E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic and/or unresectable soft tissue or bone sarcoma (excluding GIST). |
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MedDRA Classification |
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 |
Assess the efficacy of AP23573 in patients with advanced sarcoma when administered once daily for 5 consecutive days every two weeks (QDx5). |
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E.2.2 | Secondary objectives of the trial |
Assess safety and tolerability of this study drug regimen.
Evaluate secondary efficacy endpoints, such as time to tumor progression, progression-free survival and duration of response.
Examine AP23573 blood levels and experimental parameters that may predict or indicate response to mTOR inhibition, such as effects on plasma VEGF levels and markers or tumoral PI3K/mTOR-pathway activity. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Patients ≥15 years of age with metastatic and/or unresectable sarcomas of the following histological subgroups: · Bone sarcomas, such as osteosarcoma and Ewings sarcoma · Leiomyosarcoma · Liposarcomas* · Any other soft tissue sarcoma* except GIST * Patients with well-differentiated liposarcoma or desmoid tumors must have demonstrated progressive disease within the previous 6 months. 2. Presence of at least one measurable lesion that: · Can be accurately measured in at least one dimension with longest diameter ≥20 mm using conventional techniques or ≥10 mm with spiral CT scan (or otherwise at least twice the reconstruction interval for CT or MRI scans). · Previously irradiated lesions may be considered to be measurable provided: 1) there has been documented progression of the lesion(s) since completion of radiotherapy, and 2) the criteria for measurability as outlined above are met. 3. ECOG performance status ≤1 4. Minimum life expectancy of 3 months 5. Adequate renal and hepatic function, defined as: · Total serum bilirubin ≤ 1.5 x ULN for the institution · AST and/or ALT ≤ 3 x ULN for the institution (≤ 5 x ULN if liver metastases are present) · Serum albumin ≥ 2.5 g/dL · Serum Creatinine ≤1.5 x ULN for the institution (or a calculated creatinine clearance ≥ 50 mL/min/1.73m2) 6. Adequate bone marrow function, defined as: · ANC ≥ 1.5 x 10^9/L · Platelet count ≥ 100 x 10^9/L 7. Serum cholesterol <350 mg/dL and triglycerides < 400 mg/dL 8. Male and female patients who are not surgically sterile or postmenopausal must agree to use reliable methods of birth control for the duration of the study until 30 days after the last dose of study drug 9. Able to understand and give written informed consent
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E.4 | Principal exclusion criteria |
1. Women who are pregnant or lactating 2. Presence of brain metastases 3. Prior therapy with rapamycin, rapamycin analogues or tacrolimus 4. Prior anticancer treatment (chemotherapy, radiotherapy, hormonal, immunotherapy, biologoical response modifiers, signal transduction inhibitors, etc) within 4 weeks prior to the first dose of AP23573; the interval is ≥ 2 weeks for signal transduction inhibitors with a half-life known to be <24 hours, and is ≥ 6 weeks for nitrosourea or mitomycin. The following exceptions are allowed: · hormonal therapy (e.g., Megace) for appetite stimulation · nasal, ophthalmic, and topical glucocorticoid preparations · a stable dose of corticosteroids for at least two weeks · low dose maintenance steroid therapy for other conditions · physiologic hormone replacement therapy (e.g., thyroid supplementation for thyroid deficiency or oral replacement glucocorticoid therapy for adrenal insufficiency) 5. Ongoing toxicity associated with prior anticancer therapy (except peripheral neuropathy of ≤ grade 1 by NCI toxicity criteria) 6. Another primary malignancy within the past three years (except for non-melanoma skin cancer and cervical carcinoma in situ) 7. Known or suspected hypersensitivity to drugs formulated with polysorbate 80 (Tween) or any other excipient contained in the study drug 8. Known Grade 3 or 4 hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin) 9. Significant uncontrolled cardiovascular disease 10. Active infection requiring systemic therapy 11. Known HIV infection 12. Treatment with any investigational agent within 4 weeks prior to the first dose of AP23573 13. Concurrent treatment with immunosuppressive agents other than prescribed corticosteroids at stable doses for ≥ 2 weeks prior to first planned dose of study drug 14. Inadequate recovery from any prior surgical procedure or having undergone any major surgical procedure within 2 weeks prior to the first dose of AP23573 · Patients having undergone recent placement of a central venous access port will be considered eligible if they have recovered 15. Presence of any other life-threatening illness or organ system dysfunction which, in the opinion of the Investigator, would either compromise the patient’s safety or interfere with evaluating the safety of the study drug
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E.5 End points |
E.5.1 | Primary end point(s) |
Complete or partial response or prolonged stable disease ≥ 16 weeks duration, as assessed using modified RECIST guidelines. |
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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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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) | 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 | No |
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 | 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 | 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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The end-of-trial (completion) date is when all patients have completed all study visits or have otherwise discontinued from the study. |
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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 | 10 |
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 | 10 |