E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
advanced or metastatic soft tissue sarcoma relapsing after anthracycline/ifosfamide-based chemotherapy regimen |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10041129 |
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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 |
To assess the antitumor activity of single agent gimatecan given orally on a 5 consecutive days schedule every 28 days as salvage treatment in patients with advanced or metastatic soft tissue sarcoma pretreated with anthracycline / ifosfamide-based chemotherapy. |
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E.2.2 | Secondary objectives of the trial |
- To assess activity according to a Bayesan model, to specifically address the behaviour of the different histologic sub-types. - To evaluate the activity based on time to event and time related parameters. - To define the safety profile of gimatecan therapy given orally for 5 consecutive days every 28 days. - To define patients adherence to gimatecan therapy given orally for 5 consecutive days every 28 days. - To perform pharmacokinetics evaluations. - To perform optional Translational Medicine evaluations, described in an ancillary protocol. These evaluations will be done only in consenting patients, signing a separate informed consent form. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Soft Tissue Sarcoma relapsing after anthracyclines and ifosfamide based chemotherapy. Only the following subtypes of soft tissue sarcoma should be included: Fibrosarcoma Leiomyosarcoma Liposarcoma Malignant fibrous histiocytoma Rhabdomyosarcoma Ewing’s Sarcoma of Soft Tissue Synovial sarcoma Angiosarcoma/hemangiopericytoma Malignant peripheral nerve sheath tumor (MPNST) Sarcoma - unclassified Mesenchymal chondrosarcoma Extraskeletal myxoid chondrosarcoma (provided that it is metastatic disease which cannot be surgically treated)
2. Patients must have received previous chemotherapy regimens for unresectable advanced or metastatic disease, including anthracyclines and ifosfamide. A maximum of three prior lines is permitted (including adjuvant). Anthracyclines and ifosfamide may have been administered simultaneously or in successive lines of therapy, but the patient should have received both. 3. Clear progressive disease. In case of prior adjuvant therapy progression should have occurred during adjuvant therapy or within 24 months of completion of adjuvant therapy. 4. Age > 18 years. 5. ECOG performance status < 1. 6. Adequate hematological function: hemoglobin > 9 g/dl; neutrophils > 1.5 x 109/L; platelets > 150 x 109/L; 7. LVEF > 50% evaluated by means of ultrasound 8. Adequate liver and renal function - alkaline phosphatase £ 1.5 x UNL, if bone metastases present, hepatic isoenzyme should be <1.5 UNL - total serum bilirubin £ 1.5 times UNL regardless of liver involvement secondary to tumor - ALT, AST £ 1.5 x UNL (£ 2.5 x UNL in presence of liver metastases)- albumin > 2.5 g/dl - creatinine £ 1.5mg/dL 9. All previous therapies to treat sarcoma must have been discontinued > 4 weeks before study entry and all acute toxicities (excluding alopecia) of any prior therapy must have resolved to CTCAE (Version 3.0) Grade ≤1. 10. Life expectancy of at least 3 months. 11. Evidence of a signed and dated informed consent document indicating the patient (or legally acceptable representative) has been informed of all pertinent aspects of the study 12. Willingness and ability to comply with the study protocol for the duration of the trial. |
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E.4 | Principal exclusion criteria |
1. The following sarcomas are NOT eligible: - Gastrointestinal stromal sarcoma (GIST) - Osteosarcoma of soft tissue - Chondrosarcoma (with the exception of mesenchymal chondrosarcoma and extraskeletal myxoid chondrosarcoma (metastatic disease which cannot be surgically treated))) - Carcinosarcomas (mixed Mullerian tumors) - Kaposi sarcoma - Malignant mesothelioma - Clear cell sarcoma 2. Prior radiation therapy to > 30% red bone marrow 3. Active infection. 4. Any investigational agent received ≤ 4 weeks prior to study entry and/or concurrent enrolment in another clinical trial. 5. Any prior topotecan- or irinotecan - containing regimen or any regimen containing an investigational inhibitor of topoisomerase I. 6. Prior high dose chemotherapy treatment requiring hematopoietic stem cell rescue. 7. Previous major gastrointestinal surgery or diseases that could alter absorption or motility (i.e. active peptic ulcer, inflammatory bowel disease, known intolerance to lactose, malabsorption syndromes, intestinal sub-occlusion or previous major gastrointestinal surgery). 8. Inability to swallow 9. Presence of serious cardiac (congestive heart failure, angina pectoris, myocardial infarction within one year prior to study entry, uncontrolled hypertension or arrhythmia), neurological or psychiatric disorder. 10. Presence of uncontrolled intercurrent illness or any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study. 11. Previous concomitant malignancy at other site, other than basal or squamous cell carcinoma of the skin or in situ cervical carcinoma within 5 years. 12. Symptomatic brain metastases or leptomeningeal disease requiring therapy. 13. Pregnancy or lactation or unwillingness to use adequate method of birth control |
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E.5 End points |
E.5.1 | Primary end point(s) |
Response Rate observed after gimatecan treatment, administered orally for 5 consecutive days every 28 days. |
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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 | 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 | 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 | 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.8.5 | 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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The treatment can be continued until evidence of progressive disease, occurrence of toxicity, or patient refusal, at the discretion of the investigator. |
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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 | |
E.8.9.1 | In the Member State concerned months | 15 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 15 |