Clinical trial NCT00288015: Bevacizumab in Treating Patients With Angiosarcoma
Official title: An Open Label Multicenter Phase II Study of Bevacizumab for the Treatment of Angiosarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sarcoma
Keywords: adult angiosarcoma
recurrent adult soft tissue sarcoma
stage I adult soft tissue sarcoma
stage II adult soft tissue sarcoma
stage III adult soft tissue sarcoma
stage IV adult soft tissue sarcoma
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2006-02-07
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Median Progression-free Survival of Patients Treated With the Study Drug as Defined by RECIST Criteria.
timeFrame: 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 outcomes:
measure: Objective Response Rate in Patients Treated With Bevacizumab.
timeFrame: 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.
measure: Duration of Response.
timeFrame: 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.
measure: Assess the Treatment Effect of Bevacizumab on Duration of Overall Survival
timeFrame: 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
measure: Evaluate the Toxicity of Bevacizumab.
timeFrame: Day 1 of every cycle, on average every 21 days until end of treatment up to 2 years.
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center CCOP Research Base
state: Pennsylvania
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
Study officials:
affiliation: Northwestern University
name: Mark Agulnik, MD
role: PRINCIPAL_INVESTIGATOR
References: