|This is a randomized, open-label, active-controlled, multicenter study.
Approximately 670 subjects will be enrolled in this study worldwide, with 335 subjects per planned treatment group.
During the Screening Phase, potential subjects will be assessed for study eligibility after providing informed consent to participate in the study. Baseline radiographic disease assessments must be performed within 30 days before randomization.
At randomization, subjects will be stratified by 4 criteria:
1) the time from the last dose of first-line platinum therapy to disease progression (6 months to 12 months vs >12 months to 24 months vs >24 months),
2) Eastern Cooperative Oncology Group (ECOG) performance status grade (0 vs 1),
3) BRCA 1/2 status (mutation vs no mutation), and
4) prior pegylated liposomal doxorubicin therapy (no vs yes). Subjects will then be randomly assigned in a 1:1 ratio to the trabectedin+DOXIL combination therapy group (Arm A) or to the DOXIL monotherapy group (Arm B).
During the Treatment Phase, subjects will receive study drug by IV infusion on Day 1 of a 21-day cycle in Arm A and on Day 1 of a 28-day cycle in Arm B.
Treatment will continue until the occurrence of disease progression or unacceptable treatment toxicity, or until 2 cycles beyond a confirmed complete response.
ICON8 and ICON8B - An international phase III randomised trial of dose-fractionated chemotherapy compared to standard three-weekly chemotherapy, following immediate primary surgery or as part of delayed primary surgery, for women with newly diagnosed epithelial ovarian, fallopian tube or primary peritoneal cancer.
|Most patients respond well to first line treatment, surgery and chemotherapy for ovarian cancer however the majority go on to develop relapsed disease and there is a low survival rate. Therefore there’s a significant need to develop more effective first-line treatments.
Standard first-line chemotherapy is a combination of 2 drugs: carboplatin and paclitaxel, given once every 3 weeks for 6 cycles. However giving these agents weekly may be more effective; this is called dose-fractioned chemotherapy.
In ICON8 two dose-fractioned chemotherapy regimens will be compared with standard carboplatin-paclitaxel. The main outcome measures will be whether dose fractioned chemotherapy extends the time until ovarian cancer relapses (improved PFS) and whether women who receive it live longer (improved overall survival).
Women will be randomised to receive either:
Arm 1 (control Arm): Carboplatin (AUC5b by intravenous infusion over 30-60 minutes) and paclitaxel (175mg/m2 by intravenous infusion over 30 minutes) on day 1 of a 21 day cycle.
Arm 2 (research arm): Carboplatin (AUC5b by intravenous infusion over 30-60 minutes) on day 1 and dose-fractioned weekly paclitaxel (80mg/m2 by intravenous infusion over 1 hour) on day 1, 8 and 15 of a 21 day cycle.
Arm 3 (Research arm): Dose fractioned weekly carboplatin (AUC2 by intravenous infusion over 30-60 minutes) and weekly paclitaxel (80mg/m2 by intravenous infusion over 1 hour) on day 1, 8 and 15 of a 21 day cycle.
Treatment duration for all three arms is 18 weeks.