Bevacizumab as a Palliative Treatment for Patients With Symptomatic Malignant Ascites Due to Advanced-stage Gastrointestinal Cancers

NCT01200121 | Completed Phase 2 DMC

• 1 other identifier: AIO-SUP-0108
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 26

Brief Summary

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.

Conditions

Malignant Ascites; Gastrointestinal Cancers

Keywords

Symptomatic malignant ascites due to advanced-stage gastrointestinal cancers

Outcome Measures

Primary Outcomes (1)

• 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)

  one year

Secondary Outcomes (9)

• Best Response (BR)

  12 weeks from 1st application

• Volume of ascites

  12 weeks

• Quality of life

  12 weeks

• Changes in ECOG performance status

  baseline and 12 weeks

• Pharmacokinetics of Bevacizumab and VEGF concentrations

  12 weeks

Study Arms (2)

Arm A Bevacizumab

EXPERIMENTAL

48 patients randomized into arm A will receive repeated intra¬peritoneal application of Bevacizumab

Drug: Bevacizumab

Arm B Placebo

PLACEBO COMPARATOR

26 patients randomized into arm B will receive repeated intra¬peritoneal application of Placebo

Other: Placebo

Interventions

Bevacizumab DRUG

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.

Also known as: Avastin

Arm A Bevacizumab

Placebo OTHER

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.

Arm B Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>= 18 years
• Written informed consent has been obtained prior to inclu¬sion into the study
• Patient is capable and willing to comply with the study
• Histologically confirmed esophageal, gastric, pancreatic, cholangiocellular, hepatocellular, or colorectal carcinoma
• Cytologically confirmed ascites OR diagnosis of an exsudate (total protein in ascites \> 30 g/l) clinically suggestive for malignant ascites OR morphological diagnosis of peritoneal carcinosis by CT , MRT or ultrasound
• Ascites clinically judged as not responsive to conventional systemic therapies for primary malignancy
• Ascites clinically judged as not responsive to diuretics

You may not qualify if:

• ECOG performance score 0-3
• Life expectancy \> 12 weeks
• Laboratory parameters:
• Hematology
• Neutrophils \> 1,500/µl
• Platelets \> 100,000/µl
• Hemoglobin \>= 9 g/dl or 5.59 mmol/l Hemastasiology
• INR \<= 1.5 x ULN and aPTT \<= 1.5 x ULN within past 7 dClinical chemistry
• Creatinine clearance \> 30 ml/min, serum creatinine \< 2.5 x ULN
• Serum bilirubin \< 3.0 x ULN
• Alkaline phosphatase and transaminases \< 3.0 x ULN (in case of liver metastases \< 7 x ULN)
• Urinalysis:
• Patients with \< 2+ proteinuria on dipstick urinalysis.
• Patients with \>= 2+ proteinuria on dipstick urinalysis, who demonstrate \< 2.0 g of protein/24 h on 24-h urine collection
• Concomitant malignancies other than gastrointestinal cancers (Patients with curatively treated basal and squamous cell carcino¬ma of the skin and / or in-situ carci¬noma of the cervix are eli¬gible).

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead

Study Sites (26)

Klinikum Ludwigsburg, Klinik für Innere Medizin, Gastroenterologie, Hämato-Onkologie, Diabetologie

Ludwigsburg, Baden-Wurttemberg, 71640, Germany

Location

Onkologische Schwerpunktpraxis

Wendlingen, Baden-Wurttemberg, 73240, Germany

Location

Klinikum Deggendorf, Medizinische Klinik II

Deggendorf, Bavaria, 94469, Germany

Location

Ernst von Bergmann Klinikum, Zentrum für Hämatologie/Onkologie/Strahlenheilkunde

Potsdam, Brandenburg, 14467, Germany

Location

Universitätsklinikum Hamburg - Eppendorf, Onkologisches Zentrum

Hamburg, Hamburg, 20246, Germany

Location

MVZ für Innere Medizin in Hamburg-Eppendorf

Hamburg, Hamburg, 20249, Germany

Location

Klinikum der J.W. Goethe-Univerisität Frankfurt, Klinik für Allgemein- und Viszeralchirurgie

Frankfurt am Main, Hesse, 60590, Germany

Location

Klinikum Wetzlar-Braunfels, Medizinische Klinik II

Wetzlar, Hesse, 35578, Germany

Location

Klinikum Region Hannover GmbH, Krankenhaus Siloah, Med. Klinik III (Hämatologie & Onkologie)

Hanover, Lower Saxony, 30449, Germany

Location

Onkologische Schwerpunktpraxis Hildesheim, Im Medicinum

Hildesheim, Lower Saxony, 31135, Germany

Location

Kliniken Essen-Mitte, Klinik f. intern. Onkologie u. Hämatologie

Essen, North Rhine-Westphalia, 45136, Germany

Location

Universitätsklinikum Essen, Klinik für Innere Medizin - Tumorforschung

Essen, North Rhine-Westphalia, 45147, Germany

Location

Klinikum Leverkusen gGmbH, Medizinische Klinik III

Leverkusen, North Rhine-Westphalia, 51375, Germany

Location

Kliniken Maria Hilf GmbH, Krankenhaus St. Franziskus, Hämatologie/Onkologie/Gastroonkologie

Mönchengladbach, North Rhine-Westphalia, 41063, Germany

Location

Prosper-Hospital, Medizinische Klinik I

Recklinghausen, North Rhine-Westphalia, 45659, Germany

Location

Hämatologisch Onkologische Praxis Würselen

Würselen, North Rhine-Westphalia, 52146, Germany

Location

Johannes Gutenberg Universität, Universitätsklinikum, I. Medizinische Klinik und Poliklinik

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Universitätsklinikum Leipzig, Klinik für Gastroenterologie und Rheumatologie

Leipzig, Saxony, 04103, Germany

Location

Internistische Praxis und Tagesklinik

Neustadt (Sachsen), Saxony, 01844, Germany

Location

Universitätslinikum der Martin-Luther Universität Halle-Wittenberg, Klinik für Innere Medizin IV

Halle, Saxony-Anhalt, 06120, Germany

Location

Friedrich-Ebert-Krankenhaus GmbH, Klinik für Hämatologie, Onkologie/Nephrologie

Neumünster, Schleswig-Holstein, 24534, Germany

Location

Vivantes Klinikum Am Urban, Klinik für Innere Medizin

Berlin, State of Berlin, 10967, Germany

Location

VIVANTES Klinikum Neukölln, Onkologisches Zentrum Vivantes Süd

Berlin, State of Berlin, 12351, Germany

Location

Charité (Campus Virchow-Klinikum), Med. Klinik mit Schwerpunkt Hämatologie und Onkologie

Berlin, State of Berlin, 13353, Germany

Location

Vivantes Klinikum Spandau, Klinik für Innere Medizin

Berlin, State of Berlin, 13585, Germany

Location

Medizinisches Versorgungszentrum, Onkologischer Schwerpunkt

Berlin-Zehlendorf, State of Berlin, 14195, Germany

Location

Related Links

• Related Info

MeSH Terms

Conditions

Gastrointestinal Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Karin Jordan, Dr. med.

  Universitätslinikum der Martin-Luther Universität Halle-Wittenberg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2010
• First Posted: September 13, 2010
• Study Start: February 1, 2010
• Primary Completion: August 1, 2014
• Study Completion: December 1, 2014
• Last Updated: April 13, 2015

Record last verified: 2015-04

Locations

DE (26)