Bevacizumab and Radiation Therapy for Sarcomas

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase II Study of Neoadjuvant Bevacizumab and Radiation Therapy for Resectable Soft Tissue Sarcomas

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

Intervention / Treatment
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* Drug: Bevacizumab
* Radiation: Radiation Therapy
* Procedure: Surgery


Participation Criteria
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Eligibility Criteria
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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

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bevacizumab, Radiation, and Surgery<br>Bevacizumab 5mg/kg, external beam radiation therapy (XRT), surgery, Intraoperative radiation therapy (IORT), and postoperative external beam radiation therapy (Post-op XRT) | Drug: Bevacizumab<br>* Bevacizumab 5mg/kg given intravenously every 2 weeks for a total of 4 doses<br>* Other names: Avastin;Radiation: Radiation Therapy<br>* External beam radiation given two weeks after the first bevacizumab infusion and delivered 5 days a week at 1.8 Gy per day, over 6 weeks. Total radiation dose is 50.4 Gy. For patients with tumors in the retroperitoneum or pelvis, intraoperative radiation therapy (10-20 Gy) may be given for close or positive margins at the discretion of the radiation oncologist and surgeon. For patients with tumors in the extremity or trunk, post-operative external beam radiation therapy (10-20 Gy) will be given for close or positive margins assuming wound healing is good.<br>Procedure: Surgery<br>* Surgical resection is performed 6-7 weeks after completion of neoadjuvant therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Median Microvessel Density (MVD) After Bevacizumab Alone | The percentage change in median microvessel density (MVD) after Bevacizumab treatment alone | baseline and 3 years | 
| Average Change in Blood Flow, Blood Volume,and Permeability Surface Area | 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. | 3 years | 
| Local Control Rate | 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. | 3 years | 
| Distant Recurrence | 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. | 3 years | 
| Disease Free Survival | 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. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Avastin