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Bevacizumab and Radiation Therapy for Sarcomas

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ClinicalTrials.gov Identifier: NCT00356031
Recruitment Status : Completed
First Posted : July 25, 2006
Results First Posted : May 19, 2017
Last Update Posted : May 19, 2017
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Yen-Lin Evelyn Chen, MD, Massachusetts General Hospital

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Soft Tissue Sarcoma
Fibrous Histiocytoma
Liposarcoma
Leiomyosarcoma
Fibrosarcoma
Synovial Sarcoma
Interventions Drug: Bevacizumab
Radiation: Radiation Therapy
Procedure: Surgery
Enrollment 20

Recruitment Details Subjects were recruited from the multidisciplinary sarcoma clinic, surgical oncology, radiation oncology, and medical oncology clinics at the Massachusetts General Hospital, Brigham and Women’s Hospital, or Dana-Farber Cancer Institute.
Pre-assignment Details  
Arm/Group Title Experimental: Bevacizumab, Radiation, and Surgery
Hide Arm/Group Description

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

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

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.

Surgery: Surgery is performed 6-7 weeks after completion of neoadjuvant therapy.

Period Title: Overall Study
Started 20
Completed 20
Not Completed 0
Arm/Group Title Bevacizumab, Radiation, and Surgery
Hide Arm/Group Description

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

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

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.

Surgery: Surgery is performed 6-7 weeks after completion of neoadjuvant therapy.

Overall Number of Baseline Participants 20
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
<=18 years
0
   0.0%
Between 18 and 65 years
16
  80.0%
>=65 years
4
  20.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 20 participants
54  (13)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
Female
7
  35.0%
Male
13
  65.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 20 participants
20
Sarcoma Histology  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
Fibroblastic
8
  40.0%
Liposarcoma
6
  30.0%
Leiomyosarcoma
4
  20.0%
Fibroblastic Osteosarcoma
1
   5.0%
Not Otherwise Specified
1
   5.0%
Sarcoma Grade  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
Low
2
  10.0%
Intermediate
8
  40.0%
High
10
  50.0%
Median Sarcoma Size  
Median (Full Range)
Unit of measure:  Centimeters (cm)
Number Analyzed 20 participants
8.25
(5 to 20.2)
Sarcoma Location  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
Extremity
13
  65.0%
Trunk
1
   5.0%
retroperitoneal/pelvis tumors
6
  30.0%
1.Primary Outcome
Title Objective Response Rate for Neoadjuvant Bevacizumab Combined With Radiation Therapy for Intermediate and High-risk Soft Tissue Sarcomas.
Hide Description The count of participants with greater than or equal to 80% pathological necrosis in the resected specimen following neoadjuvant bevacizumab and radiation.
Time Frame 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Bevacizumab, Radiation, and Surgery
Hide Arm/Group Description:

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

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

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.

Surgery: Surgery is performed 6-7 weeks after completion of neoadjuvant therapy.

Overall Number of Participants Analyzed 20
Measure Type: Number
Unit of Measure: participants
80–89% necrosis 2
90–99% necrosis 4
100% necrosis 3
2.Secondary Outcome
Title Change in Median Microvessel Density (MVD) After Bevacizumab Alone
Hide Description The percentage change in median microvessel density (MVD) after Bevacizumab treatment alone
Time Frame baseline and 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Bevacizumab, Radiation, and Surgery
Hide Arm/Group Description:

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

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

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.

Surgery: Surgery is performed 6-7 weeks after completion of neoadjuvant therapy.

Overall Number of Participants Analyzed 20
Median (95% Confidence Interval)
Unit of Measure: percentage of change in MVD
53
(28.6 to 77.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bevacizumab, Radiation, and Surgery
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.05
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
3.Secondary Outcome
Title Average Change in Blood Flow, Blood Volume,and Permeability Surface Area
Hide Description 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.
Time Frame 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Bevacizumab, Radiation, and Surgery
Hide Arm/Group Description:

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

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

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.

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

Overall Number of Participants Analyzed 20
Mean (Full Range)
Unit of Measure: Percent Reduction
67
(62 to 72)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bevacizumab, Radiation, and Surgery
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.05
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
4.Secondary Outcome
Title Local Control Rate
Hide Description 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.
Time Frame 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Bevacizumab, Radiation, and Surgery
Hide Arm/Group Description:

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

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

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.

Surgery: Surgery is performed 6-7 weeks after completion of neoadjuvant therapy.

Overall Number of Participants Analyzed 20
Measure Type: Count of Participants
Unit of Measure: Participants
Local Recurrence
1
   5.0%
No Local Recurrence
19
  95.0%
5.Secondary Outcome
Title Distant Recurrence
Hide Description 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.
Time Frame 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Experimental: Bevacizumab, Radiation, and Surgery
Hide Arm/Group Description:

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

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

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.

