Bevacizumab in Treating Patients With Angiosarcoma

An Open Label Multicenter Phase II Study of Bevacizumab for the Treatment of Angiosarcoma

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well bevacizumab works in treating patients with angiosarcoma.

Study Overview

• Status: Completed
• Conditions: Sarcoma
• Intervention / Treatment: Biological: Bevacizumab

Detailed Description

OBJECTIVES:

Primary

• Determine the median progression-free survival, in terms of stable disease, of patients with newly diagnosed or recurrent/refractory angiosarcoma treated with bevacizumab.

Secondary

• Evaluate the treatment effect of bevacizumab on the objective response rate as assessed by modified RECIST criteria in patients with angiosarcoma.
• Evaluate the duration of response.
• Assess the treatment effect of bevacizumab on duration of overall survival.
• Explore the objective response by target tumor density changes on CT scan.
• Evaluate the safety and tolerability of bevacizumab in patients with angiosarcoma.

OUTLINE: This is an open-label, multicenter study.

Patients receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 to 4 months for 2 years.

PROJECTED ACCRUAL: A total of 31 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093-0658
      • Rebecca and John Moores UCSD Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60611-3013
      • Robert H. Lurie Comprehensive Cancer Center at Northwestern University
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Fox Chase Cancer Center CCOP Research Base
  • Texas
    • Houston, Texas, United States, 77030-4009
      • M. D. Anderson Cancer Center at University of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed angiosarcoma

  • Any stage disease
  • Must be deemed not surgically resectable (complete resection) and/or no other therapeutic modality is known to be curative
  • No angiosarcoma of a vessel wall
• Newly diagnosed or recurrent/refractory disease
• No prior tumor-related hemorrhage (any grade)
• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan
• No CNS disease, brain metastases, or primary brain tumors

PATIENT CHARACTERISTICS:

• ECOG performance status of 0 or 1
• Absolute granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 gm/dL (transfusion and epoetin alfa allowed)
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Urine protein:creatinine ratio ≤ 1.0
• Total bilirubin ≤ 1.5 mg/dL
• Aspartate aminotransferase < 5 times ULN
• Alkaline phosphatase < 5 times ULN
• PT/INR ≤ 1.5 times ULN
• PTT ≤ 1.5 times ULN
• Fertile patients must use effective contraception
• Ejection fraction > 49% for patients with prior anthracycline therapy, ischemic cardiac disease, or history of heart failure
• No uncontrolled active infection
• No uncontrolled high blood pressure (defined as > 150/100 mm Hg)
• No symptomatic congestive heart failure (New York Heart Association class II-IV), unstable angina, cardiac arrhythmia, or myocardial infarction within the past 6 months
• No psychiatric illness or social situation that would limit study compliance
• No serious, nonhealing wound, ulcer, or bone fracture
• No evidence of bleeding diathesis or coagulopathy
• No clinically significant peripheral vascular disease
• Not pregnant or nursing
• No seizures not controlled with standard medical therapy
• No embolic or hemorrhagic stroke or prior transient ischemic attack
• No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
• No significant traumatic injury within the past 6 weeks

PRIOR CONCURRENT THERAPY:

• No prior therapy with bevacizumab or other antiangiogenesis treatment
• No major surgical procedure or open biopsy within the past 6 weeks
• No more than 2 prior chemotherapy regimens
• No fine-needle aspiration or core-needle biopsy or other minor surgical procedure within the past 7 days
• No radiotherapy within the past 28 days
• No concurrent chronic daily treatment with aspirin > 325 mg/day or nonsteroidal anti-inflammatory medications
• No concurrent warfarin or any other anticoagulant (any dose)
• No concurrent radiotherapy
• No concurrent major surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bevacizumab; Bevacizumab treatment until disease progression or intolerance	Biological: Bevacizumab; Bevacizumab 15 mg/kg IV infusion given on day 1 every 21 days = (1 cycle).; Other Names: Avastin; rhuMAb; VEGF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Progression-free Survival of Patients Treated With the Study Drug as Defined by RECIST Criteria.	During treatment, tumor assessment was done by MRI scan after the second cycle of study treatment, after the forth cycle of study treatment, and then every 3 cycles of treatment thereafter. After Study drug completion, tumor assessment by MRI was done every 3 to 4 months (for up to 2 years after the last bevacizumab dosage). Responses were categorized according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.0. Progressive Disease (PD) was defined as having at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.	After cycles 2 and 4, then every 3 cycles thereafter while on treatment (1 cycle = 21 days); every 3-4 months after treatment up to 2 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate in Patients Treated With Bevacizumab.	Objective response rate will be measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. Stable Disease, neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study. Progressive Disease, defined as having at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.	After cycles 2 and 4, then every 3 cycles thereafter while on treatment (1 cycle = 21 days); every 3-4 months after treatment up to 2 years.
Duration of Response.	During treatment, evaluation of response will be done by MRI scan after the second cycle of study treatment, after the forth cycle of study treatment, and then every 3 cycles of treatment. After Study drug completion, evaluation of response will be assessed by MRI every 3 to 4 months (for 2 years after the last bevacizumab dosage).	After cycles 2 and 4, then every 3 cycles thereafter while on treatment (1 cycle = 21 days); every 3-4 months after treatment up to 2 years.
Assess the Treatment Effect of Bevacizumab on Duration of Overall Survival	After Study drug completion, assessment of treatment effect of bevacizumab on duration of overall survival will be assessed by MRI every 3 to 4 months (for 2 years after the last bevacizumab dosage).	After cycles 2 and 4, then every 3 cycles thereafter while on treatment (1 cycle = 21 days); every 3-4 months after treatment up to 2 years
Evaluate the Toxicity of Bevacizumab.	Toxicity data for bevacizumab will be collected on day 1 of every cycle (1 cycle = 21 days) during treatment according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). In general adverse events (AEs) will be graded according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE	Day 1 of every cycle, on average every 21 days until end of treatment up to 2 years.

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Mark Agulnik, MD, Northwestern University

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): June 6, 2013
• Study Completion (Actual): November 10, 2016

Study Registration Dates

• First Submitted: February 6, 2006
• First Submitted That Met QC Criteria: February 6, 2006
• First Posted (Estimate): February 7, 2006

Study Record Updates

• Last Update Posted (Actual): June 25, 2018
• Last Update Submitted That Met QC Criteria: June 20, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: adult angiosarcoma; stage IV adult soft tissue sarcoma; recurrent adult soft tissue sarcoma; stage III adult soft tissue sarcoma; stage II adult soft tissue sarcoma; stage I adult soft tissue sarcoma
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; Sarcoma; Hemangiosarcoma; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: NU 04S1 (Other Identifier: Northwestern University); STU00006784 (Other Identifier: Northwestern University IRB)