Bevacizumab and Radiation Therapy for Sarcomas

NCT00356031 | Completed Phase 2 Results DMC

• 2 other identifiers: 05-0901R21CA117128-01A1
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Soft Tissue Sarcoma; Fibrous Histiocytoma; Liposarcoma; Leiomyosarcoma; Fibrosarcoma; Synovial Sarcoma

Keywords

Avastin

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Change in Median Microvessel Density (MVD) After Bevacizumab Alone

  baseline and 3 years

• Average Change in Blood Flow, Blood Volume,and Permeability Surface Area

  3 years

• Local Control Rate

  3 years

• Distant Recurrence

  3 years

• Disease Free Survival

  3 years

Study Arms (1)

Bevacizumab, Radiation, and Surgery

EXPERIMENTAL

Bevacizumab 5mg/kg, external beam radiation therapy (XRT), surgery, Intraoperative radiation therapy (IORT), and postoperative external beam radiation therapy (Post-op XRT)

Drug: Bevacizumab; Radiation: Radiation Therapy; Procedure: Surgery

Interventions

Bevacizumab DRUG

Bevacizumab 5mg/kg given intravenously every 2 weeks for a total of 4 doses

Also known as: Avastin

Bevacizumab, Radiation, and Surgery

Radiation Therapy RADIATION

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.

Bevacizumab, Radiation, and Surgery

Surgery PROCEDURE

Surgical resection is performed 6-7 weeks after completion of neoadjuvant therapy.

Bevacizumab, Radiation, and Surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• years of age or older
• Zubrod performance status of 0-2
• Adequate organ and marrow function

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (2)

• Yoon SS, Duda DG, Karl DL, Kim TM, Kambadakone AR, Chen YL, Rothrock C, Rosenberg AE, Nielsen GP, Kirsch DG, Choy E, Harmon DC, Hornicek FJ, Dreyfuss J, Ancukiewicz M, Sahani DV, Park PJ, Jain RK, Delaney TF. Phase II study of neoadjuvant bevacizumab and radiotherapy for resectable soft tissue sarcomas. Int J Radiat Oncol Biol Phys. 2011 Nov 15;81(4):1081-90. doi: 10.1016/j.ijrobp.2010.07.024. Epub 2010 Oct 6.

  PMID: 20932656 RESULT

• Vatner R, James CD, Sathiaseelan V, Bondra KM, Kalapurakal JA, Houghton PJ. Radiation therapy and molecular-targeted agents in preclinical testing for immunotherapy, brain tumors, and sarcomas: Opportunities and challenges. Pediatr Blood Cancer. 2021 May;68 Suppl 2:e28439. doi: 10.1002/pbc.28439. Epub 2020 Aug 22.

  PMID: 32827353 DERIVED

MeSH Terms

Conditions

Sarcoma; Histiocytoma, Benign Fibrous; Liposarcoma; Leiomyosarcoma; Fibrosarcoma; Sarcoma, Synovial

Interventions

Bevacizumab; Radiotherapy; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Histiocytoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Adipose Tissue; Neoplasms, Muscle Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics

Limitations and Caveats

Small number of patients. Results require validation in a larger cohort of patients.

Results Point of Contact

• Title: Dr. Sam S. Yoon, Principal Investigator
• Organization: Massachusetts General Hospital

syoon@partners.org

617 643-9475

Study Officials

• Yen-Lin Chen, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Principal Investigator

Study Record Dates

• First Submitted: July 21, 2006
• First Posted: July 25, 2006
• Study Start: July 1, 2006
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: May 19, 2017
• Results First Posted: May 19, 2017

Record last verified: 2017-04

Locations

US (1)