E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ovarian Cancer; Stage FIGO IIIc and IV with more than 500 ml ascites |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057529 |
E.1.2 | Term | Ovarian cancer metastatic |
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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 |
progression free survival (PFS) between subjects treated with sorafenib in combination paclitaxel and carboplatin compared versus historic patient collective |
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E.2.2 | Secondary objectives of the trial |
• Evaluation of overall survival (OS) • Evaluation of Time to treatment failure (TTF) • Evaluation of response rates and duration of response • Evaluation of six and twelve month relapse rate post chemotherapy • Evaluation of quality of life (EORTC-QLQC30 / QLQ-OV28) • Evaluation of toxicity, safety and tolerability • Evaluation of tumor mass post surgery • Evaluation of ascites reduction pre surgery • Evaluation of biomarker (histological and peripheral) • Evaluation of tumor cell RNA expression, proteomic pattern • Evaluation of mineral metabolism |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
o Written informed consent prior to any study specific screening procedures with the understanding that the patient has the right to withdraw the consent without the need to specify a respective reason o Histological confirmed primary epithelial ovarian cancer carcinoma of the fallopian tubes and extra ovarian peritoneal carcinoma stage FIGO IIIC or IV, verified by laparoscopy or laparotomy o More than 500 ml ascites (verified by ultrasound or ct-scan) o Female patients with age higher or equal to 18 years o Life expectancy of at least 12 weeks o Patients who have an ECOG performance status of less or equal 2 o Adequate bone marrow, renal and hepatic function, assessed by the following laboratory investigations at screening: o Hemoglobin ≥ 8 g/dl o Absolute neutrophile count 1,500/ mm³ o Thrombocytes 100,000/ μl o Bilirubine total 1,5 x ULN o ALT and AST 2,5 x ULN o Alkaline phosphatase (AP) 6.0 x ULN o Serum creatinine 1,5 x ULN o Estimated GFR (by Jeliffe) 60 ml / min o Amylase and lipase 1.5 x ULN o PT or INR and PTT 1.5 x ULN
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E.4 | Principal exclusion criteria |
o Patients with a history of other malignancies during the past 3 years, with the exception of adequately treated basal or squamous-cell skin cancer, or cervical carcinoma o Major surgery within 4 weeks of enrolment, or major debulking surgery without any time limit o Patients with symptoms of ileus o Known history of HIV infection or chronic hepatitis B or C infection o Active serious bacterial or fungal infections (> grade 2 NCI-CTCAE, Version 3.0) o History of cardiac disease: congestive heart failure >NYHA class 2, active CAD (coronary artery disease) (MI more than 6 months prior to study entry is allowed); cardiac arrhythmia requiring and arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension o Patients undergoing renal dialysis o Patients with evidence or history of bleeding diathesis o History of motorial and sensorial neuropathic disorders equal or higher than grade 2 o Known neoplastic central nervous system abnormality. Patients with neurological symptoms should undergo CT scan/MRI of the brain to exclude brain metastasis o Manifest depression o Known or suspected allergy to the investigational agent or any agent given in association with this trial o Patients with seizure disorder requiring medication o History of organ allograft o Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study o Pregnant or breastfeeding patients: Women with childbearing potential must have a negative pregnancy test performed within 7 days prior to the start of the study drug o Patients enrolled in this trial must use adequate barrier contraceptive measures during the course of the trial until hysterectomy in ‘Debulking surgery’ was performed o Any prior systemic anticancer therapy including chemotherapy, targeted agents, experimental therapy, endocrine therapy radiotherapy or biological therapy o Concurrent anticancer chemotherapy or immunotherapy. o Concurrent treatment with systemic corticosteroids, except antiemetic. o Investigational drug therapy outside of this trial during or within 4 weeks of study entry o Patients receiving immunotherapy, radiation therapy, chemotherapy, or other investigational agents within 30 days prior to the first study drug administration o Patients unable to swallow oral medications o Concomitant administration of: o Rifampicin o St. John´s Wort (hypericum perforatum; DE: Johanniskraut)
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E.5 End points |
E.5.1 | Primary end point(s) |
progression free survival (PFS) |
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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 | 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) | 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.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
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 | 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 | 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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chemotherapy phase with debulking surgery: A maximum of 22 weeks Maintenance phase (only with sorafenib): 56 weeks Follow up: 2 years |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
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 |