A Study of Bevacizumab to Prevent Malignant Ascites - Full Text View

Sponsor:	Baylor College of Medicine
Collaborator:	Genentech
Information provided by:	Baylor College of Medicine
ClinicalTrials.gov Identifier:	NCT00908219

Purpose

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).

Condition	Intervention	Phase
Malignant Ascites	Drug: Bevacizumab	Phase II

Study Type:	Interventional
Study Design:	Prevention, Open Label, Single Group Assignment, Efficacy Study
Official Title:	A Prospective, Phase II Trial of Intravenous Bevacizumab (Avastin) for the Prevention of Recurrent Malignant Ascites

Resource links provided by NLM:

Drug Information available for: Bevacizumab

U.S. FDA Resources

Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:

To determine the repeat paracentesis response rate defined as a doubling of the patient's baseline time to repeat paracentesis. [ Time Frame: 12 weeks after initiation of study treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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. [ Time Frame: Unspecified - depends upon when subject will need repeat paracentesis ] [ Designated as safety issue: No ]
To analyze the mean number of paracentesis procedures required in each patient over the course of three months. [ Time Frame: 12 weeks after the initiation of study treatment ] [ Designated as safety issue: No ]
To assess the effect of anti-VEGF therapy on quality of life in patients with malignant ascites. [ Time Frame: Every three weeks while on-study ] [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	July 2009
Estimated Study Completion Date:	September 2010
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Bevacizumab IV: Experimental 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.	Drug: Bevacizumab Bevacizumab is given as an IV infusion of 15 mg/kg every three weeks for 12 weeks.

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00908219

Contacts

Contact: Maria Sanchez, RN	713-798-4075
Contact: Natalie Nichols, LVN	713-798-4797

Locations

United States, Texas
Baylor College of Medicine	Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Martha P Mims, MD, PhD
Sub-Investigator: Brion V Randolph, MD
Ben Taub General Hospital	Recruiting
Houston, Texas, United States, 77030
Sub-Investigator: Gerald Cyprus, MD
Sub-Investigator: Ahmed Eid, MD
Sub-Investigator: Garrett Lynch, MD
Michael E. DeBakey Veterans Affairs Medical Center	Recruiting
Houston, Texas, United States, 77030
Contact: Monique Detiege 713-791-1414
Sub-Investigator: Teresa Hayes, MD, PhD
Sub-Investigator: Yee Lu Tham, MD
Sub-Investigator: Zahida Yasin, MD
Sub-Investigator: Sarvari Yellapragada, MD
Sub-Investigator: Carlos Arce-Lara, MD
Sub-Investigator: Elizabeth Rogg, MD
Sub-Investigator: Paul Zhang, MD

Sponsors and Collaborators

Baylor College of Medicine

Genentech

Investigators

Principal Investigator:

Martha P Mims, MD, PhD

Baylor College of Medicine

More Information

Publications:

Braunwald, et al. Harrison's Principles of Internal Medicine, 15th Ed. (McGraw-Hill 2001) 517

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004 Jun 3;350(23):2335-42.

Smith EM, Jayson GC. The current and future management of malignant ascites. Clin Oncol (R Coll Radiol). 2003 Apr;15(2):59-72. Review.

Xu L, Yoneda J, Herrera C, Wood J, Killion JJ, Fidler IJ. Inhibition of malignant ascites and growth of human ovarian carcinoma by oral administration of a potent inhibitor of the vascular endothelial growth factor receptor tyrosine kinases. Int J Oncol. 2000 Mar;16(3):445-54.

Yukita A, Asano M, Okamoto T, Mizutani S, Suzuki H. Suppression of ascites formation and re-accumulation associated with human ovarian cancer by an anti-VPF monoclonal antibody in vivo. Anticancer Res. 2000 Jan-Feb;20(1A):155-60.

Zebrowski BK, Liu W, Ramirez K, Akagi Y, Mills GB, Ellis LM. Markedly elevated levels of vascular endothelial growth factor in malignant ascites. Ann Surg Oncol. 1999 Jun;6(4):373-8.

