INOVATYON STUDY -International, Randomized Study in Patients With Ovarian Cancer
- Conditions
- Ovarian Cancer
- Interventions
- Registration Number
- NCT01379989
- Lead Sponsor
- Mario Negri Institute for Pharmacological Research
- Brief Summary
The objective of this multicentric, randomised, Phase III study is to demonstrate superiority, in terms of survival, of trabectedin and Pegylated Liposomal Doxorubicin (PLD) versus carboplatin and PLD in partially-platinum sensitive ovarian cancer patients.
- Detailed Description
Patients will be randomised to:
Arm A: PLD 30 mg/m2 and carboplatin AUC 5; Arm B: PLD 30 mg/m2 and trabectedin 1.1 mg/m2. Patients' characteristics: patients over 18 years of age with advanced, progressive ovarian cancer 6-12 months after completion of first line or second line treatment with platinum-based chemotherapy.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 617
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Carboplatin plus PLD Pegylated Lipoxomal Doxorubicin (PLD) Pegylated Lipoxomal Doxorubicin (PLD) 30 mg/ m2 followed by carboplatin AUC 5. Carboplatin plus PLD Carboplatin Pegylated Lipoxomal Doxorubicin (PLD) 30 mg/ m2 followed by carboplatin AUC 5. Trabectedin plus PLD Pegylated Lipoxomal Doxorubicin (PLD) Pegylated Lipoxomal Doxorubicin (PLD) 30 mg/m2 infusion followed by trabectedin 1.1 mg/m2 infusion. Trabectedin plus PLD Trabectedin Pegylated Lipoxomal Doxorubicin (PLD) 30 mg/m2 infusion followed by trabectedin 1.1 mg/m2 infusion.
- Primary Outcome Measures
Name Time Method Overall survival (OS) This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled This is an event driven study. The study will continue until 442 events have occurred.
- Secondary Outcome Measures
Name Time Method Time to subsequent chemotherapy administration This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint The time from randomization to subsequent chemotherapy counted from the administration of subsequent chemotherapy will be evaluated as an exploratory analysis.
CA-125 serological response This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint CA-125 serological response will be the best response obtained in each arm
OS for Subsequent chemotherapies This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint the overall survival counted from the administration of subsequent chemotherapy until death
Best response to each Subsequent chemotherapy line This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint The best response obtained to each Subsequent chemotherapy line calculated as frequency of patients with CR, PR, SD or PD.
Duration of Response This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint Duration of response: will be calculated from the date of first documentation of response (CR or partial response \[PR\], whichever occurs first) to the date of documented PD or death.
Progression Free Survival (PFS) This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint PFS will be measured from the date of randomization to the date of documented PD or death (regardless of cause of death).
Objective RR This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint Objective RR will be the best response obtained in any evaluation according to RECIST 1.1
PFS for the Subsequent Chemotherapies This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint the progression free survival counted from the administration of subsequent chemotherapy untill disease progression or death whichever occurs first
Frequency of serious adverse events (SAEs) This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint Number of SAEs for each randomization arm
QoL according to the EORTC QLQ-C30 and QLQ-OV28 This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint Two PRO instruments will be administered in this study: the EORTC QLQ-C30 and QLQ-OV28.PRO instruments will be completed by the patient at screening (before randomization) and within four weeks after the 6th cycle or at the time of progression, whichever occurs first.
Frequency of toxicities leading to dose delays This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint Clinical and laboratory toxicities
Frequency of toxicities, graded according to the NCI-CTAE version 4.0 This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint Clinical and laboratory toxicities
Frequency of toxicities leading to treatment discontinuation This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint Clinical and laboratory toxicities
Frequency of toxicities leading to dose modifications This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint Clinical and laboratory toxicities
Trial Locations
- Locations (132)
Krankenhaus Der Barmherzigen Brueder
🇦🇹Graz, AT, Austria
Univ. Clinic for Gynaecology and Obstetrics - Medical University of Innsbruck
🇦🇹Innsbruck, AT, Austria
Medizinische Universitat Graz
🇦🇹Graz, Austria
Univ. Klinik Frauenheilkunde AKH
🇦🇹Wien, Austria
Imeldaziekenhuis
🇧🇪Bonheiden, BE, Belgium
AZ Klina
🇧🇪Brasschaat, BE, Belgium
Antwerp University Hospital
🇧🇪Edegem, BE, Belgium
UZ Leuven
🇧🇪Leuven, BE, Belgium
CMSE Clinique et Maternité Sainte-Elisabeth
🇧🇪Namur, BE, Belgium
Az Damiaan
🇧🇪Oostende, BE, Belgium
Scroll for more (122 remaining)Krankenhaus Der Barmherzigen Brueder🇦🇹Graz, AT, Austria