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

• Comparing the Overall survival (OS) of patients in the combination arm of trabectedin + DOXIL with DOXIL monotherapy arm [ Time Frame: Until death or Clinical cutoff (end of data collection for study) ] [ Designated as safety issue: Yes ]
• Comparing the Objective Response Rate (ORR) of patients in the combination arm of trabectedin + DOXIL with DOXIL monotherapy arm [ Time Frame: Until disease progression or death ] [ Designated as safety issue: No ]
• Comparing the number of patients with adverse events in the combination arm of trabectedin + DOXIL with DOXIL monotherapy arm [ Time Frame: Until 30 days from the last study medication administration or death ] [ Designated as safety issue: Yes ]
• Characterize the pharmacokinetics of trabectedin and DOXIL in patients of the combination arm of trabectedin + DOXIL with DOXIL monotherapy arm [ Time Frame: Up to Day 15 of Cycle 2 ] [ Designated as safety issue: No ]

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.

• Drug: Trabectedin
  Type=exact number, unit=mg/m2, number=1.1, form=solution, route=IV. Trabectedin will be administered over 3 hours every 3 weeks.
  Other Name: Yondelis
• Drug: DOXIL
  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.
  Other Name: CAELYX
• Drug: Dexamethasone
  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.
  Other Name: Dexamethasone

• Experimental: DOXIL + trabectedin
  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.
  Interventions:

  • Drug: Trabectedin
  • Drug: DOXIL
  • Drug: Dexamethasone
• Active Comparator: DOXIL
  Monotherapy arm - DOXIL: 50 mg/m2 IV infusion over 90 minutes every 4 weeks.
  Intervention: Drug: DOXIL

• Krasner CN, Poveda A, Herzog TJ, Vermorken JB, Kaye SB, Nieto A, Claret PL, Park YC, Parekh T, Monk BJ. Patient-reported outcomes in relapsed ovarian cancer: results from a randomized Phase III study of trabectedin with pegylated liposomal doxorubicin (PLD) versus PLD alone. Gynecol Oncol. 2012 Oct;127(1):161-7. doi: 10.1016/j.ygyno.2012.06.034. Epub 2012 Jul 2.
• Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, Pujade-Lauraine E, Park YC, Parekh TV, Poveda AM. Trabectedin plus pegylated liposomal doxorubicin (PLD) versus PLD in recurrent ovarian cancer: overall survival analysis. Eur J Cancer. 2012 Oct;48(15):2361-8. doi: 10.1016/j.ejca.2012.04.001. Epub 2012 Apr 26.

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