Cancer, Carcinoma, Malignant Ascites, Neoplasms
Conditions
Keywords
Cancer, Neoplasms, Carcinoma, Malignant Ascites, Drug therapy, Antineoplastic Protocols, Immunotherapy, Phase III, trifunctional antibody, monoclonal antibody, EpCAM
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.
Interventions
DRUGPrednisolone
25 mg premedication
DRUGCatumaxomab
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
Sponsors
Neovii Biotech
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
France, Germany, Italy, Spain
Outcome results
None listed