E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage III (Unresectable) or Stage IV Melanoma. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025670 |
E.1.2 | Term | Malignant melanoma stage III |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025671 |
E.1.2 | Term | Malignant melanoma stage IV |
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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 6-month Progression Free Survival (PFS). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the following: • Objective Response Rate (ORR). • 1-year Survival. • Overall Survival (OS). • Duration of Response (DOR). • Clinical Benefit Rate (CBR). • Time to Response (TTR). • Safety and tolerability of YM155 given in combination with docetaxel. |
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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 |
The pharmacogenomic sub-study is included in the main protocol.
The objective of this research is to comprehensively analyze: • Suspected disease-related genes such as oncogenes, survivin and vascular endothelial growth factor (VEGF) • Genes potentially involved in drug excretion and/or metabolism such as the organic anion/cation transporters (OAT, OCT) • Genes of relevance to toxicity/safety issues, to be identified in a precautionary / retrospective setting |
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E.3 | Principal inclusion criteria |
A subject is eligible for the study if all of the following apply: 1. Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved written Informed Consent and privacy language as per national regulations (e.g., HIPAA Authorization for U.S. sites) must be obtained from the subject or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
2. Male or female subjects aged 18 years or older at the Baseline Visit.
3. Histologically or cytologically confirmed Stage III (unresectable) or Stage IV melanoma.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at the Baseline Visit.
5. No prior systemic treatment for advanced melanoma (Stage III or Stage IV). Treatment with a kinase inhibitor, biologic therapy, vaccine or investigational treatment for unknown primary melanoma is allowed if administered in the adjuvant setting > 4 weeks prior to the Baseline Visit. Treatment with an immunotherapy is allowed if administered > 6 weeks prior to the Baseline Visit.
6. Completion of palliative radiation treatment if administered > 4 weeks prior to the Baseline Visit.
7. At least one measurable target lesion according to RECIST (Version 1.1). o If the lesion received prior radiation, there must be evidence of disease progression since last radiated.
8. Subjects with a previous history of non-melanoma malignancy are eligible for this study only if the subject meets the following criteria for a cancer survivor: o The subject has undergone potentially curative therapy for all prior malignancies including basal cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix. o The subject has been considered disease free for at least 5 years.
9. Life expectancy > 12 weeks at the Baseline Visit.
10. If the subject is female, she must be non-pregnant and non-lactating. Each site will administer a pregnancy test to any female of childbearing potential during the Screening Period and at the Baseline Visit. Only females with negative pregnancy test results will be eligible. All sexually active males and females of childbearing potential must agree to use an adequate method of contraception throughout the study period. |
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E.4 | Principal exclusion criteria |
A subject will be excluded from participation if any of the following apply: 1. Major surgery within 21 days of the Baseline Visit.
2. Presence of brain metastases.
3. Previously treated with YM155.
4. Primary ocular, choroidal or mucosal melanoma.
5. Neuropathy > Grade 2 at Baseline Visit.
6. Inadequate marrow, hepatic and/or renal function at the Baseline Visit defined as: o Serum creatinine > 1.5 x upper limit of normal (ULN) or calculated serum creatinine clearance < 60 mL/min. o ANC < 1500/mm3. o Platelet < 100,000/mm3. o Alanine transaminase (ALT) and Aspartate transaminase (AST) > 1.5 x ULN concomitant with alkaline phosphatase > 2.5 x ULN. o Bilirubin > ULN.
7. The subject has significant and/or uncontrolled cardiac, renal, hepatic or other systemic disorders, deep tissue infections or significant psychological conditions at Baseline Visit that in the Investigator’s judgment would jeopardize subject enrollment or compliance with the study procedures.
8. Hypersensitivity to docetaxel or polysorbate 80.
9. Known history of positive test for Hepatitis B surface Antigen (HsbAg) or hepatitis C antibody or history of positive test for Human Immunodeficiency Virus (HIV). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for the study is progression free survival (PFS). The 6-month PFS is defined as the probability that a patient survives without objective tumor progression at 6 months (24 weeks) following the first dose of study regimen. Objective tumor progression is assessed by the independent radiological review. |
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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 | Yes |
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 | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Potential efficacy biomarkers |
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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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
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
| 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 | No |
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
|
End of study reflects when the last subject receives the last survival contact. The End of Study date could include a study visit, successful telephone contact, etc. Definition provided in the protocol. |
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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 | 3 |
E.8.9.1 | In the Member State concerned days | |
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 | 3 |