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

Cancer Clinical Trial

— CASIMAS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00822809
• Other study ID #: IP-CAT-AC-03
• Status: Completed
• Phase: Phase 3
• First received: December 23, 2008
• Last updated: October 2, 2012
• Start date: December 2008
• Est. completion date: April 2011

Study information

• Verified date: August 2012
• Source: Neovii Biotech
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 230
• Est. completion date: April 2011
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Key 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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ascites
• Cancer
• Carcinoma
• Malignant Ascites
• Neoplasms

Intervention

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
• Prednisolone
25 mg premedication

Locations

Country	Name	City	State
France	Study Site	Several
Germany	Study site	Several
Italy	Study Site	Several
Spain	Study Site	Several

Sponsors (1)

Lead Sponsor	Collaborator
Neovii Biotech

Countries where clinical trial is conducted

France,  Germany,  Italy,  Spain, 

References & Publications (3)

Burges A, Wimberger P, Kümper C, Gorbounova V, Sommer H, Schmalfeldt B, Pfisterer J, Lichinitser M, Makhson A, Moiseyenko V, Lahr A, Schulze E, Jäger M, Ströhlein MA, Heiss MM, Gottwald T, Lindhofer H, Kimmig R. Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM x anti-CD3 antibody: a phase I/II study. Clin Cancer Res. 2007 Jul 1;13(13):3899-905. — View Citation

Lordick F, Ott K, Weitz J, Jäger D. The evolving role of catumaxomab in gastric cancer. Expert Opin Biol Ther. 2008 Sep;8(9):1407-15. doi: 10.1517/14712598.8.9.1407 . Review. — View Citation

Shen J, Zhu Z. Catumaxomab, a rat/murine hybrid trifunctional bispecific monoclonal antibody for the treatment of cancer. Curr Opin Mol Ther. 2008 Jun;10(3):273-84. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Influence of prednisolone on the safety of 3 hours i.p. infusion of catumaxomab measured by a composite safety score		6 months	Yes
Primary	Puncture-free survival defined as the time from clock start to first need for therapeutic ascites puncture or death, whichever occurs first.		6 months	No
Secondary	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	Yes
Secondary	Time to next ascites puncture, number of ascites punctures until end of lifetime, overall survival, anti-cancer treatment		6 months	No
Secondary	immune monitoring		6 months	Yes