A Study of Bevacizumab to Prevent Malignant Ascites

NCT00908219 | Withdrawn Phase 2 DMC

• 2 other identifiers: H-21728AVF4534s
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

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).

Conditions

Malignant Ascites

Keywords

malignant ascites; bevacizumab; vascular endothelial growth factor (VEGF); paracentesis

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• 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

• 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

• To assess the effect of anti-VEGF therapy on quality of life in patients with malignant ascites.

  Every three weeks while on-study

Study Arms (1)

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

Interventions

Bevacizumab DRUG

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

Also known as: Avastin; RO4876646

Bevacizumab IV

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Genentech, Inc.: collaborator

Study Sites (3)

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Ben Taub General Hospital

Houston, Texas, 77030, United States

Location

Michael E. DeBakey Veterans Affairs Medical Center

Houston, Texas, 77030, United States

Location

Related Publications (19)

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  BACKGROUND

• 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. doi: 10.1056/NEJMoa032691.

  PMID: 15175435 BACKGROUND

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  PMID: 10769648 BACKGROUND

• 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. doi: 10.1007/s10434-999-0373-0.

  PMID: 10379858 BACKGROUND

• 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. doi: 10.1634/theoncologist.5-suppl_1-45.

  PMID: 10804091 BACKGROUND

• 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.

  PMID: 9635584 BACKGROUND

• 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.

  PMID: 10589746 BACKGROUND

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  PMID: 6823562 BACKGROUND

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  PMID: 16797681 BACKGROUND

• Pichelmayer O, Gruenberger B, Zielinski C, Raderer M. Bevacizumab is active in malignant effusion. Ann Oncol. 2006 Dec;17(12):1853. doi: 10.1093/annonc/mdl143. Epub 2006 Jun 21. No abstract available.

  PMID: 16790519 BACKGROUND

• 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.

  PMID: 16514715 BACKGROUND

• 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. doi: 10.1002/jso.20301.

  PMID: 16118771 BACKGROUND

• 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. doi: 10.1056/NEJMoa061884.

  PMID: 17167137 BACKGROUND

• 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. doi: 10.1200/JCO.2005.05.098.

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• 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. doi: 10.1158/1078-0432.CCR-03-0627.

  PMID: 15173063 BACKGROUND

• 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. doi: 10.1200/JCO.2005.03.4645. Epub 2006 Jan 3.

  PMID: 16391297 BACKGROUND

• 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. doi: 10.1200/JCO.2005.16.139.

  PMID: 16192597 BACKGROUND

MeSH Terms

Interventions

Bevacizumab

Intervention Hierarchy (Ancestors)

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

Study Officials

• Martha P Mims, MD, PhD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 21, 2009
• First Posted: May 25, 2009
• Study Start: July 1, 2009
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: June 3, 2015

Record last verified: 2012-02

Locations

US (3)