Verheul HM, Hoekman K, Jorna AS, Smit EF, Pinedo HM. Targeting vascular endothelial growth factor blockade: ascites and pleural effusion formation. Oncologist. 2000;5 Suppl 1:45-50.

Luo JC, Toyoda M, Shibuya M. Differential inhibition of fluid accumulation and tumor growth in two mouse ascites tumors by an antivascular endothelial growth factor/permeability factor neutralizing antibody. Cancer Res. 1998 Jun 15;58(12):2594-600.

Zebrowski BK, Yano S, Liu W, Shaheen RM, Hicklin DJ, Putnam JB Jr, Ellis LM. Vascular endothelial growth factor levels and induction of permeability in malignant pleural effusions. Clin Cancer Res. 1999 Nov;5(11):3364-8.

Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983 Feb 25;219(4587):983-5.

Numnum TM, Rocconi RP, Whitworth J, Barnes MN. The use of bevacizumab to palliate symptomatic ascites in patients with refractory ovarian carcinoma. Gynecol Oncol. 2006 Sep;102(3):425-8. Epub 2006 Jun 23.

Pichelmayer O, Gruenberger B, Zielinski C, Raderer M. Bevacizumab is active in malignant effusion. Ann Oncol. 2006 Dec;17(12):1853. Epub 2006 Jun 21. No abstract available.

Ozcan C, Wong SJ, Hari P. Reversible posterior leukoencephalopathy syndrome and bevacizumab. N Engl J Med. 2006 Mar 2;354(9):980-2; discussion 980-2. No abstract available.

Scappaticci FA, Fehrenbacher L, Cartwright T, Hainsworth JD, Heim W, Berlin J, Kabbinavar F, Novotny W, Sarkar S, Hurwitz H. Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol. 2005 Sep 1;91(3):173-80.

Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006 Dec 14;355(24):2542-50.

Miller KD, Chap LI, Holmes FA, Cobleigh MA, Marcom PK, Fehrenbacher L, Dickler M, Overmoyer BA, Reimann JD, Sing AP, Langmuir V, Rugo HS. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol. 2005 Feb 1;23(4):792-9.

Karp JE, Gojo I, Pili R, Gocke CD, Greer J, Guo C, Qian D, Morris L, Tidwell M, Chen H, Zwiebel J. Targeting vascular endothelial growth factor for relapsed and refractory adult acute myelogenous leukemias: therapy with sequential 1-beta-d-arabinofuranosylcytosine, mitoxantrone, and bevacizumab. Clin Cancer Res. 2004 Jun 1;10(11):3577-85.

Wedam SB, Low JA, Yang SX, Chow CK, Choyke P, Danforth D, Hewitt SM, Berman A, Steinberg SM, Liewehr DJ, Plehn J, Doshi A, Thomasson D, McCarthy N, Koeppen H, Sherman M, Zujewski J, Camphausen K, Chen H, Swain SM. Antiangiogenic and antitumor effects of bevacizumab in patients with inflammatory and locally advanced breast cancer. J Clin Oncol. 2006 Feb 10;24(5):769-77. Epub 2006 Jan 3.

D'Adamo DR, Anderson SE, Albritton K, Yamada J, Riedel E, Scheu K, Schwartz GK, Chen H, Maki RG. Phase II study of doxorubicin and bevacizumab for patients with metastatic soft-tissue sarcomas. J Clin Oncol. 2005 Oct 1;23(28):7135-42.

Responsible Party:	Baylor College of Medicine ( Martha P. Mims )
Study ID Numbers:	H-21728, AVF4534s
Study First Received:	May 21, 2009
Last Updated:	October 1, 2009
ClinicalTrials.gov Identifier:	NCT00908219 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Baylor College of Medicine:

malignant ascites
bevacizumab
vascular endothelial growth factor (VEGF)
paracentesis

Additional relevant MeSH terms:

Pathologic Processes
Antineoplastic Agents
Ascites
Therapeutic Uses
Growth Substances
Physiological Effects of Drugs

Growth Inhibitors
Angiogenesis Modulating Agents
Bevacizumab
Angiogenesis Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 08, 2010