Malignant ascites represents a severe clinical problem for physicians and patients being confronted with this common symptom of advanced-stage gastrointestinal cancer. Unfortunately, there is no standardized and evidence-based treatment for malignant ascites and therapies which are commonly being used are only temporarily effective. Newer modes of therapy, such as the application of the tri-functional antibody catumaxomab, are associated with significant side effects and are limited to patients in stages of good overall performance. Therefore, there is still an urgent need for more effective, longer-lasting, and less toxic modes of treatment for peritoneal effusions caused by gastrointestinal cancers. Preclinical data strongly suggest that bevacizumab might be a very effective agent for the treatment of malignant ascites, which is in large part caused by the hyperpermeability-promoting factor VEGF. Emerging clinical results from cancer patients with malignant ascites treated with bevacizumab add further support to this idea. Bevacizumab has been tested in a variety of large clinical trials, has a good toxicity profile, and is effective in a number of human cancers underlying malignant ascites. In the present study, Bevacizumab will be administered as an intraperitoneal infusion at an absolute standardized dosage of 400 mg. This dosage was chosen because it is comparable to the approved standard dosage for intravenous administration which was also used in both studies reporting the successful and safe intraperitoneal administration of Bevacizumab to patients with malignant ascites. Finally, a standardized dosage seems more practical in the particular patient population treated in this study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
53
Patients will receive paracentesis as needed for symptom con¬trol. In addition, patients will receive up to 4 intraperitoneal administrations of 400 mg Bevacizumabafter paracentesis has been performed. During the 8-week treatment period, a minimum interval of 14 days will be kept between applications of the study medication.
Patients will receive paracentesis as needed for symptom con¬trol. In addition, patients will receive up to 4 intraperitoneal administrations of Placebo after paracentesis has been performed. During the 8-week treatment period, a minimum interval of 14 days will be kept between applications of the study medication.
Klinikum Ludwigsburg, Klinik für Innere Medizin, Gastroenterologie, Hämato-Onkologie, Diabetologie
Ludwigsburg, Baden-Wurttemberg, Germany
Onkologische Schwerpunktpraxis
Wendlingen, Baden-Wurttemberg, Germany
Klinikum Deggendorf, Medizinische Klinik II
Deggendorf, Bavaria, Germany
Ernst von Bergmann Klinikum, Zentrum für Hämatologie/Onkologie/Strahlenheilkunde
Potsdam, Brandenburg, Germany
Universitätsklinikum Hamburg - Eppendorf, Onkologisches Zentrum
Hamburg, Free and Hanseatic City of Hamburg, Germany
paracentesis-free survival (ParFS)
The first primary endpoint will consist of paracentesis-free survival (ParFS) which will be calculated as the time period between the initial puncture after randomization to the first subsequent paracentesis or other symptomatic treatments for ascites with the exception of diuretics or until death (whichever occurs first)
Time frame: one year
Best Response (BR)
Best Response representing the longest period of time from one paracentesis until next paracentesis within the treatment period or, if longer, from the last paracentesis performed within the treatment period until first subsequent symptomatic treatment for ascites with the exception of diuretics (before end of the standard 4 week follow-up) or, if longer, from the last paracentesis performed within the treatment period until death (before end of the standard 4 week follow-up) or, if longer, from the last paracentesis performed within the treatment period until 4 week follow-up
Time frame: 12 weeks from 1st application
Volume of ascites
Volume of ascites drained by routine paracentesis (ascites volume minus lavage volumes, if applicable)
Time frame: 12 weeks
Quality of life
Quality of life as assessed by standardized questionnaires
Time frame: 12 weeks
Changes in ECOG performance status
Calculation: 12 weeks minus baseline
Time frame: baseline and 12 weeks
Pharmacokinetics of Bevacizumab and VEGF concentrations
Time frame: 12 weeks
Proportions of patients with adverse events grades 3, 4, or 5.
Time frame: 12 weeks
Proportions of patients with adverse events of special interest
any grade of gastrointestinal perforation, gastrointestinal fistulas or other internal fistulas, wound-healing disturbances, hemorrhagic events and arterial thrombo-embolic events.
Time frame: 12 weeks
All adverse events
Time frame: 12 weeks
Changes in laboratory values and vital signs.
Calculation: Value from later timepoints minus baseline value
Time frame: baseline, every two weeks up to week 12
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
MVZ für Innere Medizin in Hamburg-Eppendorf
Hamburg, Free and Hanseatic City of Hamburg, Germany
Klinikum der J.W. Goethe-Univerisität Frankfurt, Klinik für Allgemein- und Viszeralchirurgie
Frankfurt am Main, Hesse, Germany
Klinikum Wetzlar-Braunfels, Medizinische Klinik II
Wetzlar, Hesse, Germany
Klinikum Region Hannover GmbH, Krankenhaus Siloah, Med. Klinik III (Hämatologie & Onkologie)
Hanover, Lower Saxony, Germany
Onkologische Schwerpunktpraxis Hildesheim, Im Medicinum
Hildesheim, Lower Saxony, Germany
...and 16 more locations