E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
advanced-stage soft tissue sarcoma treated with cisplatin after failure of anthracycline and ifosfamide chemotherapies. |
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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 |
To compare the progression-free survival (PFS) in the 2 treatment arms |
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E.2.2 | Secondary objectives of the trial |
- To compare the overall survival (OS) in the 2 treatment arms - To compare the objective response rate (RR) in the 2 treatment arms - To assess the safety profile of AVE8062 (in combination with the background cisplatin therapy) - To assess the pharmacokinetics (PK) of AVE8062 and its main metabolite, RPR258063, using a population approach, in all patients enrolled in selected centers. -To assess genotypes of drug metabolizing enzymes in all enrolled patients in blood sampling collected before the first study drug infusion. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histologically proven STS at the first diagnosis. - Unresectable locoregional recurrent OR metastatic soft tissue sarcoma - Failure of a previous anthracycline-based regimen administered at recommended dose and of prior ifosfamide therapy - Disease progression within 1 month before study randomization |
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E.4 | Principal exclusion criteria |
- Patient consent form not obtained, signed and dated - Less than 18 years old - ECOG Performance Status (PS) > 2 - Life expectancy shorter than 12 weeks. - Patients with well controlled primary disease and who are candidates to total surgical resection of metastasis (1 or more lesions) before study randomization. - Brain metastases and carcinomatous leptomeningitis. - More than two previous chemotherapy regimens for advanced disease. - Prior intensive chemotherapy with autologous stem cell rescue - Prior treatment with Tyrosine Kinase inhibitors (TKI) (specific or multitargeted agents) - History of other cancer. Adequately treated basal cell or squamous cell skin cancers, carcinoma in situ of the cervix, or any other cancer from which the patient has been disease free for > 5 years are allowed. - Only lesions previously irradiated (i.e. lesions not evaluable) if no other evaluable lesions are present. At study entry, in the case of one single metastatic target lesion, histological or cytological proof to metastasis should be obtained. - Pregnant or breast-feeding women. Positive serum or urine pregnancy test for women prior to randomization - Patients with reproductive potential (M/F) who do not agree to use accepted and effective method of contraception during the study treatment period and for at least 3 months after the completion of the study treatment. The definition of “effective method of contraception” will be based on the investigator’s judgment. For patients enrolled in the United Kingdom, the following method of contraception are acceptable: Oral contraceptives accompanied by the use of a second method of contraception (as it is not known how oral contraceptives interact with all the study medications) or Intra Uterine Device (IUD) or women who are surgically sterile or women who are post-menopausal or for other reasons have no chance of becoming pregnant. Female partners of male patient must follow the same contraceptive methods as mentioned above. - Washout period of less than 3 weeks from prior anti-tumor therapy (chemotherapy, targeted agents, and radiotherapy) or any investigational treatment, except for nitrosoureas, mitomycin C which may not be used up to 6 weeks prior to the randomization date provided that patients do not have residual signs of any toxicity. - Complete initial work up earlier than 3 weeks prior to patient randomization. - Patient’s inability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. - Concurrent treatment with any other anticancer therapy, including chemotherapy, immunotherapy, radiotherapy, targeted therapy, gene therapy, or patients planning to receive these treatments during the study. - Other severe illness or medical conditions such as and not exhaustive : 1. Active infection. 2. Superior Vena Cava Syndrome. 3. Severe chronic obstructive pulmonary disease (COPD) and/or extensive pulmonary fibrosis (arterial blood gases PAO2 < 60 or non invasive oximetry SaO2 < 90). 4. Pericardial effusion requiring intervention (drainage). 5. Severe proteinuria (Grade 3-4, > 3.5 g/24h). - Patient with LVEF value lower than 50 % for institution inferior normal limit, evaluated by echocardiography, or by radionuclide assessment. - Ischemic event within 1 year prior to study entry including but not limited to: stroke, angor, whatever the anatomical site, diagnosis of at least one symptomatic coronary insufficiency - Uncontrolled hypertension - Uncontrolled arrhythmia particularly severe conduction disorder such as second or third-degree atrio-ventricular block - Thrombo-embolism requiring anticoagulants within the past 6 months. 1. Blood marrow: neutrophils < 1.5 x 109/L; platelets <100 x 109/L 2. Kidney function: creatinine > 1.5 mg/dl. If creatinine ≥ 1.5 mg/dl, the calculated creatinine clearance should be ≥ 60 ml/min (Cockroft-Gault Formula). 3. Liver function: Total bilirubin value > normal limit; ALT/AST/AP ≥ 2.5 times the upper normal limits of the institutional norms. An increase of AP (≥ grade 2) would be accepted only if this increase is related to the presence of bone metastases. 4. Known platinum hypersensitivity 5. Current peripheral neuropathy > grade 1 according to the NCI CTCAE classification, of any origin including symptoms due to the use of neurotoxic drugs (e.g. vinca-alkaloids, platinum or taxans). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is progression-free survival (PFS) defined as the time interval from the date of randomization to the date of occurrence of the first documented tumor progression or death due to any cause, whichever comes first. An independent review committee (IRC) blinded to the randomization arm and to the patient characteristics, will assess objective radiological tumor progression. |
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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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
All patients will be treated with cisplatin as background therapy |
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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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 | Yes |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |