Clinical trial NCT00822809: CASIMAS: Catumaxomab Safety Phase IIIb Study With Intraperitoneal Infusion in Patients With Malignant Ascites Due to Epithelial Cancers
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cancer
Neoplasms
Carcinoma
Malignant Ascites
Keywords: Cancer
Neoplasms
Carcinoma
Malignant Ascites
Drug therapy
Antineoplastic Protocols
Immunotherapy
Phase III
trifunctional antibody
monoclonal antibody
EpCAM
Lead sponsor: Neovii Biotech
Sponsor class: INDUSTRY
First posted: 2009-01-14
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Influence of prednisolone on the safety of 3 hours i.p. infusion of catumaxomab measured by a composite safety score
timeFrame: 6 months
measure: Puncture-free survival defined as the time from clock start to first need for therapeutic ascites puncture or death, whichever occurs first.
timeFrame: 6 months
Secondary outcomes:
measure: Safety measured by • Incidence of all AEs, • Changes in clinically relevant laboratory values (hematology, clinical chemistry, coagulation, and urinalysis), • Physical examination, • Vital signs.
timeFrame: 6 months
measure: Time to next ascites puncture, number of ascites punctures until end of lifetime, overall survival, anti-cancer treatment
timeFrame: 6 months
measure: immune monitoring
timeFrame: 6 months
Other outcomes:
Locations:
city: Several
country: France
facility: Study Site
city: Several
country: Germany
facility: Study site
city: Several
country: Italy
facility: Study Site
city: Several
country: Spain
facility: Study Site
Study officials:
affiliation: Med. Klinik III, Städtisches Klinikum Braunschweig gGmbH, Celler STr. 38, 38114 Braunschweig
name: Florian Lordick, PD Dr. med.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lordick F, Ott K, Weitz J, Jager 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.
citation: Burges A, Wimberger P, Kumper C, Gorbounova V, Sommer H, Schmalfeldt B, Pfisterer J, Lichinitser M, Makhson A, Moiseyenko V, Lahr A, Schulze E, Jager M, Strohlein 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. doi: 10.1158/1078-0432.CCR-06-2769.
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.
citation: Fossati M, Buzzonetti A, Monego G, Catzola V, Scambia G, Fattorossi A, Battaglia A. Immunological changes in the ascites of cancer patients after intraperitoneal administration of the bispecific antibody catumaxomab (anti-EpCAMxanti-CD3). Gynecol Oncol. 2015 Aug;138(2):343-51. doi: 10.1016/j.ygyno.2015.06.003. Epub 2015 Jun 3.