Doxorubicin and Bevacizumab in Treating Patients With Locally Recurrent or Metastatic Soft Tissue Sarcoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Bevacizumab may stop the growth of tumor cells by stopping blood flow to the tumor. Combining doxorubicin with bevacizumab may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining doxorubicin with bevacizumab in treating patients who have locally recurrent or metastatic soft tissue sarcoma.

Detailed Description
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OBJECTIVES: Determine the response rate (partial and complete) in patients with locally recurrent or metastatic soft tissue sarcoma treated with doxorubicin and bevacizumab. Determine the tolerability of this regimen in these patients. Determine the toxicity profile of this regimen in these patients. Determine whether pre-treatment plasma vascular endothelial growth factor level or microvessel density of tumor samples from these patients predicts response to this regimen. OUTLINE: This is a multicenter study. Patients receive doxorubicin IV over 5-10 minutes followed by bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with responding disease after reaching the maximum dose of doxorubicin may continue bevacizumab alone. Patients are followed every 3 months for 1 year. PROJECTED ACCRUAL: A total of 17-37 patients will be accrued for this study within 13.3 months.

Official Title
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A Multi-Institutional, Open-Label, Phase II Study Of Doxorubicin And Bevacizumab (Anti-VEFG Monoclonal Antibody, NSC 704865) For Patients With Advanced Or Metastatic Soft-Tissue Sarcoma

Conditions
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Sarcoma

Intervention / Treatment
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* Biological: bevacizumab
* Drug: doxorubicin hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed soft tissue sarcoma Locally recurrent or metastatic disease At least 1 unidimensionally measurable lesion At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan No prior or concurrent known brain metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 80-100% OR ECOG 0-1 Life expectancy Not specified Hematopoietic Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 No bleeding diathesis or coagulopathy Hepatic Bilirubin no greater than 1.2 mg/dL AST and ALT no greater than 2.5 times upper limit of normal PT and aPTT normal Renal Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 60 mL/min No proteinuria (must be less than 500 mg protein per 24 hours) Cardiovascular Cardiac ejection fraction at least 50% by echocardiogram or MUGA No history of deep vein thrombosis No clinically significant cardiovascular disease No uncontrolled hypertension No myocardial infarction No unstable angina No New York Heart Association grade II-IV congestive heart failure No serious cardiac arrhythmia requiring medication No grade II or greater peripheral vascular disease within the past year Pulmonary No history of pulmonary embolism Other No symptomatic peripheral neuropathy grade 2 or greater No other neoplastic disease within the past 5 years except curatively treated basal cell skin cancer or carcinoma in situ of the cervix No prior allergic reactions attributed to compounds of similar chemical or biological composition to bevacizumab (including products derived from Chinese hamster ovary cells), doxorubicin, or dexrazoxane No HIV-positive patients receiving combination antiretroviral therapy No ongoing or active infection No psychiatric illness or social situations that would preclude study entry No other uncontrolled concurrent illness No serious, non-healing wound ulcer or bone fracture No significant traumatic injury within the past 3 weeks Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy See Chemotherapy At least 4 weeks since prior immunotherapy and recovered No other concurrent immunotherapy Chemotherapy No prior doxorubicin or any other anthracyclines No more than 1 prior chemotherapy regimen The following are not considered prior chemotherapy: Immunotherapy, including cytokines Peroxisome-proliferator-activated receptor gamma agonists or thalidomide At least 4 weeks since prior chemotherapy (6 weeks for carmustine or mitomycin) and recovered No other concurrent chemotherapy Endocrine therapy Not specified Radiotherapy At least 4 weeks since prior radiotherapy and recovered No concurrent radiotherapy Surgery At least 3 weeks since prior major surgical procedure or open biopsy At least 1 week since prior needle biopsy Other No other concurrent investigational agents No concurrent full-dose anticoagulants (except to maintain patency of preexisting, permanent indwelling IV catheters) or thrombolytic agent Concurrent warfarin allowed if INR less than 1.5 No concurrent chronic daily aspirin (more than 325 mg/day) or nonsteroidal anti -inflammatory medications known to inhibit platelet function No other concurrent investigational or commercial agents or therapies for this malignancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: bevacizumab|nan|
|Drug: doxorubicin hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult soft tissue sarcoma, stage III adult soft tissue sarcoma, stage IV adult soft tissue sarcoma