Phase III Randomized Clinical Trial of Lurbinectedin (PM01183) versus Pegylated Liposomal Doxorubicin or Topotecan in Patients with Platinumresistant Ovarian Cancer (CORAIL Trial)
- Conditions
- Platinum-resistant ovarian cancerMedDRA version: 20.0Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10033130Term: Ovarian cancer NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-005251-39-IT
- Lead Sponsor
- PHARMA MAR, S.A. SOCIEDAD UNIPERSONA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 442
1) Voluntary written informed consent (IC) of the patient obtained before any study-specific procedure.
2) Age = 18 years.
3) Histologically or cytologically confirmed diagnosis of unresectable epithelial ovarian, fallopian tube or primary peritoneal cancer.
4) Platinum-resistant disease (PFI: 1-6 months after last platinumcontaining chemotherapy).
5) Radiologically measurable and/or non-measurable progressive disease according to RECIST v 1.1.
6) No more than three prior systemic chemotherapy regimens. Note: in case that a patient had started a new systemic chemotherapy without disease progression to the prior chemotherapy line (e.g., treatment discontinuations due to toxicity; neoadjuvant followed by adjuvant chemotherapy regimens), these two chemotherapy regimens will
considered as one.
7) ECOG PS = 2.
8) Adequate hematological, renal, metabolic and hepatic function:
a) Hemoglobin = 9 g/dl [patients may have received prior red blood cell (RBC) transfusion]; absolute neutrophil count (ANC) = 2.0 x 109/l, and platelet count = 100 x 109/l.
b) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3.0 x upper limit of normal (ULN).
c) Alkaline phosphatase (AP) < 5.0 x ULN.
d) Total bilirubin = ULN or direct bilirubin = ULN if total bilirubin is > ULN.
e) Albumin = 3.0 g/dl.
f) Calculated creatinine clearance (CrCL) = 30 ml/min (using Cockcroft and Gault's formula).
g) Creatine phosphokinase (CPK) = 2.5 x ULN.
9) At least three weeks since last prior therapy, and grade = 1 from any adverse event (AE) derived from previous treatment (excluding grade =
2 alopecia or peripheral neuropathy) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v. 4).
10) Women of childbearing potential must have pregnancy excluded by appropriate testing before study entry. A medically acceptable method of
contraception must be maintained throughout the treatment period and for at least six months after treatment discontinuation.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 294
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 126
1) Concomitant diseases/conditions:
a) History of cardiac disease: myocardial infarction or
symptomatic/uncontrolled angina within the year prior to enrollment; or congestive heart failure defined as abnormal left ventricular ejection fraction (LVEF) < 50% assessed by multiple-gated acquisition scan (MUGA) or equivalent by ultrasound (US); or symptomatic arrhythmia.
b) Patients with any immunodeficiency, including those known to be infected by human immunodeficiency virus (HIV).
c) Chronic active hepatitis or cirrhosis. For Hepatitis B, this includes positive tests for both Hepatitis B surface antigen and quantitative Hepatitis B polymerase chain reaction (PCR). For Hepatitis C, this includes positive tests for both Hepatitis C antibody and quantitative Hepatitis C PCR.
d) Active uncontrolled infection.
e) Bowel obstruction.
f) Requirement of permanent or frequent (i.e., once per week) external
drainages within two weeks prior to randomization.
g) Limitation of the patient's ability to comply with the treatment or to follow-up the protocol.
h) Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
2) Platinum-refractory or platinum-sensitive disease (PFI <1 or > 6 months).
3) Prior treatment with PM01183, trabectedin, or with both PLD and topotecan.
Note: if 60% of recruitment is reached in one of the control treatment options (i.e., PLD or topotecan), patients could only be eligible if they did
not previously receive the other control treatment option available (the Sponsor will inform the sites, if this occurs).
4) Known brain metastases or leptomeningeal disease involvement.
5) History of another neoplastic disease (except for curatively treated basal cell carcinoma, squamous cell carcinoma of the skin, or properly treated carcinoma in situ of the uterine cervix or breast) within three years prior to randomization.
6) Pregnant or breast feeding women.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine a difference in progression-free-survival (PFS) between<br>lurbinectedin (PM01183) and pegylated liposomal doxorubicin (PLD) or<br>topotecan in platinum-resistant ovarian cancer patients according to the<br>Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1.;Secondary Objective: To evaluate:<br>- Overall survival (OS).<br>- Antitumor activity.<br>- Safety profile.<br>- Patient-reported outcomes (PRO).<br>To characterize the plasma pharmacokinetics (PK) of PM01183 using a<br>sparse sampling scheme in the PM01183 treatment arm (Arm A).<br>Subgroup analyses of the PM01183 arm versus PLD or topotecan.<br>To conduct an exploratory pharmacogenetic and pharmacogenomic<br>(PGx) sub-study.;Primary end point(s): Progression-free survival (PFS);Timepoint(s) of evaluation of this end point: Along the study
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Progression-free survival (PFS)<br>Overall survival (OS)<br>Landmark analyses:<br>PFS at 6 and 12 months by IRC/IA<br>OS at 12 and 24 months<br>Best antitumor response by IRC/IA<br>Duration of response (DR) by IRC/IA<br>Best response according to tumor marker evaluation (CA-125)<br>Treatment safety profile<br>Patient-reported outcomes (PRO):<br>Plasma pharmacokinetics (PK) of PM01183<br>Subgroup analyses: Subgroup analyses of the PM01183 arm versus PLD<br>or topotecan<br>Pharmacogenetics<br>Pharmacogenomics;Timepoint(s) of evaluation of this end point: Along the study