E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced unresectable or metastatic soft tissue sarcoma. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10041299 |
E.1.2 | Term | Soft tissue sarcomas |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 research objective is to compare the efficacy and effectiveness of gemcitabine and docetaxel with that of doxorubicin. |
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E.2.2 | Secondary objectives of the trial |
-To compare the efficacy and effectiveness of gemcitabine and docetaxel with doxorubicin using additional endpoints. -To compare the toxicity observed with the two treatment regimens -To compare the quality of life of patients treated with gemcitabine and docetaxel with those treated with doxorubicin -To compare the cost-effectiveness of the two treatment regimens -To investigate the influence of pharmacogenomic profiles of patients on disease response and treatment toxicity of the two treatment regimens (whether patients have specific genes that may cause them to process drugs such that they experience more or less toxicity). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Locally advanced or metastatic soft tissue sarcoma, incurable by surgery or radiotherapy •Histological confirmation of high grade disease (Trojani grade 2 or 3 sarcoma) •Prior to trial enrolment, patients must have evidence of disease progression. Disease progression is defined as radiological progression when comparing current imaging to a prior disease assessment carried out within the previous 6 months. Some patients may present with evidence of clinical progression for whom there is concern regarding treatment delays incurred by awaiting radiological disease progression prior to trial entry – these cases must be discussed with the Chief Investigator to determine eligibility •No prior chemotherapy regimen for sarcoma and no prior doxorubicin containing regimen for any previously treated cancer •WHO performance status 0 – 2 •Age ≥13 years •Histological material available for central review (see section 8.7) •Measurable disease evaluable by RECIST criteria version 1.1. New lesions occurring in previously irradiated fields, and progression of previously irradiated lesions, will be eligible •Life expectancy of at least 3 months •Adequate organ function: Neutrophils ≥1.0 x 10*9/L Platelets ≥100 x 10*9/L Bilirubin ≤1.5 x upper limit of normal (ULN) AST or ALT ≤3.0 x ULN ALP ≤3.0 x ULN, if ALP ≥ 3.0 x ULN, patients can be entered if this is shown to be bone isoenzyme Measured or calculated creatinine clearance ≥30 ml/min Ejection fraction (measured according to local practice) within normal limits for the site •Patients to agree to use contraception for the duration of the trial, where applicable (see section 5.3.3) •Able to complete quality of life questionnaires •Able to give informed consent |
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E.4 | Principal exclusion criteria |
•Soft tissue sarcoma of the following types: Alveolar soft part sarcoma Gastrointestinal stromal tumour Ewing’s sarcoma family of tumours Alveolar or embryonal rhabdomyosarcoma Desmoplastic small round cell tumour Extra-skeletal myxoid chondrosarcoma Dermatofibrosarcoma protruberans Malignant mixed mesodermal tumour/carcinosarcoma of the uterus Smooth muscle tumours of uncertain malignant potential (STUMP) •Known active/uncontrolled brain metastases •Grade 3 or 4 peripheral neuropathy •Active uncontrolled infection •Prior history of malignancy other than sarcoma, except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, breast or prostate, and unless the patient has been free of malignancy for a period of 3 years prior to first dose of trial drug •Women who are pregnant or lactating •Any serious and/or unstable pre-existing medical, psychiatric or other condition that could interfere with patient safety or obtaining informed consent |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients alive and progression free at 24 weeks after the date of randomisation |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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 | 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) | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 22 |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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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5 years after the last administration of protocol treatment or death of the last surviving patient, whichever is sooner. |
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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |