E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced relapsed ovarian cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 5.0 |
E.1.2 | Level | DT |
E.1.2 | Classification code | 10033130 |
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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 primary objective of the study is to demonstrate that the combination of YONDELIS + DOXIL improves OS over DOXIL alone in the management of ovarian cancer in second line therapy.
Another key primary objective of the study is to demonstrate that the combination of YONDELIS + DOXIL improves PFS over DOXIL alone in the management of ovarian cancer in second line therapy.
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to demonstrate an increase of ORR and to compare the safety profiles of the combination and monotherapy with DOXIL alone. The pharmacokinetics of DOXIL and YONDELIS in each treatment group will be characterized. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Subjects must satisfy all of the following criteria to be enrolled in the study:
· Female, age 18 or older · Histologically proven epithelial ovarian cancer · Prior treatment with only 1 chemotherapy regimen (including adjuvant therapy) · No previous exposure to anthracyclines or YONDELIS · Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 · Recurrence or progression more than six months after the beginning (first dose) of the initial line of platinum-based chemotherapy for ovarian cancer · Measurable or non-measurable disease that can be evaluated by response evaluation criteria in solid tumors (RECIST) criteria for response and/or progression and documented by radiographic methods such as magnetic resonance imaging (MRI) or computed tomography (CT) scan · For subjects with non-measurable but evaluable disease, CA-125 level 2 x upper limit of normal (ULN) on at least 2 measurements at least 1 week apart, the second assessment prior to inclusion in this study · Adequate organ function as evidenced by the following peripheral blood counts or serum chemistry values within 7 days prior to randomization: - hemoglobin ≥9 g/dL - absolute neutrophil count (ANC) ≥1,500/µL, and - platelet count ≥100,000/µL - serum creatinine ≤ 1.5 mg/dL (<132.6 µmol/L) or creatinine clearance ≥60 mL/min · Hepatic function variables - Total bilirubin ≤ 1.5 - Total alkaline phosphatase ≤ 1.5 ULN, or if >1.5 ULN, then alkaline phosphatase liver fraction must be ≤ ULN AST and ALT must be ≤ 2.5 x ULN · If cardiac history, left ventricular ejection fraction (LVEF) within normal limits for the institution · Adequately recovered from the acute toxicity of any prior treatment · Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. · At investigative sites that are participating in the CellSearch™ or genomic testing portion of this protocol, the subject (or their legally acceptable representative) must sign the informed consent forms for genetic testing and CellSearch™, indicating whether or not subjects wish to participate in these parts of the study. Participation in the pharmacogenomics and CellSearch aspects of this study is not mandatory.
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E.4 | Principal exclusion criteria |
Potential subjects who meet any of the following criteria will be excluded from participating in the study:
· Subjects treated with more than 1 prior chemotherapy regimen (including adjuvant therapy) · Refractory disease, defined as disease progression within six months of the beginning (first dose) of the initial line of platinum-based chemotherapy for ovarian cancer · Isolated rise in CA-125 without documented radiological evidence of disease progression · Prior exposure to anthracyclines or YONDELIS · Subjects unwilling or unable to have a central venous catheter · Subjects of child-bearing potential not employing adequate contraception · Less than 4 weeks from radiation therapy or last dose of hormonal therapy, biological therapy, therapy with any investigational agent, or chemotherapy. · History of another neoplastic disease (except basal cell carcinoma or cervical carcinoma in situ adequately treated) unless in remission for 5 years or more · Known leptomeningeal metastasis · Active viral hepatitis or history of liver disease · Myocardial infarct within 6 months before enrollment, New York Heart Association (NYHA) Class II or greater heart failure (Attachment 1), uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities. · Any other unstable medical conditions, such as: - Uncontrolled diabetes - Psychiatric disorder that prevents compliance with protocol including dementia - Uncontrolled seizures - Acute deep vein thrombosis requiring intravenous or subcutaneous anticoagulant therapy - Active infection
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of the study is to demonstrate that the combination of YONDELIS + DOXIL improves OS over DOXIL alone in the management of ovarian cancer in second line therapy.
Another key primary objective of the study is to demonstrate that the combination of YONDELIS + DOXIL improves PFS over DOXIL alone in the management of ovarian cancer in second line therapy.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of life relationship between circulating tumor cells (CTCs) and efficacy |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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 | Yes |
E.8.1.6 | Cross over | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
combination against comparator (Caelyx) |
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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.8.5 | 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 | 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 | 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |