Ovarian Cancer
Conditions
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.
Interventions
DRUGCarboplatin
Carboplatin AUC 5
DRUGPegylated Lipoxomal Doxorubicin (PLD)
PLD 30 mg/m² i.v.
DRUGTrabectedin
trabectedin 1.1 mg/m2 3-hour i.v. infusion on Day 1 every 3 weeks. The use of central venous access is strongly recommended.
Sponsors
PharmaMar
Averion International Corporation
Mario Negri Institute for Pharmacological Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Female, aged ≥ 18 years 2. Histologically and/or cytologically proven epithelial ovarian, epithelial fallopian tube cancer or primary peritoneal cancer 3. 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 4. 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. 5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2 6. Estimated life expectancy ≥ 12 weeks 7. Patients must be accessible for treatment and follow-up 8. Adequate organ function within 14 days prior to first cycle as evidenced 9. Patients must be able to receive dexamethasone or its equivalent, which is required if randomly assigned to treatment with trabectedin plus PLD 10. Informed consent of the patient
Exclusion criteria
1. Non epithelial ovarian or mixed epithelial/non epithelial tumors (e.g., Mullerian tumors) 2. 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 3. Bowel obstruction, sub-occlusive disease or the presence of symptomatic brain metastases 4. Pre-existing grade \> 1 motor or sensory neuropathy according to the National Cancer Institute Common Toxicity Criteria Adverse Event (NCI-CTCAE) version 4.0 5. 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 6. History of liver disease 7. 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 8. 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) 9. Prior exposure to trabectedin 10. Prior resistance to anthracyclines or PLD defined as a progression during anthracycline-based chemotherapy or a recurrence within 6 months from its ending 11. Prior severe PLD related toxicity 12. Prior exposure to cumulative doses of doxorubicin \>400mg/m2 or epirubicin \>720mg/m2 13. Treatment with any investigational product within 30 days prior to inclusion in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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. |
| 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. |
| 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 |
| 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 |
| 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). |
| 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. |
| 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. |
| 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 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 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 |
| 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 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 |
Countries
Austria, Belgium, Denmark, Finland, Germany, Italy, Netherlands, Norway, Spain, Switzerland, United Kingdom
Outcome results
None listed