Serious epithelial ovarian cancer including primary peritoneal and fallopian tube malignancies MedDRA version: 20.0 Level: PT Classification code 10033160 Term: Ovarian epithelial cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Eisai Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Female subjects who are at least 18 years of age at the time of informed consent 2.CA125 =3 x ULN (105 U/mL) confirmed within 2 weeks of randomization using a centralized laboratory assay 3.A histologically confirmed diagnosis of high-grade serous epithelial ovarian cancer including primary peritoneal and fallopian tube malignancies; all other histologies, including mixed histology, are excluded 4.Have been treated with debulking surgery and a first-line platinum-based chemotherapy regimen 5.Maintenance therapy during the first platinum-free interval is allowed; however, the last dose must have been at least 21 days prior to Randomization. 6.Must be in a first relapse and have evaluable disease by CT or MRI scan, according to RECIST 1.1 (subjects with measurable disease per RECIST 1.1 or radiographically visible and evaluable disease). Subjects with only ascites or pleural effusion are excluded. See Appendix 4. 7.Must have relapsed radiographically within =6 months and =36 months of completion of first-line platinum chemotherapy. 8.Must be a candidate for treatment with either carboplatin plus paclitaxel or carboplatin plus PLD with no medical contraindications present as outlined in the product labels for the selected regimen to be used in this study. 9.Have a life expectancy of at least 6 months, as estimated by the investigator 10.Other significant medical conditions must be well-controlled and stable in the opinion of the investigator for at least 30 days prior to Randomization 11.Have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0 2 12.Subjects being enrolled to receive paclitaxel plus carboplatin treatment must have neuropathic function (sensory and motor) = Grade 2 according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) v4.03 (National Cancer Institute, 2010) 13.Laboratory results within the 2 weeks prior to Randomization must be as follows: -Absolute neutrophil count (ANC) =1,500 cells/mm3 -Platelet count =100,000 cells/mm3 -Hemoglobin =9 g/dL -Creatinine <1.5xULN (CTCAE Grade 1) -Bilirubin <1.5xULN (CTCAE Grade 1) -Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ?3xULN (CTCAE Grade 1) -Alkaline Phosphatase <2.5xULN (CTCAE Grade 1) -Baseline albumin = Lower Limit of Normal 14.Subjects of childbearing potential must be surgically sterile or consent to use a medically acceptable method of contraception throughout the study period. All females will be considered to be of childbearing potential unless they are postmenopausal (eg, amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing). If a patient of childbearing potential is neither surgically sterile nor postmenopausal, a highly-effective contraceptive method (ie, a method that can achieve a failure rate of less than 1% per year when used consistently and correctly) must start either prior to or at Screening and continue throughout the entire study period and for 6 months after the last dose of Test Article is administered. Pregnant and/or lactating females are excluded 15.Subject must provide written informed consent and be willing and able to comply with all aspects of the protocol Are the trial subjects under 18? no Number of subjects for this age range: F.1
Exclusion criteria
Exclusion criteria: 1.Known central nervous system (CNS) tumor involvement 2.Evidence of other active invasive malignancy requiring treatment other than surgery in the past 3 years 3.Clinically significant heart disease (eg, congestive heart failure of New York Heart Association Class 3 or 4, angina not well controlled by medication, or myocardial infarction within 6 months) 4.Electrocardiogram (ECG) demonstrating clinically significant arrhythmias that are not adequately medically managed (Note: subjects with chronic atrial arrhythmia, ie, atrial fibrillation or paroxysmal supraventricular tachycardia [SVT], are eligible) 5.Active serious systemic disease, including active bacterial or fungal infection 6.Active viral hepatitis or active human immunodeficiency virus (HIV) infection. Asymptomatic positive serology is not exclusionary. 7.Other concurrent immunotherapy (eg, immunosuppressants or chronic use of systemic corticosteroids, with the exception that low-dose corticosteroids [50 mg/day prednisone or equivalent corticosteroid] are allowed; these should be discussed with the Medical Monitor) 8.Known allergic reaction to a prior monoclonal antibody therapy or have any documented Anti-Drug Antibody (ADA) response; additionally known allergic reaction to the concomitant chemotherapies selected by the investigator for planned treatment in this study unless desensitization is planned. 