Bevacizumab and Radiation Therapy for Sarcomas

Phase 2

Completed

Conditions: Soft Tissue Sarcoma
Fibrosarcoma
Liposarcoma
Synovial Sarcoma
Fibrous Histiocytoma
Leiomyosarcoma

Interventions: Drug: Bevacizumab
Radiation: Radiation Therapy
Procedure: Surgery

Brief Summary: The main purpose of this study is to test the effectiveness of bevacizumab in combination with radiation therapy to see what effects (good or bad) they have on patients with soft tissue sarcoma. Bevacizumab is an antibody designed specifically to slow or stop the growth of cancerous tumors by decreasing the blood supply to the tumor. Bevacizumab is approved by the FDA in combination with intravenous 5-fluorouracil-based chemotherapy as a treatment for patients with cancer of the colon or rectum that has spread. However, the use of bevacizumab in combination with radiation for sarcomas is still under investigation.

Detailed Description: * The dose of bevacizumab and radiation therapy will be the same for all participants throughout the study.

* Bevacizumab will be given as an intravenous infusion every 2 weeks for a total of 4 doses.

* Radiation therapy will begin 2 weeks after the first bevacizumab infusion and will be delivered 5 days per week over a period of 6 weeks. This is done as an outpatient procedure. Each 2 week period will be considered a separate treatment cycle. Participants will be treated with radiation therapy for a maximum of 3 cycles (6 weeks).

* A surgeon will evaluate the participants tumor by radiologic studies before study treatment to determine if surgical removal is possible. After the completion of study treatment, a surgeon will repeat the evaluation of the tumor. Surgery will performed 6-7 weeks after the completion of radiation therapy.

Recruitment & Eligibility

Inclusion Criteria

Primary soft tissue sarcoma (STS) or an isolated local recurrence of STS. Open incisional biopsy or core biopsies should be performed within 8 weeks prior to registration
Tumor grade of intermediate or high grade
Tumor must be located on the upper extremity, the lower extremity, trunk, retroperitoneum, or pelvis
Primary tumors must be > 5.0cm in maximal diameter and local recurrence can be any size
18 years of age or older
Zubrod performance status of 0-2
Adequate organ and marrow function

Exclusion Criteria

Metastatic disease
Pregnant or lactating women
HIV positive patients
Prior treatment with radiation, chemotherapy or biotherapy for this tumor
History or evidence of central nervous system (CNS) disease
Serious, non-healing wound, ulcer, or bone fracture
Clinically significant cardiovascular disease, New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or Grade II or greater peripheral vascular disease within 1 year
History of stroke within the past 6 months
Major surgical procedure or significant traumatic injury within 28 days
Current or recent (within 10 days) use of full-dose oral or parenteral anticoagulants or thrombolytic agents.
Presence of bleeding diathesis or coagulopathy
Proteinuria at baseline or clinically significant impairment of renal function
History of abdominal fistula, gastrointestinal perforation, or inta-abdominal abscess within the past 6 months
Documented history of uncontrolled seizures
Grade 2 or greater sensory neuropathy based upon the NCI CTCAE, version 3.0
Known history of deep vein thrombosis or pulmonary embolus
Known hypercoagulable disorder
History of hepatic cirrhosis or current hepatic dysfunction

Arm && Interventions

Group	Intervention	Description
Bevacizumab, Radiation, and Surgery	Radiation Therapy	Bevacizumab 5mg/kg, external beam radiation therapy (XRT), surgery, Intraoperative radiation therapy (IORT), and postoperative external beam radiation therapy (Post-op XRT)
Bevacizumab, Radiation, and Surgery	Surgery	Bevacizumab 5mg/kg, external beam radiation therapy (XRT), surgery, Intraoperative radiation therapy (IORT), and postoperative external beam radiation therapy (Post-op XRT)
Bevacizumab, Radiation, and Surgery	Bevacizumab	Bevacizumab 5mg/kg, external beam radiation therapy (XRT), surgery, Intraoperative radiation therapy (IORT), and postoperative external beam radiation therapy (Post-op XRT)

Primary Outcome Measures

Name	Time	Method
Objective Response Rate for Neoadjuvant Bevacizumab Combined With Radiation Therapy for Intermediate and High-risk Soft Tissue Sarcomas.	3 years	The count of participants with greater than or equal to 80% pathological necrosis in the resected specimen following neoadjuvant bevacizumab and radiation.

Secondary Outcome Measures

Name	Time	Method
Distant Recurrence	3 years	The number of participants with distant recurrence at the time of last follow-up. Distant recurrence is when cancer has spread (metastasized) to areas farther away from where the primary cancer site is.
Disease Free Survival	3 years	The median amount of time from the end of treatment until to distant recurrence. Distant recurrence is when cancer spreads to areas in the body away from the primary cancer site.
Local Control Rate	3 years	The number of patients with local recurrence after a median follow-up of 24 months. Local recurrence is defined as disease progression (new cancer growth) at the primary cancer site.
Average Change in Blood Flow, Blood Volume,and Permeability Surface Area	3 years	The percentage reduction in blood flow, blood volume,and permeability surface area of the tumor following combination therapy as determined by perfusion CT (computerized tomography) scan. The percent change represents the combined average percent change for flow, volume, and permeability together.
Change in Median Microvessel Density (MVD) After Bevacizumab Alone	baseline and 3 years	The percentage change in median microvessel density (MVD) after Bevacizumab treatment alone