malignant ascites MedDRA version: 14.0 Level: PT Classification code 10025538 Term: Malignant ascites System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Removab 10 microgram
Product Name: catumaxomab (INN)
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: catumaxomab
CAS Number: 509077-98-9
Concentration unit
Sponsors
Fresenius Biotech GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients will be enrolled in this study only if they meet all of the following criteria: • Signed and dated informed consent, • Age: =18 years, • Karnofsky index =60%, • Histological confirmed diagnosis of epithelial cancer, • Patients with malignant ascites requiring therapeutic ascites paracentesis, • Patients where standard therapy is not available or no longer feasible, • Life expectancy >12 weeks, • BMI between 17 and 40kg/m2; prior to calculation of BMI reduce "body weight" by weight of current estimated ascites volume (exploratory value is sufficient) Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 230 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 230
Exclusion criteria
Exclusion criteria: Patients will not be enrolled in this study if they meet any of the following criteria: • Documented acute or chronic infection, • Concomitant treatment with other investigational product, cancer chemo-, or radiotherapy, • In cases of previous exposure to investigational product, cancer, chemo- or radiotherapy (except for local radiation therapy for bone marrow metastasis) patients must be excluded if not sufficiently recovered from previous treatment (toxicity present) based on adequate laboratory values and general status according to other in/exclusion criteria (i.e. this might be less than 1 or 2 weeks after a weekly or bi-weekly scheduled previous therapy regimen). Patients must not have been exposed to nitrosoureas or mitomycin C within 6 weeks prior to the first infusion of catumaxomab. • Previous treatment with entirely murine monoclonal antibodies • Known or suspected hypersensitivity to catumaxomab or similar antibodies, • Long-lasting steroid treatment (= 7 days), Patients should only be included after stepwise discontinuation and free of steroids for a minimum of 5 days • Inadequate respiratory function, including symptomatic pleural effusion, • Inadequate renal function (creatinine >1.5 x upper limit of normal [ULN], • Inadequate hepatic function (aspartate aminotransferase, (AST), alanine aminotransferase (ALT) >5x ULN; bilirubin >1.5ULN) • Platelets 2 x ULN • Hemoglobin II), • Liver metastases with volume >70% of liver metastasized tissue, • Known portal vein obstruction, • Known brain metastases, • Pregnant (as evidenced by positive pregnancy test at screening), or nursing women or women of childbearing potential and men who are not using an effective contraceptive method during the study and at least 3 months after the last infusion, • Unable or unwilling to comply fully with the protocol, • Patients with any other severe disease that would render a participation in the study an undue risk according to judgment of investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to compare the 3 hour i.p. infusion of catumaxomab with prednisolone to catumaxomab without prednisolone by demonstrating superiority for safety and non inferiority for efficacy.;Timepoint(s) of evaluation of this end point: Primary endpoint safety: Up to and including safety visit. Primary efficacy endpoint: first need for therapeutic ascites puncture or death, whichever occurs first;Secondary Objective: The secondary objectives of the study are to determine additional efficacy, additional safety, Quality of Life, human anti mouse antibodies (HAMAs), and ascites-related symptom score following a 3 hour i.p. infusion of catumaxomab with and without prednisolone. Immunomonitoring and pharmacokinetics (PK) will be assessed at selected sites.;Primary end point(s): The primary endpoint consists of 2 parts analyzed in a hierarchical manner: 1. Safety: Composite safety score of 3 hours i.p. infusion of catumaxomab with and without prednisolone. The composite safety score is calculated from the frequency and intensity of the main known adverse events (AEs) caused by catumaxomab: fever, nausea, vomiting, and abdominal pain. The CTC-grade of these AEs will be summarized using an AE-score. The composite safety score will be compared between the 2 treatment groups. 2. Efficacy A co-primary endpoint is puncture-free survival (PuFS) defined as the time from clock start to first need for therapeutic ascites puncture or death, whichever occurs first. The clock starts after the last infusion of catumaxomab. In order to objectify the need for a therapeutic puncture, an ascites puncture will only be performed if there is a medical need according to predefined criteria. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy endpoints: • Time to next ascites puncture, • Number of ascites punctures until end of life time, • Overall survival, • Anti-cancer treatment (Type, No. of treatments). Safety endpoints: • Incidence and severity of all AEs, No. of patients with AE • Incidence of cytokine release related symptoms • Hospitalization • Changes in clinically relevant laboratory values hematology, clinical chemistry, coagulation, and urinalysis), • Physical examination, • Vital signs. Additional parameters: • EpCAM evaluation (retrospective) of ascites cells at screening, • Quality of Life (EQ-5D), • Ascites-related symptoms (FACIT-AI), • Human anti-mouse antibody (HAMA) • PK (at selected sites only), • Immunomonitoring (at selected sites).;Timepoint(s) of evaluation of this end point: Time to ascites puncture, number of ascites punctures, anti-cancer treatment and OS until death or 6 months after the last patient is randomized. Incidence and severity AEs, Number of patients with AE, Incidence of cytokine release related symptoms, Changes in clinically relevant laboratory values, physical examination and vital signs until Safety Visit; Hospitalization until End of Study: EpCam at Screening or day 0 (before first treatment); QOL + Ascites related symptoms until End of Study; Human anti-mouse antibody (HAMA) during treatment until first puncture after end of treatment; PK before and during treatment period, until day 28 after last infusion and on day of first puncture after treatment; Immunomonitoring until Safety Visit. | — |
Countries
Austria, Belgium, France, Germany, Italy, Netherlands, Poland, Sweden, Ukraine, United Kingdom
Contacts
Public ContactMedical Information
Fresenius Biotech GmbH
Outcome results
None listed