9.Previous treatment with farletuzumab or other folate receptor targeting agents 10.Previous treatment with cancer vaccine therapy 11.For subjects being enrolled to receive carboplatin plus PLD, prior treatment with anthracyclines or anthracenodiones 12.Breast-feeding, pregnant, or likely to become pregnant during the study 13.Any medical or other condition that, in the opinion of the investigator, would preclude the subject’s participation in a clinical study including medical contraindications as outlined in the product labels for the chemotherapies selected by the investigator for planned treatment in this study 14. Patients who have had secondary debulking surgery or any second line therapy 15.Currently enrolled in another clinical study or used any investigational drug or device within 30 days (or 5 x half-life for investigational drugs where the half-life is known) preceding informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that farletuzumab has superior efficacy compared with placebo in improving PFS, as determined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 (Eisenhauer, et al., 2009), when added to the standard chemotherapy regimens of carboplatin plus paclitaxel or carboplatin plus PLD, in subjects with platinum-sensitive ovarian cancer in first relapse who have a CA125 = 3xULN (105 U/mL) at study entry.;Secondary Objective: •To assess the effect of farletuzumab on overall survival (OS) in this population •To assess the effect of farletuzumab in prolonging second platinum-free interval longer than first platinum-free interval •To assess the effect of farletuzumab on best objective response (OR) rate, time to response (TTR) and duration of response (DR) by RECIST 1.1 criteria •To assess the safety and tolerability of farletuzumab •To assess the pharmacokinetics and exposure-response relationships between farletuzumab and PFS and OS ;Primary end point(s): The primary efficacy endpoint for this study is PFS based on the investigators’ radiographic assessments utilizing RECIST 1.1 criteria. If progression or death is not observed for a subject, the PFS time will be censored at the date of last tumor assessment without evidence of progression prior to the date of initiation of further anticancer treatment or the cut-off date, whichever is earliest. Detailed censoring rules will be outlined in the SAP.;Timepoint(s) of evaluation of this end point: PFS is defined as the time (in months) from the date of randomization to the date of the first observation of progression (RECIST 1.1), or date of death, whatever the cause. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): OS: Defined as the time from the date of randomization to the date of death, due to all causes. If death is not observed for a subject, the OS time will be censored at the last date known to be alive or the cut-off date, whichever is earliest. Length of First vs Second Platinum-Free Interval: Length of first platinum-free interval is defined as the period of time (in months) from the date of completion of previous platinum based chemotherapy until date of first relapse (ie, first observation of progression), as recorded on the eCRF. The date of first relapse is the progression date based on a radiographic assessment. Similarly, length of second platinum-free interval is defined as the period of time (in months) from the date of completion of platinum based chemotherapy (last dosing date) during the study until the date of progression based on the investigator’s radiographic assessment (RECIST 1.1). Tumor Response (OR, TTR, DR per RECIST 1.1): OR is defined as either a CR or a PR using RECIST 1.1 criteria. Tumor assessments performed up to the initiation of further anticancer treatment will be considered. TTR is defined as the time (in months) from the date of randomization to the date of first observation of response (PR or CR). DR is defined as the time (in months) from the date of first observation of response (PR or CR) to the date of the first observation of progression based on the investigator’s radiographic assessment (RECIST 1.1), or date of death, whatever the cause.;Timepoint(s) of evaluation of this end point: OS: Defined as the time from the date of randomization to the date of death, due to all causes. Length of first platinum-free interval is defined as the period of time (in months) from the date of completion of previous platinum based chemotherapy until date of first relapse. Tumor Response: OR is defined as either a Complete response or a Partial response using RECIST 1.1 criteria. Time To Response is defined as the ti | — |
Countries
Belgium, Germany, Italy, Japan, Spain, United Kingdom, United States
Contacts
Public ContactMedical Information
Eisai Europe Ltd
Outcome results
None listed