Clinical trial NCT00356031: Bevacizumab and Radiation Therapy for Sarcomas
Official title: A Phase II Study of Neoadjuvant Bevacizumab and Radiation Therapy for Resectable Soft Tissue Sarcomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Soft Tissue Sarcoma
Fibrous Histiocytoma
Liposarcoma
Leiomyosarcoma
Fibrosarcoma
Synovial Sarcoma
Keywords: Avastin
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
First posted: 2006-07-25
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Objective Response Rate for Neoadjuvant Bevacizumab Combined With Radiation Therapy for Intermediate and High-risk Soft Tissue Sarcomas.
timeFrame: 3 years
Secondary outcomes:
measure: Change in Median Microvessel Density (MVD) After Bevacizumab Alone
timeFrame: baseline and 3 years
measure: Average Change in Blood Flow, Blood Volume,and Permeability Surface Area
timeFrame: 3 years
measure: Local Control Rate
timeFrame: 3 years
measure: Distant Recurrence
timeFrame: 3 years
measure: Disease Free Survival
timeFrame: 3 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Yen-Lin Chen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.