeks prior to dosing for flutamide and other secondary hormonal therapy and 6 weeks for nilutaminde and bicalutamide. |
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E.4 | Principal exclusion criteria |
Subjects will be excluded from the study if they meet any of the following criteria: 1) Radiation therapy within 4 weeks prior to the start of YM155. 2) Prior strontium or samarium or other radioisotope therapy within 12 weeks prior to start of YM155. 3) Has metastases to the brain. 4) Concurrent anticancer therapy (chemotherapy, vaccines, immunotherapy) delivered within the last 4 weeks (6 weeks for nitrosoureas or mitomycin C, or other agents known to cause prolonged marrow suppression) except for continued use without modification of LHRH-agonists, LHRH-antagonists, and bisphosphonates initiated 4 weeks or more before the start of YM155. 5) History of other malignancy in the last 5 years. 6) Participated in a clinical study involving an investigational drug or device within 4 weeks prior to the start of YM155. 7) Known history of positive test for hepatitis B surface antigen (HbsAg) or hepatitis C antibody or history of positive test for human immunodeficiency virus (HIV) infection. 8) Had major surgery within the past 21 days prior to the start of YM155. 9) Uncontrolled intercurrent illness, including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, seizure disorder, or psychiatric illness/social situations that would limit compliance with study requirements. 10) Subjects with a urine protein of 2+ (grade 2) and above prior to start of YM155. 11) Has inadequate bone marrow, renal, and hepatic function as evidenced by: a. Absolute neutrophil count (ANC) ≤ 1500/mm3 and platelet count ≤ 100,000/mm3, b. Serum creatinine ≥ 1.5 upper limit of normal (ULN) or calculated creatinine clearance < 60 mL/min at screening, c. Total bilirubin ≥ 1.5 times the upper limit of normal (ULN) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 1, d. Alanine transaminase (ALT) and aspartate transaminase (AST) ≥ 2.5 X ULN (NCI CTCAE Grade 1); if the subject has documented liver metastases and/or hepatoma, ALT and AST ≥ 5 X ULN. 12) Any clinical condition, which, in the opinion of the investigator, would not allow safe conduct of the study. 13) Use of any alternative medications (e.g. herbal supplements) within 2 weeks prior to the start of study drug. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• The rate of PSA response. PSA response is defined as a ≥ 50% reduction in PSA without evidence of clinical or radiographic disease progression that is confirmed by a second PSA value 3 weeks apart. The reference PSA value for these decreases is the baseline PSA value. |
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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 | Information not present in EudraCT |
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) | 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 | 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 | 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.8.5 | 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 | 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 | 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
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |