Clinical trial NCT00908219: A Study of Bevacizumab to Prevent Malignant Ascites
Official title: A Prospective, Phase II Trial of Intravenous Bevacizumab (Avastin) for the Prevention of Recurrent Malignant Ascites
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Malignant Ascites
Keywords: malignant ascites
bevacizumab
vascular endothelial growth factor (VEGF)
paracentesis
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2009-05-25
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine the effectiveness of using Bevacizumab in the prevention of recurrent malignant ascites.

Ascites is a debilitating and unpleasant complication of several types of cancer. Animal and laboratory studies have shown that tumor cell production and/or increases in the amount of Vascular Endothelial Growth Factor (VEGF) is a major cause of the formation of malignant ascites. Therefore, giving patients with malignant ascites a drug that targets and neutralizes VEGF should prevent the recurrence of malignant ascites following paracentesis (a procedure to remove fluid from the abdominal cavity).

Detailed description: All subjects will be treated with an intravenous infusion of the experimental drug (Bevacizumab 15 mg/kg) every 3 weeks for a total of twelve (12) weeks on study. The primary endpoint will be time to the need for repeat abdominal paracentesis after the start of therapy. Secondary endpoints will include an analysis of the mean number of paracenteses required in each subject over the course of 3 months, determination of the repeat paracentesis response rate (proportion of subjects who have a doubling in baseline time to repeat paracentesis) and an assessment of the effect of treatment on quality of life using a subject questionnaire.

Eligibility criteria: Inclusion Criteria:

* Persistent or symptomatic ascites with positive cytology secondary to any histologically confirmed tumor type not amenable to cytoreductive surgery or additional chemotherapy
* Patients may enroll in this study irrespective of previous therapy including diuretics, surgery, chemotherapy, immunotherapy and radiation therapy
* Must have received a minimum of two paracentesis procedures and a trial of diuretic therapy within 60 days of study entry
* Age Restrictions: 18 years and older
* Life Expectancy: 12 weeks or more
* ECOG Performance Status: 0 -3
* Able and willing to provide informed consent and comply with study and/or follow-up procedures
* Normal organ and marrow function as defined by: Leukocytes \>/= 3,000/mcL; Absolute neutrophil count \>/= 1,500/mcL; Platelets \>/= 100,000/mcL; Total bilirubin within normal institutional limits; AST (SGOT)/ALT(SGPT) \</= 2.5 X institutional upper limit of normal (ULN); Creatinine within normal institutional limits OR Creatinine clearance \>/+ 60 mL/min for patients with creatinine levels above the institutional normal; Serum Potassium within normal institutional limits; Serum Sodium within normal institutional limits

Exclusion Criteria:

* Patients having received Bevacizumab as part of the treatment of their malignancy within 60 days prior to study entry
* Current, recent (within 30 days of the first infusion of this study) or planned administration of chemotherapy (including all routes of administration), immunotherapy, biologic therapy, radiation therapy or any other anti-VEGF therapy (e.g., tyrosine kinase inhibitors)
* Current, recent (within 30 days of the first infusion of this study), or planned participation in any other experimental drug study
* Pregnant women; A serum pregnancy test will be given to females of childbearing potential prior to study enrollment and the participant must agree to use adequate contraception (barrier or hormonal methods) prior to study entry and for the duration of study participation.
* Un-controlled hypertension (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg
* History of hypertensive crisis or hypertensive encephalopathy
* New York Heart Association (NYHA) Grade II or greater congestive heart failure
* History of myocardial infarction, unstable angina, stroke or transient ischemic attack within 6 months prior to study entry
* Known CNS disease, except for treated brain metastasis.
* Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to study entry
* History of hemoptysis (\>/= 1/2 teaspoon of bright red blood per episode) within 1 month prior to study entry
* Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study entry or anticipation of need for major surgical procedure during the course of the study
* Core biopsy or other minor surgical procedure, excluding placement of a vascular access device or paracentesis/thoracentesis, within 7 days prior to study entry
* History of abdominal fistula or gastrointestinal perforation within 6 months prior to study entry
* Any bowel obstruction that has not fully recovered despite medical or surgical intervention prior to study entry
* Evidence of bowel wall thickening outside the site of the known primary malignancy on baseline radiographs
* Serious, non-healing wound, active ulcer, or untreated bone fracture
* Proteinuria as demonstrated by a Urine Protein/Creatinine ration \>/= 1.0 at screening
* Known hypersensitivity to any component of bevacizumab
* Intrathoracic lung carcinoma of squamous cell histology.

Primary outcomes:
measure: To determine the repeat paracentesis response rate defined as a doubling of the patient's baseline time to repeat paracentesis.
timeFrame: 12 weeks after initiation of study treatment
Secondary outcomes:
measure: To assess the time to the need for the first repeat abdominal paracentesis after the start of Bevacizumab therapy as compared with historical control data.
timeFrame: Unspecified - depends upon when subject will need repeat paracentesis
measure: To analyze the mean number of paracentesis procedures required in each patient over the course of three months.
timeFrame: 12 weeks after the initiation of study treatment
measure: To assess the effect of anti-VEGF therapy on quality of life in patients with malignant ascites.
timeFrame: Every three weeks while on-study
Other outcomes:
Locations:
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Ben Taub General Hospital
state: Texas
city: Houston
country: United States
facility: Michael E. DeBakey Veterans Affairs Medical Center
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: Martha P Mims, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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