| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Female subjects 18 years of age or older with advanced ovarian cancer who have met the specific inclusion and exclusion criteria will be enrolled in this study. Subjects must have histologically proven epithelial ovarian or primary peritoneal cancer previously treated with only 1 chemotherapy regimen (platinum-based) and have experienced either recurrence or progression more than 6 months after the beginning (first dose) of the initial line of platinum-based chemotherapy for ovarian cancer. |
|
| 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 |
|
| 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 (trabectedin) for intravenous infusion + DOXIL/CAELYX (doxorubicin HCl liposome injection, hereafter referred to as DOXIL) improves overall survival (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 (trabectedin) for intravenous infusion + DOXIL/CAELYX improves progression free survival (PFS) over DOXIL alone in the management of ovarian cancer in second line therapy. |
|
| E.2.2 | Secondary objectives of the trial |
| Secondary objectives are to demonstrate an increase of objective response rate (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. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
| 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 or primary peritoneal cancer Prior treatment with only one chemotherapy regimen (including adjuvant therapy), which must be platinum-based and may include sequential maintenance therapy (no gaps in administration of initial therapy may occur other than a delay no longer than 1 cycle for treatment toxicity). Eastern Cooperative Oncology Group performance status is equal or less than 2 Estimated life expectancy of at least 3 months Recurrence or progression after 6 full cycles of a complete 6 cycle initial treatment regimen or 6 months after the beginning (first dose) of the initial treatment line of platinum-based chemotherapy for ovarian cancer to include − Platinum-resistant subjects (platinum-free interval from the end of first-line treatment less than 6 months) − Platinum-sensitive subjects (platinum-free interval from the end of first-line treatment equal or more than 6 months) who are not expected to benefit from or who are ineligible for or who are not willing to receive retreatment with platinum-based chemotherapy Measurable or non-measurable disease that can be evaluated by response evaluation criteria in solid tumors (RECIST) for response and/or progression and documented by radiographic methods such as magnetic resonance imaging (MRI) or computed tomography (CT) scan. Date of radiological evidence is the documented date of progression For subjects with non-measurable disease, in addition to appropriate imaging, CA-125 level 2 X upper limit of normal (ULN) on at least 2 measurements more than 1 week apart, the second assessment during the screening phase of this study (performed by central lab) Must be able to receive dexamethasone or its equivalent 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 CPK ≤ ULN Hepatic function variables Total bilirubin ≤ 1.5 ULN, direct bilirubin ≤ ULN Total alkaline phosphatase ≤ 1.5 ULN, or if > 1.5 ULN, then alkaline phosphatase liver fraction or 5’ nucleotidase must be ≤ ULN AST and ALT must be ≤ 2.5 x ULN Left ventricular ejection fraction (LVEF) by baseline MUGA scan or 2 d echocardiogram must be within normal limits for the institution (if required at baseline, see section 6.2.2) 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 optional CellSearch, pharmacogenomic, or protein testing portion of this protocol, the subject (or their legally acceptable representative) must sign the informed consent forms for CellSearch enumeration alone, or for additional pharmacogenomic testing, utilizing CellSearch, additional blood or paraffin samples or serum for DNA, mRNA, and protein expression analysis. These informed consent documents will indicate whether or not the subject wishes to participate in these parts of the study. Participation in the pharmacogenomics and CellSearch aspects of this study is not mandatory. |
|
| E.4 | Principal exclusion criteria |
| 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 for ovarian cancer or to YONDELIS or hypersensitivity to the pharmacologically active substance or to any of the excipients Subjects unwilling or unable to have a central venous catheter (which is required if randomized to treatment with YONDELIS + DOXIL combination arm) Subjects of child-bearing potential not employing adequate contraception which may include prescription contraceptives (oral, injection, or patch), intrauterine device, double-barrier method or male partner sterilization (not applicable to subjects that are surgically sterile) or subjects who are lactating. 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 hypersensitivity to doxorubicin or to excipients in the formulations of either DOXIL or YONDELIS. Known clinically relevant CNS 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, 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 (including dementias) that prevents compliance with protocol − Uncontrolled seizures − Acute deep vein thrombosis requiring intravenous or subcutaneous therapeutic anticoagulant therapy (chronic coumadin or prophylactic subcutaneous heparin allowed) − Active infection |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint, OS, is defined as the time between the date of randomization and the date of death. Subjects who die, regardless of the cause of death, will be considered to have had an event. Subjects who withdraw consent for the study will be censored at the time of withdrawal. Subjects who complete the study and are still alive at the time of the clinical data cut-off date will be censored. All subjects who were lost to follow-up prior to the clinical data cut-off date will also be censored at the time of last contact. OS will be compared between both treatment arms by the unstratified log rank test. Another key primary endpoint, PFS, is defined as the time between the date of randomization and the date of disease progression or death. This analysis will utilize the determination of progression date documented by central review (Section 11.4.5). Subjects who progressed or died will be considered to have had an event. Subjects who complete the study without disease progression will be censored at the last tumor assessment prior to end of the study. Subjects who are lost to follow-up without disease progression will be considered censored at the time of last tumor assessment. PFS will be compared between both treatment arms by the un-stratified logrank test. |
|
| 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 | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | Information not present in EudraCT |
| 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 | 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 | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Yondelis + Doxil/Caelyx vs Doxil/Caelyx |
|
| 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 |
|
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
Print
