E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced and/or metastatic Soft Tissue Sarcoma |
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MedDRA Classification |
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 |
The principal objective of the trial is to evaluate the therapeutic activity, safety and tolerability of GW786034 in patients with advanced and/or metastatic soft tissue sarcoma who have relapsed following standard therapies or for whom no standard therapy exists. |
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E.2.2 | Secondary objectives of the trial |
A secondary objective is to characterize the population pharmacokinetic parameters of GW786034 in patients with advanced or metastatic soft tissue sarcoma.
A third objective is to investigate whether biomarkers of angiogenesis can predict response to therapy, and understand unexplained / unexpected variations in the safety, response and pharmacodynamic parameters that may be attributable to genetic variations. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
- Histologically or cytologically confirmed high or intermediate grade malignant soft tissue sarcoma; most malignant tumors of non organ origin, as well as skin and uterine leiomyosarcoma are included - Measurable disease (according to RECIST). - Relapsed of refractory disease incurable by surgery or radiotherapy - No more than one combination or two single agents chemotherapy regimen for advanced disease; (neo)adjuvant therapy is not counted towards this requirement - No history of leptomeningeal or brain metastases - At least 21 years of age - WHO performance status 0 or 1 - Adequate bone marrow function (ANC>1.5 10**9/l, PLA>100 10**9/l - Adequate hepatic function (bilirubin within normal range, SGOP/AST and SGPT/ALT <= 2.5*UNL) - Adequate renal function (creatinine clearance > 50 ml/min, calculated or measured; urine protein excretion <= 500 mg/24h - PT/INR/PTT within 1.2 UNL - LVEF above the lower limit of normal for the institution, based on ECHO or MUGA; no class II, III or IV heart failure (NYHA classification); a patient who has a history of class II heart failure and is asymptomatic on treatment may be considered eligible; no arterial or venous thrombosis, myocardial infarction, unstable angina, cardiac angioplasty or stenting within the last 3 months - No uncontrolled or poorly controlled hypertension (SBP >= 150 mm Hg, DBP >=90 mm Hg). Initiation or adjustment of BP medications is permitted prior to study entry, provided that patient has 3 consecutive BP readings less than 150 / 90 mm Hg each separated by a minimum of 24 hrs. These readings need to be collected prior to registration in the study. - No therapeutic dose warfarin; low molecular weight heparin and prophylactic low dose warfarin are permitted. - Able to swallow and retain oral medication - Women should not be pregnant (negative serum pregnancy test at entry) or lactating, and agree to use contraceptive methods (oral contraceptives are not allowed) - Before patient registration, written informed consent must be given. |
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E.4 | Principal exclusion criteria |
The following tumor types are ineligible - Malignant glomus tumors - Embryonal rhabdomyosarcoma - Chondrosarcoma - Osteosarcoma - Ewing tumors / PNET - Gastro-intestinal stromal tumors - Malignant solitary fibrous tumors - Dermofibromatosis sarcoma protuberans - Inflammatory myofibroblastic sarcoma - Neuroblastoma - Malignant mesothelioma - Mixed mesodermal tumors of the uterus |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end-point is the progression free survival, assessed 12 weeks after start of treatment. Progression will be defined according to the "RECIST" criteria.
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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 | 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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | 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) | 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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End of study occurs when all of the following criteria have been satisfied: 1. Thirty days after all patients have either stopped protocol treatment, or have been treated for at least 12 weeks and an evaluation of the disease has been subsequently performed 2. The trial is mature for the analysis of the primary endpoint as defined in the protocol 3. The database has been fully cleaned and frozen for this analysis |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 5 |