CASIMAS: Catumaxomab Safety Phase IIIb Study With Intraperitoneal Infusion in Patients With Malignant Ascites Due to Epithelial Cancers

Study Overview
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Brief Summary
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This is a randomized phase IIIb study investigating the treatment of malignant ascites due to epithelial cancer (carcinomas) with the trifunctional antibody catumaxomab. In order to make the catumaxomab treatment more convenient for the patient and the hospital praxis the tolerability of 3 hour infusions of catumaxomab with and without premedication of prednisolone is evaluated. A total of 208 patients with malignant ascites due to epithelial cancer will be allocated to two treatment groups in a 1:1 ratio.

Detailed Description
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Safety data of the completed pivotal phase II/III trial, IP-REM-AC-01, in which catumaxomab was administered as 6 hour i.p. infusion showed that most reported AEs were cytokine release-related symptoms such as fever, nausea, and vomiting (based on the pharmacodynamic mode of action of catumaxomab) and abdominal pain. In order to make the catumaxomab treatment more convenient for the patient and the hospital praxis the current trial was designed to determine whether tolerability of the 3 hour infusion of catumaxomab with and without premedication of prednisolone. Prednisolone was chosen as additional premedication with the objective to reduce cytokine release related symptoms which might change with the switch from 6 to 3 h infusion time.

Official Title
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Two-arm, Randomized, Open-label, Phase IIIb Study Investigating the Safety of a 3 Hour i.p. Infusion of Catumaxomab With and Without Prednisolone Premedication in Patients With Malignant Ascites Due to Epithelial Cancer

Conditions
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Cancer, Neoplasms, Carcinoma, Malignant Ascites

Intervention / Treatment
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* Drug: Catumaxomab
* Drug: Prednisolone


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Patients with malignant ascites requiring therapeutic ascites puncture Histological confirmed diagnosis of epithelial cancer Patients where standard therapy is not available or no longer feasible Karnofsky index ≥60 % Life expectancy >12 weeks Key Exclusion Criteria: Concomitant treatment with other investigational product, chemo-, or radiotherapy Recent exposure to an investigational product Known or suspected hypersensitivity to catumaxomab or similar antibodies Inadequate respiratory, renal or hepatic function Inadequate blood count (platelets, neutrophils) Required entirely parenteral nutrition Patients with ileus or subileus within the last 30 days Liver metastases with volume >70 % of liver tissue Known portal vein obstruction Known Brain metastases Acute or chronic infection Not sufficiently recovered from previous treatment (toxicity present) based on laboratory values and general status Albumin lower than 3 g/dL or total protein < 6g/dL

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Patients will receive premedication of 25 mg (i.v.) prednisolone 30 minutes prior start of infusion of catumaxomab. Catumaxomab will be infused i.p. with 3 hour constant rate infusions via an indwelling catheter. | Drug: Catumaxomab<br>* Catumaxomab will be infused 4 times within 11 days as follows: 10 µg on day 0, 20 µg on day 3, 50 µg on day 7, 150 µg on day 10<br>Drug: Prednisolone<br>* 25 mg premedication<br>|
| Other: B<br>Catumaxomab will be administered in a dosage identical to Arm A but without the prednisolone premedication. | Drug: Catumaxomab<br>* Catumaxomab will be infused 4 times within 11 days as follows: 10 µg on day 0, 20 µg on day 3, 50 µg on day 7, 150 µg on day 10<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Influence of prednisolone on the safety of 3 hours i.p. infusion of catumaxomab measured by a composite safety score |  | 6 months | 
| Puncture-free survival defined as the time from clock start to first need for therapeutic ascites puncture or death, whichever occurs first. |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety measured by • Incidence of all AEs, • Changes in clinically relevant laboratory values (hematology, clinical chemistry, coagulation, and urinalysis), • Physical examination, • Vital signs. |  | 6 months | 
| Time to next ascites puncture, number of ascites punctures until end of lifetime, overall survival, anti-cancer treatment |  | 6 months | 
| immune monitoring |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Neoplasms, Carcinoma, Malignant Ascites, Drug therapy, Antineoplastic Protocols, Immunotherapy, Phase III, trifunctional antibody, monoclonal antibody, EpCAM