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

Phase 3

Completed

• Conditions: Cancer; Neoplasms; Carcinoma; Malignant Ascites
• Interventions: Drug: Catumaxomab; Drug: Prednisolone

• Registration Number: NCT00822809
• Lead Sponsor: Neovii Biotech

Brief Summary

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

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.

Study Timeline

• Study Start: 2008-12
• Study First Submitted: 2008-12-23
• Study First Submitted QC: 2009-01-13
• Study First Posted: 2009-01-14
• Primary Completion: 2010-11
• Study Completion: 2011-04
• Status Verified: 2012-08
• Last Update Submitted: 2012-10-02
• Last Update Posted: 2012-10-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 230

Inclusion Criteria

1. Patients with malignant ascites requiring therapeutic ascites puncture
2. Histological confirmed diagnosis of epithelial cancer
3. Patients where standard therapy is not available or no longer feasible
4. Karnofsky index ≥60 %
5. Life expectancy >12 weeks

Key

Exclusion Criteria

1. Concomitant treatment with other investigational product, chemo-, or radiotherapy
2. Recent exposure to an investigational product
3. Known or suspected hypersensitivity to catumaxomab or similar antibodies
4. Inadequate respiratory, renal or hepatic function
5. Inadequate blood count (platelets, neutrophils)
6. Required entirely parenteral nutrition
7. Patients with ileus or subileus within the last 30 days
8. Liver metastases with volume >70 % of liver tissue
9. Known portal vein obstruction
10. Known Brain metastases
11. Acute or chronic infection
12. Not sufficiently recovered from previous treatment (toxicity present) based on laboratory values and general status
13. Albumin lower than 3 g/dL or total protein < 6g/dL

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
B	Catumaxomab	Catumaxomab will be administered in a dosage identical to Arm A but without the prednisolone premedication.
A	Prednisolone	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.
A	Catumaxomab	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
immune monitoring	6 months
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

Trial Locations

Locations (2)

Study site; 🇩🇪 Several, Germany

Study Site; 🇪🇸 Several, Spain