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

Ovarian Cancer Clinical Trial

— CORAIL  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02421588
• Other study ID #: PM1183-C-004-14
• Status: Completed
• Phase: Phase 3
• Start date: May 2015
• Est. completion date: October 12, 2018

Study information

• Verified date: February 2020
• Source: PharmaMar
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 442
• Est. completion date: October 12, 2018
• Est. primary completion date: October 12, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• Lurbinectedin (PM01183)

• Pegylated liposomal doxorubicin (PLD)

• Topotecan

Locations

Country	Name	City	State
United States	1127	Albany	New York
United States	1117	Asheville	North Carolina
United States	1109	Augusta	Georgia
United States	1121	Brick	New Jersey
United States	1101	Charlotte	North Carolina
United States	1125	Charlotte	North Carolina
United States	1106	Charlottesville	Virginia
United States	1107	Columbus	Ohio
United States	1110	Covington	Louisiana
United States	1118	Dayton	Ohio
United States	1108	Durham	North Carolina
United States	1131	Fort Worth	Texas
United States	1102	Greenbrae	California
United States	1115	Greenville	South Carolina
United States	1128	Houston	Texas
United States	1104	Indianapolis	Indiana
United States	1103	La Jolla	California
United States	1116	Los Angeles	California
United States	1120	Los Angeles	California
United States	1129	Nashville	Tennessee
United States	1105	New York	New York
United States	1113	Palo Alto	California
United States	1112	Peoria	Arizona
United States	1119	Pittsburgh	Pennsylvania
United States	1111	San Francisco	California
United States	1122	Santa Maria	California
United States	1124	Scarborough	Maine
United States	1123	West Hills	California

Sponsors (1)

Lead Sponsor	Collaborator
PharmaMar

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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