A Study of Bevacizumab to Prevent Malignant Ascites

Malignant Ascites Clinical Trial

Official title:

A Prospective, Phase II Trial of Intravenous Bevacizumab (Avastin) for the Prevention of Recurrent Malignant Ascites

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00908219
• Other study ID #: H-21728
• Secondary ID: AVF4534s
• Status: Withdrawn
• Phase: Phase 2
• First received: May 21, 2009
• Last updated: June 2, 2015
• Start date: July 2009
• Est. completion date: February 2011

Study information

• Verified date: February 2012
• Source: Baylor College of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Ascites
• Malignant Ascites

Intervention

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

Locations

Country	Name	City	State
United States	Baylor College of Medicine	Houston	Texas
United States	Ben Taub General Hospital	Houston	Texas
United States	Michael E. DeBakey Veterans Affairs Medical Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Baylor College of Medicine	Genentech, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (19)

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum in: N Engl J Med. 2007 Jan 18;356(3):318. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the repeat paracentesis response rate defined as a doubling of the patient's baseline time to repeat paracentesis.		12 weeks after initiation of study treatment	No
Secondary	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.		Unspecified - depends upon when subject will need repeat paracentesis	No
Secondary	To analyze the mean number of paracentesis procedures required in each patient over the course of three months.		12 weeks after the initiation of study treatment	No
Secondary	To assess the effect of anti-VEGF therapy on quality of life in patients with malignant ascites.		Every three weeks while on-study	No