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
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CATUMAXOMAB
CAS Number: 509077-98-9
Concentration unit: µg mi
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: • Patients capable of understanding the purposes and risks of the study, who are willing and able to participate in the study and from whom written and dated informed consent to participate in the study has been obtained • Patients who have completed 4 infusions of catumaxomab in the CASIMAS study. • Age: = 18 years • Karnofsky index = 60% • Patients with malignant ascites requiring their first therapeutic ascites paracentesis after at least 60 days following last catumaxomab infusion in the CASIMAS study. • Patients where standard therapy is either not available or no longer feasible • Body mass index (BMI) between 17 and 40 kg/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 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
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 investigational products other than catumaxomab, cancer, chemo-, or radiotherapy • In cases of previous exposure to investigational product other than catumaxomab, 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. exclusion if 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 other than catumaxomab • Known or suspected hypersensitivity to catumaxomab or similar antibodies • Inadequate respiratory function, including symptomatic pleural effusion, distant metastases other than peritoneal carcinomatosis that lead to significant and/or life threatening respiratory distress and dyspnea at rest due to complications of advanced malignancy or other disease, or patients requiring supportive oxygen therapy • Inadequate renal function (creatinine > 1.5 x upper limit of normal [ULN] or GFR (Glomerular filtration rate) 5 x ULN; alanine aminotransferase [ALT] > 5 x ULN; bilirubin > 1.5 x ULN) • Platelets 2 x ULN • Hemoglobin II) • Liver metastases with volume > 70% of liver metastasized tissue • Known portal vein obstruction • Known brain metastases • Unable or unwilling to comply fully with the protocol • Patients with medical or psychological conditions, which the investigator believes would preclude compliance with the study requirements • Pregnant women, nursing mothers, lactating women, and men or women of child bearing potential who are unwilling to use reliable contraception (hormonal birth control methods including oral contraceptives and contraceptive implants or a barrier method of contraception such as male or female condom, diaphragm, cervical cap plus a spermicide). Effective contraception must be used for the duration of the study and for 6 weeks following completion of the study • Patients with any other severe disease that would render a participation in the study an undue risk according to judgment of investigator. • Patients put into an institution by the authorities of judicial court.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to evaluate the safety of a second 3 hour i.p. infusion cycle, consisting of four ascending dosages of catumaxomab after completing four i.p. infusions in the CASIMAS study, in patients with malignant ascites due to carcinoma requiring their first therapeutic puncture.;Secondary Objective: The secondary objectives of the study are to determine additional safety parameters, efficacy, quality of life, ascites-related symptom score, catheter handling, as well as the pharmacokinetic and pharmacodynamics of a second i.p. infusion cycle with catumaxomab.;Primary end point(s): The primary endpoint is the proportion of patients who are able to receive a second cycle of at least 3 i.p. infusions of catumaxomab.;Timepoint(s) of evaluation of this end point: Primary endpoint: up to and including i.p. infusion 3 at Day 7 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety endpoints: • Composite safety score of 3 hours i.p. infusion of catumaxomab, composed of the main known adverse events (AEs) caused by catumaxomab: fever, nausea, vomiting, and abdominal pain. The score after the first treatment cycle in the CASIMAS study will be compared intra-individually with the score after the second treatment cycle in Study IP-CAT-AC-04 for both treatment groups • The aggregated safety profile in Study IP CAT AC-04 will be compared with the aggregated safety profile of the non prednisolone arm in the CASIMAS study. Analyses will include: o incidence and severity of AEs o number of patients with AEs o incidence of cytokine release related symptoms o hospitalization (frequency and duration) o changes in clinically relevant laboratory values (hematology, clinical chemistry, coagulation, and urinalysis) o physical examination o vital signs o correlation between composite safety score and human anti-mouse antibody (HAMA) development during the second treatment cycle. Efficacy endpoints: • Puncture-free survival • Time to next therapeutic ascites puncture • Number of ascites punctures • Overall survival Additional parameters: • Anti-cancer treatment (type, no. of treatments) • Immunomonitoring (tumor cell count, anti-EpCAM and anti HER2/neu levels, absolute immune cell count in peripheral blood) • Quality of Life (standardized 5-dimensional test for health outcome measurements of the EuroQOL group [EQ-5D]) • Ascites-related symptoms (Functional Assessment of Chronic Illness Therapy - Ascites Index, [FACIT-AI]) • Handling of catheter • HAMA development during the first treatment cycle in the CASIMAS study will be compared to HAMA development during the second treatment cycle in Study IP CAT AC 04 • Pharmacokinetics and anti-drug antibodies (ADAs). Catumaxomab concentrations in plasma and ascites will be compared to respective data of the CASIMAS study. ;Timepoint(s) of evaluation | — |
Countries
Belgium, France, Germany, Italy, Spain, Sweden
Contacts
Public ContactMedical Information
Fresenius Biotech GmbH
Outcome results
None listed