E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Soft tissue sarcomas are a family of malignant diseases originating from mesenchymal cells. Two types of theses sarcomas, dermatofibrosarcoma protuberans (DFSP) and giant cell fibriblastoma(GCF), are rare invasive tumors of the dermis which possess intermediate malignancy, of which surgical removal is presently the sole effective treatment. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057070 |
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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 principal objective of the trial is to assess the therapeutic activity of imatinib (Glivec) in patients with locally advanced and/or metastatic soft tissue sarcomas expressing COL1A1/PDGF beta rearrangement i.e. DFSP and GCF. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to characterize the safety of Glivec in patients with locally advanced and/or metastatic DFSP and GCF expressing COL1A1/PDGF-beta rearrangement. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
♦ Patients must have histologically proven locally advanced or metastatic DFSP or GCF. In case of metastatic disease, tissue can be taken either from the primary tumor or from the metastasis provided the biopsy can be taken without mutilating surgery. ♦ Patients must have been evaluated by a multidisciplinary team (medical oncologist, surgical oncologist) before entering in the trial. ♦ Patients must have DFSP or GCS not amenable to surgery, radiation or combined modality treatment with curative intent. Palliative radiation therapy is permitted provided it will not be given to a target lesion. ♦ Patients must have measurable disease, as defined in the RECIST criteria (see chapter on "Response evaluation"). ♦ Patient’s tumor surroundings must be marked on the skin after the surroundings have been optionally identified by ultrasound. This marking should be done using tatouage technique. ♦ Patient must have progressive disease documented in the last 3 months. ♦ Patients must have frozen tumor or paraffin embedded tissue available for immunohistochemical and molecular analysis and for central review of eligibility. ♦ Patients must have WHO performance status <=2. ♦ Patients must be >=18 years. ♦ Patients have been either not pretreated with chemotherapy or with no more than one line of combination chemotherapy with ifosfamide and doxorubicin or 2 lines of single agent therapy or be relapsing within 6 months after the end of adjuvant chemotherapy. ♦ The patient must not have received chemotherapy, biologic therapy or any other investigational drug for any reason within 28 days prior to treatment start. ♦ Patients previously irradiated on the lesion must have progressive disease and irradiation should have been stopped for at least six months. ♦ No concomitant treatment with other cytostatic agents or tyrosine kinase inhibitors. ♦ Patient must have adequate liver function as defined by a serum bilirubin ≤ 1.5 x the institutional upper limit of normal (IULN), SGOT or SGPT ≤ 2.5 x the institutional upper limit of normal (or ≤ 5 x the institutional upper limit of normal if hepatic metastases is present) obtained within 14 days prior to first registration. ♦ Patient must have an adequate renal function as defined by a serum creatinine ≤ 1.5 x the institutional upper limit of normal obtained within 14 days prior to first registration. ♦ Patient must have absolute neutrophil count (ANC) ≥ 2.0x109/l and a platelet count ≥ 100x109/l obtained within 14 days prior to first registration. Baseline hemoglobin must be ≥ 9 g/dl (this may be achieved by transfusion if needed). ♦ Patient may not have a severe and/or uncontrolled concurrent medical disease (e.g., uncontrolled diabetes, uncontrolled chronic renal or liver disease, or active uncontrolled infection, e.g., HIV). ♦ Patient must not be pregnant or nursing. Women/men of reproductive potential must agree to use an effective contraceptive method throughout the study and for up to 3 months following discontinuation of study drug. Women of reproductive potential must have a negative serum pregnancy test within 7 days prior to treatment start. Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. ♦ No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years. ♦ Patient must not be taking therapeutic doses of coumarine derivatives as anticoagulation. Patients requiring therapeutic anticoagulation may use low-molecular weight heparin, and minidose coumarine derivatives (equivalent to Coumadin 1 mg po QD) is allowed as prophylaxis. ♦ Before patient registration, written informed consent must be given on the EORTC informed consent sheath according to ICH/GCP, and national/local regulations. ♦ Patients must have given consent that in the case of absence of progression or unaccepted toxicity, they will be treated with Glivec for minimum of 14 weeks, and that no surgical resection will be performed within 14 weeks after treatment start. ♦ Patient with medical or psychological, familial, sociological or geographical conditions that, in the opinion of the investigator, make the patient unable to tolerate or complete the treatment, to comply with the study protocol and follow-up schedule or to grant reliable informed consent are not eligible for this study. Those conditions should be discussed with the patient before registered in the trial.
♦ All patients must have tumor expressing COL1A1/PDGF-beta as evaluated on paraffin embedded or fresh frozen tumor tissue using the cytogenetic technique FISH. Eligibility for the second registration is based on evaluation by the central reviewer. |
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E.4 | Principal exclusion criteria | |
E.5 End points |
E.5.1 | Primary end point(s) |
The 14 weeks progression free survival (taken as a binary variable) has been chosen as primary endpoint. Success will be defined as absence of progression after at least 14 weeks of therapy. |
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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 | No |
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 | 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 | No |
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 | No |
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 | 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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Dependent - Treatment should be administered for at least 14 weeks until documented disease progression, unacceptable toxicity or patient refusal. |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |