E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects suffering from advanced, metastatic soft tissue sarcoma. |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10015838 |
E.1.2 | Term | Extraskeletal chondrosarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061527 |
E.1.2 | Term | Neurofibrosarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025566 |
E.1.2 | Term | Malignant haemangiopericytoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008733 |
E.1.2 | Term | Chondromyxoid fibroma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10045515 |
E.1.2 | Term | Undifferentiated sarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10024627 |
E.1.2 | Term | Liposarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016637 |
E.1.2 | Term | Fibrosarcoma NOS |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025552 |
E.1.2 | Term | Malignant fibrous histiocytoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039022 |
E.1.2 | Term | Rhabdomyosarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10024189 |
E.1.2 | Term | Leiomyosarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10002476 |
E.1.2 | Term | Angiosarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10042863 |
E.1.2 | Term | Synovial sarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
Investigation of progression-free survival on the basis of RECIST criteria |
|
E.2.2 | Secondary objectives of the trial |
Investigation on: Overall survival up to 1 year after beginning of the treatment Total dose required per patient and dosing schedule Pharmacokinetics and pharmacodynamics Safety and tolerability (adverse events, pathological findings in EKG and cardiological investigation in a subpopulation included at the centre in Heidelberg) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with verified, metastatic soft tissue sarcoma of following histologies: a. Undifferentiated highgrade pleomorphic sarcoma/pleomorphic malignant fibrous histiocytoma, b. Undifferentiated pleomorphic sarcoma with grand cells/ grand cells fibrotic histiocytoma, c. Undifferentiated pleomorphic sarcoma with prominent inflammation/ inflammated MFH, d. Myxofibrosarcoma, e. Liposarcoma, f. Synovial sarcoma, g. Rhabdomyosarcoma (pleomorphic, alveolar und embryonal), h. Leiomyosarcoma, i. Adult fibrosarcoma, j. Angiosarcoma, k. Malignant haemangiopericytoma/ malignant solitaire fibrous tumor, l. Malignant peripheral neurilemma tumor, m. Extraskeletal mesenchymal chondrosarcoma, n. Extraskeletal myxoid chondrosarcoma, o. Undifferentiated sarcoma of NOS (not otherwise specified) type. 2. Verified relapse or disease progression at the study inclusion, i.e. therapeutic failure of the first line therapy with antracyclines, 3. Measurable disease according to RECIST criteria, 4. Previous systemic therapy of advanced and/or metastatic disease, 5. An interval of at least 4 weeks to the last surgery, chemotherapy or radiation, 6. Age over 18, 7. Following laboratory findings: a. ANC ≥ 1.0 x 10³/mm³, b.Platelets ≥ 100.000/mm³, c. haemoglobin ≥ 9 g/dl, d. creatinine < 1.5 x ULN (upper limit of normal), e. AST und/oder ALT < 2.5 x ULN, f. total bilirubin < 1.5 x ULN, 8. Life expectancy of at least 12 weeks, 9. Negative pregnancy test, 10. Consent to an effective contraception during and up to 6 month after the study completion, 11. Written informed consent, 12. Ability to understand the goal and consequences of this clinical trial. |
|
E.4 | Principal exclusion criteria |
1. Proof of the following histologies: a. gastrointestinal stromal tumor (GIST), b. malignant mesothelioma, c. neuroblastoma, d. osteosarcoma, e. Ewing's sarcoma/PNET, 2. Concurrent radio- or chemotherapy, 3. Participation in another interventional trial within 4 weeks prior to the inclusion, 4. Previous therapy with another HDAC-inhibitor (e.g. depsipeptide, MS-275, LAQ-824, PXD-101 und valproic acid). Patients, who underwent a therapy with valproic acid for treatment of seizures, can be included after a wash-out period of at least 30 days, 5. Symptomatic brain metastases, that have not been treated by radiotherapy. The interval between the last radiation and the study inclusion must not be shorter than 30 days, 6. Previous malignant disease (except for a non-melanoma of the skin and a carcinoma in situ of uterus), unless in complete remission and after the last therapy for at least 5 years, 7. Ejection fraction < 40 %, 8. Nursing, 9. Known allergy against the IMP or drugs with similar chemical structure or additives, 10. Active hepatitis B and/or C and HIV-infection
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E.5 End points |
E.5.1 | Primary end point(s) |
|
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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | 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 | 4 |
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 | 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 | 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
|
See protocol (section 7.8) |
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |