E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Unresectable or metastatic soft-tissue sarcoma |
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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 | 10039491 |
E.1.2 | Term | Sarcoma |
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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 |
The primary objective is to assess the difference in progression-free survival (PFS) between subjects treated with palifosfamide tris plus doxorubicin versus doxorubicin alone. |
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E.2.2 | Secondary objectives of the trial |
The secondary efficacy objectives are to assess the following variables between subjects treated with palifosfamide tris plus doxorubicin versus doxorubicin alone: safety and tolerability, time to progression (TTP), overall response rate ([ORR] proportion of subjects with confirmed partial and complete responses) per RECIST (response evaluation criteria in solid tumors) guidelines (see Appendix 2, overall response duration and time to objective response |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age &#8805;18 years 2. Histological or cytological documentation of sarcoma (excluding alveolar soft-part sarcoma, chondrosarcoma, dermatofibrosarcoma, Ewing sarcoma, GIST, Kaposi sarcoma, mixed mesodermal tumor, osteosarcoma, radiation induced sarcomas, and unresectable low grade liposarcoma) who have failed &#8804;2 prior regimens including adjuvant therapy, or &#8804;1 prior regimen for metastatic/unresectable disease, and for whom treatment with doxorubicin is considered medically acceptable. Prior treatment with IFOS is acceptable. 3. Have measurable disease as per RECIST criteria (Appendix 2) 4. ECOG Performance Status of 0 or 1 (Appendix 3) 5. Anthracyclin naïve 6. Life expectancy of &#8805;12 weeks 7. Adequate bone marrow, liver, and renal function, as assessed by the following laboratory requirements conducted within 14 days prior to dosing: a. Hemoglobin &#8805;9.0 g/dL b. Absolute neutrophil count (ANC) &#8805;1,500/mm3 c. Platelet count &#8805;100,000/mm3 d. Total bilirubin &#8804;1.5×ULN (upper limit of normal) e. ALT and AST &#8804;2.5×ULN or 5×ULN with hepatic disease f. Partial thromboplastin [PT]-INR/activated partial thromboplastin time [PTT] <1.5×ULN (&#8804;2.0×ULN for subjects on anticoagulation prophylactic regimen). Subjects who are being therapeutically anticoagulated with an agent such as Coumadin (warfarin sodium) or heparin are allowed provided there is no prior evidence of underlying abnormality in coagulation parameters. If an interaction between study drug and anticoagulant is suspected, anticoagulation monitoring should be increased as appropriate. g. Serum creatinine &#8804;ULN 8. Written informed consent must be obtained from a potential subject prior to the conduct of any study-specific procedures 9. Male and female subjects must agree to use adequate birth control measures/barrier control during the course of the trial 10. Women of childbearing potential must have a urine pregnancy test performed within 14 days of the start of treatment |
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E.4 | Principal exclusion criteria |
1. Has any one of the following sarcoma sub types: alveolar soft-part sarcoma, chondrosarcoma, dermatofibrosarcoma, Ewing sarcoma, GIST, Kaposi sarcoma, mixed mesodermal tumor, osteosarcoma, radiation induced sarcomas, and unresectable low grade liposarcoma. 2. Clinically evident congestive heart failure >Class II of the New York Heart Association (NYHA) guidelines (Appendix 4) 3. Serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia, or ventricular arrhythmias classified as Lown III, IV, or V (Appendix 4) 4. History and/or signs of active coronary artery disease/ischemia with or without angina pectoris 5. Serious myocardial dysfunction defined as scintigraphically (MUGA [multiple gated acquisition scan], myocardial scintigram) or ultrasound-determined absolute left ventricular ejection fraction (LVEF) <45% 6. History of HIV infection 7. Prior nephrectomy or history of urinary tract obstruction 8. Active, clinically serious infection requiring systemic antibacterial, antifungal, or antiviral therapy 9. Any major surgery within 3 weeks prior to start of treatment 10. Metastatic brain or meningeal tumors, unless the subject is >6 months from definitive therapy and has a negative imaging study within 4 weeks of study entry. In addition, the subject must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable, provided the dose is stable for 1 month prior to study start, and following screening radiographic studies). 11. Previous malignancy (except cervical carcinoma in situ, adequately treated basal cell carcinoma, or superficial bladder tumors [Ta, Tis, & T1] or other malignancies curatively treated >5 years prior to entry) 12. Pregnancy or lactation 13. Substance abuse or medical, psychological, or social conditions that may interfere with the subjects participation in the study or evaluation of the study results |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable (PFS) is defined as time from Day 1 (first dose of study drug) to the date of documented, objective PD, radiological or clinical findings (defined as an increase ECOG PS of >=3) whichever is earlier, or death (if prior to progresion) Subjects without PD or death occuring as of the time of analysis will be censored as of the lst date of disease evaluation, but all subjects will be followed for survival. |
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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 | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | 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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
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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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |