Clinical Trial of Lurbinectedin (PM01183) in Platinum Resistant Ovarian Cancer Patients
- Conditions
- Ovarian Cancer
- Interventions
- Registration Number
- NCT02421588
- Lead Sponsor
- PharmaMar
- Brief Summary
Multicenter, open-label, randomized, controlled phase III clinical trial to evaluate the activity and safety of PM01183 versus PLD or topotecan as control arm in patients with platinum-resistant ovarian cancer. PM01183 will be explored as single agent in the experimental arm (Arm A) versus PLD or topotecan in the control arm (Arm B).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 442
- Age >/= 18 years
- Confirmed diagnosis of unresectable epithelial ovarian, fallopian tube or primary peritoneal cancer.
- Platinum-resistant disease (PFI: 1-6 months after last platinum-containing chemotherapy).
- Evaluable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 criteria
- No more than three prior systemic chemotherapy regimens
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) (ECOG PS) ≤ 2
- Adequate hematological, renal, metabolic and hepatic function
- Concomitant diseases/conditions: cardiac disease, immunodeficiency, chronic active hepatitis or cirrhosis, uncontrolled infection, bowel obstruction, any other major illness
- Prior treatment with PM01183, trabectedin, or with both PLD and topotecan.
- Requirement of permanent or frequent (i.e., once per week) external drainages within two weeks prior to randomization
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B Pegylated liposomal doxorubicin (PLD) pegylated liposomal doxorubicin OR topotecan Arm B Topotecan pegylated liposomal doxorubicin OR topotecan Arm A Lurbinectedin (PM01183) lurbinectedin (PM01183)
- Primary Outcome Measures
Name Time Method Progression-free Survival by Independent Review Committee Time from the date of randomization to the date of PD, death (of any cause), or last tumor evaluation, whichever came first, assessed up to 3 years The primary endpoint was PFS by IRC assessment, defined as the time from the date of randomization to the date of documented progression per RECIST v.1.1 or death (regardless of the cause of death). If the patient received further antitumor therapy or was lost to follow-up before PD, PFS was censored at the date of last tumor assessment before the date of subsequent antitumor treatment.
- Secondary Outcome Measures
Name Time Method Progression-free Survival by Investigator's Assessment Time from the date of randomization to the date of PD, death (of any cause), or last tumor evaluation, whichever came first, assessed up to 3 years The primary endpoint was PFS by Investigator's Assessment, defined as the time from the date of randomization to the date of documented progression per RECIST v.1.1 or death (regardless of the cause of death). If the patient received further antitumor therapy or was lost to follow-up before PD, PFS was censored at the date of last tumor assessment before the date of subsequent antitumor treatment.
Overall Survival (OS) From the date of randomization to the date of death or last contact, up to 12 months after last patient inclusion, for a maximum of up to 3 years Calculated from the date of randomization to the date of death (death event) or last contact (in this case, survival was censored on that date).
Overall Response Rate (ORR) by Independent Review Committee At baseline and every eight weeks from randomization until evidence of PD, assessed up to 3 years Best antitumor response defined as the best response obtained according to RECIST v.1.1. Tumor assessment were performed at baseline and every 8 weeks from randomization until evidence of PD. Patients who discontinued treatment without PD continued with assessments.
Antitumor activity was assessed using the RECIST v.1.1 by the appropriate method \[computed tomography scan or magnetic resonance imaging\]: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters; Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum; Overall Response (OR)=CR+PR.Overall Response Rate by Investigator's Assessment At baseline and every eight weeks from randomization until evidence of PD, assessed up to 3 years Best antitumor response defined as the best response obtained according to RECIST v.1.1. Tumor assessment were performed at baseline and every 8 weeks from randomization until evidence of PD. Patients who discontinued treatment without PD continued with assessments.
