Clinical Trial of Lurbinectedin (PM01183) in Platinum Resistant Ovarian Cancer Patients

Study Overview
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Brief Summary
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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).

Official Title
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Phase III Randomized Clinical Trial of Lurbinectedin (PM01183) Versus Pegylated Liposomal Doxorubicin or Topotecan in Patients With Platinum-resistant Ovarian Cancer (CORAIL Trial)

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: Lurbinectedin (PM01183)
* Drug: Pegylated liposomal doxorubicin (PLD)
* Drug: Topotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>lurbinectedin (PM01183) | Drug: Lurbinectedin (PM01183)<br> <br> |
| Active Comparator: Arm B<br>pegylated liposomal doxorubicin OR topotecan | Drug: Pegylated liposomal doxorubicin (PLD)<br> <br> Drug: Topotecan<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival by Independent Review Committee | 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. | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival by Investigator's Assessment | 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. | 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 | 
| Overall Survival (OS) | 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). | 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 | 
| Overall Response Rate (ORR) by Independent Review Committee | 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. | At baseline and every eight weeks from randomization until evidence of PD, assessed up to 3 years | 
| Overall Response Rate by Investigator's Assessment | 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. | At baseline and every eight weeks from randomization until evidence of PD, assessed up to 3 years | 
| Duration of Response by Independent Review Committee | 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. | 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 by Investigator's Assessment | 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. | 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 | 
| Best Response According to Tumor Marker Evaluation (CA-125) | 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. | At baseline and every eight weeks from randomization until evidence of PD, up to 3 years |