E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Localized myxoid / round cell liposarcoma previously untreated with chemotherapy or radiation |
|
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 | 10024630 |
E.1.2 | Term | Liposarcoma non-metastatic |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To determine the pathological complete response (pCR) rate with trabectedin in patients with localized myxoid / round cell liposarcoma (MRCL). |
|
E.2.2 | Secondary objectives of the trial |
- Evaluate the objective response rate by RECIST and contrast such response with changes in radiological density and tumor pathology.
- Describe the incidence and severity of adverse events in this patient population.
- Exploratory, hypothesis-generating pharmacogenomic analyses to correlate molecular parameters in patient samples with clinical outcomes (pCR). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patient´s written informed consent before any study-specific procedure
• Adult patients (≥ 18 years)
• Pathological diagnosis of myxoid / round cell liposarcoma (MRCL) and availability of pathology specimens for central review and pharmacogenomic studies
• Clinical evidence of localized, non-metastatic tumor, including locally recurring disease after initial surgery
• Measurable disease (by RECIST)
• No prior chemotherapy or radiation (except for adjuvant post-operative radiotherapy)
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2 (appendix 1)
• Hematologic variables: o Hemoglobin ≥ 9 g/dL o Absolute neutrophil count (ANC) ≥ 1,500/µL, and o Platelet count ≥ 100,000/µL
• Serum creatinine < 1.5 mg/dL or creatinine clearance > 30 mL/min
• Creatinine phosphokinase (CPK) < 2.5 ULN
• Hepatic function variables: o Total bilirubin < ULN o Total alkaline phosphatase < 2.5 ULN, or if > 2.5 ULN consider alkaline phosphatase liver fraction or GGT or 5’ nucleotidase must be < ULN o AST (serum aspartate transaminase [SGOT]) and ALT (serum alanine transaminase [SGPT]) must be <2.5 x ULN
• Albumin > 25 g/L |
|
E.4 | Principal exclusion criteria |
• Known hypersensitivity to any of the components of the trabectedin i.v. formulation or dexamethasone
• Pregnant or lactating women or any patient of childbearing potential who are not employing adequate contraception
• History of another neoplastic disease (except basal cell carcinoma or cervical carcinoma in situ adequately treated) unless in remission for 5 years or longer
• Known distant metastases
• Other serious illnesses such as congestive heart failure or angina pectoris, myocardial infarction within 1 year before enrollment, uncontrolled arterial hypertension or arrhythmias
• Psychiatric disorder that prevents compliance with protocol
• Active viral hepatitis or chronic liver disease
• Active infection
• Any other unstable medical condition |
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E.5 End points |
E.5.1 | Primary end point(s) |
Pathological Complete Response (pCR) rate |
|
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 | 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) | 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) | Information not present in EudraCT |
E.8.2.2 | Placebo | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 |
|
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
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 | 2 |