Antitumor activity was assessed using the RECIST v.1.1 by the appropriate method \[computed tomography scan or magnetic resonance imaging\]: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters; Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum; Overall Response (OR)=CR+PR.Duration of Response by Independent Review Committee The time from the date when the response criteria (PR or CR, whichever was reached first) were fulfilled, to the first date when PD, recurrence or death was documented, up to 3 years Duration of response (DR): calculated from the date of first documentation of response per RECIST v.1.1 (CR or PR, whichever came first) to the date of documented PD or death. The censoring rules defined above for PFS were used for duration of response.
Best antitumor response defined as the best response obtained according to RECIST v.1.1. Tumor assessment were performed at baseline and every 8 weeks from randomization until evidence of PD. Patients who discontinued treatment without PD continued with assessments.
Antitumor activity was assessed using the RECIST v.1.1 by the appropriate method \[computed tomography scan or magnetic resonance imaging\]: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)=CR+PR.Duration of Response by Investigator's Assessment The time from the date when the response criteria (PR or CR, whichever was reached first) were fulfilled, to the first date when PD, recurrence or death was documented, up to 3 years Duration of response (DR): calculated from the date of first documentation of response per RECIST v.1.1 (CR or PR, whichever came first) to the date of documented PD or death. The censoring rules defined above for PFS were used for duration of response.
Best antitumor response defined as the best response obtained according to RECIST v.1.1. Tumor assessment were performed at baseline and every 8 weeks from randomization until evidence of PD. Patients who discontinued treatment without PD continued with assessments.
Antitumor activity was assessed using the RECIST v.1.1 by the appropriate method \[computed tomography scan or magnetic resonance imaging\]: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)=CR+PR.Best Response According to Tumor Marker Evaluation (CA-125) At baseline and every eight weeks from randomization until evidence of PD, up to 3 years Best response according to tumor marker evaluation (CA-125): defined as the best response obtained according to GCIG criteria. Tumor marker assessments were performed at baseline and every eight weeks from randomization until evidence of PD. Progression based on serum CA-125 levels was defined on the basis of a progressive serial elevation of serum CA-125 according to:
A. Patients with elevated CA-125 pretreatment and normalization of CA-125 must show evidence of CA-125 greater than, or equal to, 2 times the upper limit of the reference range on 2 occasions at least 1 week apart or B. Patients with elevated CA-125 before treatment, which never normalizes, must show evidence of CA-125 greater than, or equal to, 2 times the nadir value on 2 occasions at least 1 week apart or C. Patients with CA-125 in the reference range before treatment must show evidence of CA-125 greater than, or equal to, 2 times the upper limit of the reference range on 2 occasions at least 1 week apart.
Trial Locations
- Locations (28)
1120
🇺🇸Los Angeles, California, United States
1124
🇺🇸Scarborough, Maine, United States
1118
🇺🇸Dayton, Ohio, United States
1110
🇺🇸Covington, Louisiana, United States
1107
🇺🇸Columbus, Ohio, United States
1115
🇺🇸Greenville, South Carolina, United States
1127
🇺🇸Albany, New York, United States
1121
🇺🇸Brick, New Jersey, United States
1123
🇺🇸West Hills, California, United States
1116
🇺🇸Los Angeles, California, United States
1122
🇺🇸Santa Maria, California, United States
1102
🇺🇸Greenbrae, California, United States
1109
🇺🇸Augusta, Georgia, United States
1103
🇺🇸La Jolla, California, United States
1113
🇺🇸Palo Alto, California, United States
1105
🇺🇸New York, New York, United States
1125
🇺🇸Charlotte, North Carolina, United States
1117
🇺🇸Asheville, North Carolina, United States
1101
🇺🇸Charlotte, North Carolina, United States
1119
🇺🇸Pittsburgh, Pennsylvania, United States
1106
🇺🇸Charlottesville, Virginia, United States
1131
🇺🇸Fort Worth, Texas, United States
1112
🇺🇸Peoria, Arizona, United States
1111
🇺🇸San Francisco, California, United States
1104
🇺🇸Indianapolis, Indiana, United States
1129
🇺🇸Nashville, Tennessee, United States
1108
🇺🇸Durham, North Carolina, United States
1128
🇺🇸Houston, Texas, United States