INOVATYON

Phase III international, randomized study of Trabectedin plus Pegylated Liposomal Doxorubicin (PLD) versus Carboplatin plus PLD in patients with ovarian cancer progressing within 6-12 months of last platinum.

Doel:
Onderzoeken of PLD trabectedine effectiever is dan PLD carboplatin en of door het uitstel van het gebruik van carboplatin de gevoeligheid van platina toeneemt, waardoor ook de 2e PFS na behandeling verlengd wordt

Inclusion Criteria:

  • Female, aged ≥ 18 years
  • Histologically and/or cytologically proven epithelial ovarian, epithelial fallopian tube cancer or primary peritoneal cancer
  • Progression free interval between six and twelve (6-12) months (calculated from the first day of the last cycle of the last platinum-based chemotherapy until the date of progression confirmation through radiologic imagery). Patients may have received up to two platinum-based chemotherapy lines, of which at least one must have contained a taxane
  • Measurable or evaluable disease confirmed by radiological imaging, such as magnetic resonance imaging (MRI), computed tomography (CT) scan, or PET/CT scan at study entry (CA-125 rise not supported by radiological evidence of disease is not accepted as criteria for defining progression) or histological proven recurrent ovarian cancer even in the absence of postoperatively measurable or evaluable lesions.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2
  • Estimated life expectancy ≥ 12 weeks
  • Patients must be accessible for treatment and follow-up
  • Adequate organ function within 14 days prior to first cycle as evidenced
  • Patients must be able to receive dexamethasone or its equivalent, which is required if randomly assigned to treatment with trabectedin plus PLD
  • Informed consent of the patient

Exclusion Criteria:

  • Non epithelial ovarian or mixed epithelial/non epithelial tumors (e.g., Mullerian tumors)
  • Patients who did not respond to last platinum-based therapy or in whom last relapse occurred < 6 months or > 12 months from the last dose of platinum
  • Bowel obstruction, sub-occlusive disease or the presence of symptomatic brain metastases
  • Pre-existing grade > 1 motor or sensory neuropathy according to the National Cancer Institute Common Toxicity Criteria Adverse Event (NCI-CTCAE) version 4.0
  • Myocardial infarct within six months before enrolment, New York Association (NYHA) Class II or worse heart failure (Appendix 1. The New York Heart Association), uncontrolled angina, severe uncontrolled ventricular arrythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
  • History of liver disease
  • Concurrent severe medical problems or any unstable medical condition unrelated to malignancy, which would significantly limit full compliance with the study or expose the patient to extreme risk or decreased life expectancy
  • Breastfeeding women and women of child bearing potential must use effective contraception during treatment and 3 months thereafter, which may include prescription contraceptives (oral, injection, or patch), intrauterine device, double-barrier method or male partner sterilization (not applicable to patients that are surgically sterile)
  • Prior exposure to trabectedin
  • Prior resistance to anthracyclines or PLD defined as a progression during anthracycline-based chemotherapy or a recurrence within 6 months from its ending
  • Prior severe PLD related toxicity
  • Prior exposure to cumulative doses of doxorubicin >400mg/m2 or epirubicin >720mg/m2
  • Treatment with any investigational product within 30 days prior to inclusion in the study

Randomisatie

Arm A: PLD 30 mg/m2 and carboplatin AUC 5 q 4 wx6
Arm B: PLD 30 mg/m2 and trabectedin 1.1 mg/m2q3wx6

Aanvullende onderzoeken bij randomisatie of follow-up
MUGA en QOL

Follow-up schema
Elke 12 weken anamnese, lich onderzoek, adverse events, CA125 en CT

Deelnemende Centra:
Academisch Medisch Centrum
Maastricht UMC
UMC Utrecht
Radboud UMC

Contactpersonen
P.B. Ottevanger 024-3610353
A.M. Westermann: e-mail:  secr-onco@amc.nl

Controle factsheet: maart 2017