An Efficacy and Safety Study for Yondelis (Trabectedin) in Patients With Advanced Relapsed Ovarian Cancer

An Efficacy and Safety Study for Yondelis (Trabectedin) in Patients With Advanced Relapsed Ovarian Cancer

An Open-Label Multicenter Randomized Phase 3 Study Comparing the Combination of DOXIL/CAELYX and YONDELIS With DOXIL/CAELYX Alone in Subjects With Advanced Relapsed Ovarian Cancer

The purpose of the study is to compare the progression-free survival (PFS) of the combination of trabectedin + DOXIL with DOXIL monotherapy in patients with ovarian cancer.

This is a multicenter, open-label (all people know the identity of the intervention), randomized (study medication is assigned by chance), Phase 3 study comparing the combination of trabectedin + DOXIL with DOXIL monotherapy in patients with advanced ovarian cancer (who were previously treated and for whom first-line platinum-based chemotherapy regimen has failed). Approximately 650 patients will be randomly assigned to 1 of the treatment arms (DOXIL and DOXIL + trabectedin) over 2 years. At the time of randomization, patients will be stratified on the basis of platinum sensitivity of disease (sensitive or resistant) and baseline Eastern Cooperative Oncology Group performance status score (0 to 1 or 2. Safety will be evaluated on the basis of adverse events, clinical laboratory tests, physical examination, vital signs assessment and cardiovascular safety assessment. An interim analysis of overall survival will be performed in conjunction with progression-free survival analysis during the study. Treatment will be continued until disease progression occurred or until patients experienced a confirmed complete response for at least 2 cycles. Continuation of treatment in select individual patients beyond this study end date will be allowed if the investigator determined that the patient is benefiting from treatment, is eligible to receive further therapy, and consents to treatment. If disease progression has not occurred at treatment termination, then disease assessment will continue every 8 weeks until there is evidence of disease progression or death, or until the clinical data cutoff date, or until the start of first subsequent anticancer therapy, whichever is earlier.

Combination arm - Trabectedin + DOXIL: DOXIL 30 mg/m2 intravenous (IV) infusion over 90 minutes + trabectedin 1.1 mg/m2 IV infusion over 3 hours every 3 weeks. patients will be premedicated with 20 mg dexamethasone or its equivalent IV infusion over 30 minutes prior to the DOXIL infusion.

Type=exact number, unit=mg/m2, number=1.1, form=solution, route=IV. Trabectedin will be administered over 3 hours every 3 weeks.

Type=exact number, unit=mg/m2, number=30, 50, form=solution, route=IV. DOXIL will be administered over 90 minutes every 4 weeks when administered alone (monotherapy) and every 3 weeks when administered with trabectedin.

Type=exact number, unit=mg, number=20, form=solution, route=IV. Dexamethasone or its equivalent will be administered over 30 minutes prior to the DOXIL infusion.

From the date of randomization until the date of disease progression or death, as assessed for approximately 3 years

Percentage of participants who achieved complete response (CR) or partial response (PR) as best overall response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR)= greater than or equal to 30% decrease in the sum of the longest diameter of target lesions and Overall Response (OR) = CR + PR.

From the date of randomization until the date of disease progression or death, as assessed for approximately 3 years

Duration of response was defined only for participants who had complete response or partial response as best overall response. Duration of response was calculated from the date of first documentation of response (not the confirmation) to the date of disease progression or death due to progressive disease.

From the date of first documentation of response to the date of disease progression or death due to progressive disease, as assessed for approximately 3 years

Median simulated area under the curve (AUC) of a 21 day trabectedin profile of participants (of this study) administering trabectedin and doxil, calculated using the trapezoidal rule method. Simulations were based on a dataset created of 1000 participants using the posthoc parameter estimations, derived from the population pharmacokinetic analysis dataset of Trabectedin (Participants=831, with resampling). Plasma concentration-time profiles were simulated up to 504 hour post-dosing using a rich sampling.

Day 1 (Predose; 1.5 hour after start of infusion; 5 minutes, 2 hour and 6 to 20 hour after end of infusion); Day 8 (168 hour after end of infusion); and Day 15 (336 hour after end of infusion) at Cycles 1 and 2

Median simulated maximum plasma concentration (Cmax) at 3 hour of a 21 day trabectedin profile of participants (of this study) administering trabectedin and doxil. The assessment of Cmax was based on a dataset created of 1000 participants using the posthoc parameter estimations, derived from the population pharmacokinetic analysis dataset of Trabectedin (participants=831, with resampling). Plasma concentration-time profiles were simulated up to 504 hour post-dosing using a rich sampling.

Day 1 (Predose; 1.5 hour after start of infusion; 5 minutes, 2 hour and 6 to 20 hour after end of infusion); Day 8 (168 hour after end of infusion); and Day 15 (336 hour after end of infusion) at Cycles 1 and 2

Inclusion Criteria: Histologically proven epithelial ovarian cancer, epithelial fallopian tube cancer, or primary peritoneal cancer Prior treatment with only 1 platinum based chemotherapy regimen Eastern Cooperative Oncology Group status of not more than 2 Progression more than 6 months after the start of initial chemotherapy treatment Exclusion Criteria: Treatment with more than 1 prior chemotherapy regimen Progression within 6 months after starting initial chemotherapy Prior exposure to anthracyclines Unwilling or unable to have central venous catheter Known clinically relevant central nervous system metastasis

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