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

Sponsor

Neovii Biotech (Industry)

Overall Status

Completed

CT.gov ID

NCT00822809

Collaborator

(none)

230

Enrollment

Locations

Arms

Duration (Months)

57.5

Patients Per Site

2.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cancer Neoplasms Carcinoma Malignant Ascites	Drug: Catumaxomab Drug: Prednisolone	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

230 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2008

Actual Primary Completion Date :

Nov 1, 2010

Actual Study Completion Date :

Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A 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 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 Drug: Prednisolone 25 mg premedication
Other: B Catumaxomab will be administered in a dosage identical to Arm A but without the prednisolone premedication.	Drug: Catumaxomab 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

Arm

Intervention/Treatment

Experimental: A

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

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

Drug: Prednisolone

25 mg premedication

Other: B

Catumaxomab will be administered in a dosage identical to Arm A but without the prednisolone premedication.

Drug: Catumaxomab

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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