Bevacizumab and Radiation Therapy for Sarcomas

April 14, 2017 updated by: Yen-Lin Evelyn Chen, MD, Massachusetts General Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Bevacizumab, Radiation, and Surgery
Bevacizumab 5mg/kg, external beam radiation therapy (XRT), surgery, Intraoperative radiation therapy (IORT), and postoperative external beam radiation therapy (Post-op XRT)
Drug: Bevacizumab
Bevacizumab 5mg/kg given intravenously every 2 weeks for a total of 4 doses
Other Names:
  • Avastin
Radiation: Radiation Therapy
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.
Procedure: Surgery
Surgical resection is performed 6-7 weeks after completion of neoadjuvant therapy.

What is the study measuring?

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.
Time Frame: 3 years
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
Time Frame: baseline and 3 years
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
Time Frame: 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.
3 years
Local Control Rate
Time Frame: 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.
3 years
Distant Recurrence
Time Frame: 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.
3 years
Disease Free Survival
Time Frame: 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.
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Collaborators

National Cancer Institute (NCI)
National Institutes of Health (NIH)

Investigators

  • Principal Investigator: Yen-Lin Chen, MD, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2006

Primary Completion (Actual)

March 1, 2010

Study Completion (Actual)

March 1, 2010

Study Registration Dates

First Submitted

July 21, 2006

First Submitted That Met QC Criteria

July 21, 2006

First Posted (Estimate)

July 25, 2006

Study Record Updates

Last Update Posted (Actual)

May 19, 2017

Last Update Submitted That Met QC Criteria

April 14, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 05-090
  • 1R21CA117128-01A1 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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