Refractory Ovarian Cancer with Malignant Ascites MedDRA version: 18.1 Level: PT Classification code 10057529 Term: Ovarian cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Human recombinant MIF antibody
Product Code: BAX69
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: BAX69
Current Sponsor code: BAX69
Concentration unit: mg/ml milligram(s
Sponsors
Baxalta Innovations GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of a signed informed consent 2. Female subjects of non-childbearing potential, 18 years of age and older at the time of screening 3. Anticipated life expectancy >3 months at the time of screening 4. Metastatic ovarian epithelial cancer that is platinum resistant, and has no better option available in the investigator’s opinion 5. Recurrent symptomatic malignant ascites having required 2 paracentesis within a 30-day interval prior to screening 6. ECOG PS of 0 to 2 7. Adequate hematological function, defined as: Platelet count =100,000/µL Prothrombin time (PT) and activated partial thromboplastin time (aPTT) 50 mL/min or eGFR >50 mL/min/1.73 m2 9. Adequate liver function, defined as: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 times ULN for subjects without liver metastases, or =5 times ULN in the presence of liver metastases Bilirubin =2.0 times ULN, unless subject has known Gilbert’s syndrome 10. Adequate venous access 11. Subject is willing and able to comply with the requirements of the protocol 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 21 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 39
Exclusion criteria
Exclusion criteria: 1. Known central nervous system metastases 2. Prior malignancy within the past 3 years, with the exception of curatively treated basal or squamous cell carcinoma of the skin, ductal carcinoma in situ of breast, in situ cervical carcinoma, and superficial bladder cancer 3. Subjects who have an indwelling draining intraperitoneal catheter 4. Residual AEs >Grade 2 from previous treatment 5. Myocardial infarction within 6 months prior to C1D1, and/or prior diagnoses of congestive heart failure (New York Heart Association Class III or IV), unstable angina, unstable cardiac arrhythmia requiring medication; and/or the subject is at risk for polymorphic ventricular tachycardia (eg, hypokalemia, family history or long QT syndrome) 6. Uncontrolled hypertension defined as systolic blood pressure =160 mmHg and/or diastolic blood pressure =100 mmHg confirmed upon repeated measures 7. Left ventricular ejection fraction 450 msec, before C1D1 treatment administration, as determined by screening ECG 9. Received anti-tumor therapy (chemotherapy, radiotherapy, retinoid therapy, or hormonal therapy) within 4 weeks (less than 28 days) prior to C1D1; antibody therapy, molecular targeted therapy within 5 half-lives prior to C1D1. 10. Major surgery within 4 weeks (less than 28 days) prior to C1D1 11. Active joint inflammation or other immune disorder involving joints (osteoarthritis is not exclusionary) 12. Active infection involving IV antibiotics within 2 weeks prior to C1D1 13. Positive serology test for hepatitis B virus (HBV), hepatitis C virus (HCV), or active tuberculosis 14. Positive serology test for human immunodeficiency virus (HIV) type 1 and 2, or known history of other immunodeficiency disease 15. Albumin <3g/dL or total protein <6g/dL (it is not exclusionary if the patient receives albumin prophylactically) 16. Subject has received a live vaccine within 2 weeks (less than 14 days) prior to C1D1 17. Known hypersensitivity to any component of recombinant protein production by Chinese Hamster Ovary cells. 18. Exposure to an investigational product or investigational device in another clinical study within 4 weeks (less than 28 days) prior to screening, or is scheduled to participate in another clinical study involving an investigational product or device during the course of this study 19. Any disorder or disease, or clinically significant abnormality on laboratory or other clinical test(s) (eg, blood tests and ECG), that in medical judgment of the investigator may impede the subject’s participation in the study, pose increased risk to the subject, and/or confound the results of the study 20. Subject is a family member or employee of the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: These objectives are applicable to each Arm separately: 1. To determine the MTD and RP2D of imalumab 2. To compare puncture-free survival (PuFS) to puncture-free interval at baseline;Secondary Objective: These objectives are applicable to each Arm separately: 1. To compare time to first paracentesis post-treatment to puncture-free interval at baseline 2. To compare the ascites volume per unit time before and after imalumab treatment 3. To assess the changes in ascites-related symptoms with imalumab treatment 4. To assess the safety, tolerability, and immunogenicity of imalumab 5. To characterize the PK profile of imalumab in plasma 6. To assess quality of life (QoL) using the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30) with imalumab treatment;Primary end point(s): Safety: Occurrence of DLT. Efficacy: The ratio of PuFS over puncture-free interval at baseline. ;Timepoint(s) of evaluation of this end point: Occurrance of DLT -Time of first drug related AE that occurs during 28 day period after first dose of Imalumab. PuFS is defined as the time from the last dose of BAX69 to the first therapeutic paracentesis after that, or death, whichever occurs first. Puncture-free interval at baseline is calculated as the time between the last 2 therapeutic paracenteses immediately before the first dose of BAX69. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: The ratio of time to first paracentesis post-treatment over puncture-free interval at baseline The change in ascites volume per unit time with treatment. The volume of ascites from the last dose of BAX69 to the first post-treatment therapeutic paracentesis per unit time will be compared to the volume of the last pre-treatment paracentesis per unit time. At each paracentesis, the volume of fluid that can be removed safely (measured by ultrasound-guided paracentesis) to achieve close to dryness should be withdrawn, measured, and documented. The changes in ascites-related symptoms (anorexia, nausea, early satiety, vomiting, abdominal pain, abdominal swelling, dyspnea, fatigue, swollen ankles, and heartburn) at baseline, weekly during the treatment period, and every 2 weeks during the Safety Follow-up period using a four-point Likert scale (none, mild, moderate, and severe) for self-reporting. Safety and Immunogenicity: Occurrence of serious adverse events (SAEs) and/or TEAEs, regardless of causality or relationship to study drug graded using NCI CTCAE v4.03 Occurrence of binding and/or neutralizing anti-BAX69 antibodies following treatment with BAX69 PK: BAX69 plasma PK parameters will be calculated, if estimable, using non compartmental methods and/or population PK modeling (including maximum observed concentration [Cmax], minimum observed concentration [Cmin], area under the concentration vs time curve [AUC], half-life [t1/2], apparent systemic clearance [CL/F], and volume of distribution [Vz/F]) QoL: QoL will be assessed using EORTC QLQ-C30;Timepoint(s) of evaluation of this end point: Efficacy: Time to first paracentesis post-treatment is calculated as the time between the last dose of BAX69 to subsequent first therapeutic paracentesis. At each paracentesis, the volume of fluid that can be removed safely (measured by ultrasound-guided paracentesis) to achieve close to dryness should be withdrawn, measured, | — |
Countries
Hungary, Poland, United Kingdom, United States
Contacts
Public ContactClinical Project Managers
Baxalta Innovations GmbH
Outcome results
None listed