Surgery: Surgery is performed 6-7 weeks after completion of neoadjuvant therapy.

Overall Number of Participants Analyzed 20
Measure Type: Count of Participants
Unit of Measure: Participants
Distant recurrence
7
  35.0%
No distant recurrence
13
  65.0%
6.Secondary Outcome
Title Disease Free Survival
Hide Description 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.
Time Frame 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Experimental: Bevacizumab, Radiation, and Surgery
Hide Arm/Group Description:

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

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

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.

Surgery: Surgery is performed 6-7 weeks after completion of neoadjuvant therapy.

Overall Number of Participants Analyzed 20
Median (Full Range)
Unit of Measure: Months
7
(2 to 36)
Time Frame 3 years
Adverse Event Reporting Description Laboratory tests and physical exams were performed as a part of routine study visits.
 
Arm/Group Title Bevacizumab, Radiation, and Surgery
Hide Arm/Group Description

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

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

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.

Surgery: Surgery is performed 6-7 weeks after completion of neoadjuvant therapy.

All-Cause Mortality
Bevacizumab, Radiation, and Surgery
Affected / at Risk (%)
Total   3/20 (15.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Bevacizumab, Radiation, and Surgery
Affected / at Risk (%) # Events
Total   3/20 (15.00%)    
Blood and lymphatic system disorders   
Lymphopenia  1  1/20 (5.00%)  1
Metabolism and nutrition disorders   
Hyponatremia  1  1/20 (5.00%)  1
Reproductive system and breast disorders   
Dyspnea  1  1/20 (5.00%)  1
Vascular disorders   
Thrombosis/thrombus/embolism  1  1/20 (5.00%)  1
1
Term from vocabulary, CTCAE (3.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Bevacizumab, Radiation, and Surgery
Affected / at Risk (%) # Events
Total   20/20 (100.00%)    
Blood and lymphatic system disorders   
Hemoglobin  1  10/20 (50.00%)  23
Leukocytes  1  3/20 (15.00%)  15
Lymphopenia  1  7/20 (35.00%)  21
Neutrophils  1  3/20 (15.00%)  5
Platelets  1  2/20 (10.00%)  4
Partial thromboplastin time  1  3/20 (15.00%)  4
Hematoma  1  2/20 (10.00%)  2
Nose, hemorrhage  1  3/20 (15.00%)  6
Hemorrhage-other  1  1/20 (5.00%)  1
Edema limb  1  2/20 (10.00%)  3
Cardiac disorders   
Palpitations  1  1/20 (5.00%)  1
Sinus tachycardia  1  1/20 (5.00%)  1
Hypertension  1  10/20 (50.00%)  49
Hypotension  1  1/20 (5.00%)  1
Left ventricular systolic dysfunction  1  1/20 (5.00%)  1
Gastrointestinal disorders   
Anorexia  1  3/20 (15.00%)  4
Constipation  1  3/20 (15.00%)  5
Dehydration  1  1/20 (5.00%)  2
Diarrhea w/o prior colostomy  1  6/20 (30.00%)  10
Dry mouth  1  1/20 (5.00%)  2
Dysphagia  1  1/20 (5.00%)  1
Flatulence  1  1/20 (5.00%)  3
Hemorrhoids  1  1/20 (5.00%)  2
Muco/stomatitis (symptom) oral cavity  1  1/20 (5.00%)  4
Nausea  1  8/20 (40.00%)  12
Taste disturbance  1  1/20 (5.00%)  1
Vomiting  1  1/20 (5.00%)  1
GI-other  1  2/20 (10.00%)  4
Throat/pharynx/larynx, pain  1  2/20 (10.00%)  2
General disorders   
Fatigue  1  11/20 (55.00%)  40
Fever w/o neutropenia  1  2/20 (10.00%)  2
Insomnia  1  4/20 (20.00%)  5
Abdomen, pain  1  1/20 (5.00%)  1
Head/headache  1  3/20 (15.00%)  7
Pain-other  1  3/20 (15.00%)  3
Immune system disorders   
Allergic reaction  1  3/20 (15.00%)  12
Allergic rhinitis  1  3/20 (15.00%)  5
Infections and infestations   
Infection Gr0-2 neut, skin  1  1/20 (5.00%)  2
Infection Gr0-2 neut, stomach  1  1/20 (5.00%)  1
Infection Gr0-2 neut, urinary tract  1  1/20 (5.00%)  1
Infection Gr0-2 neut, vagina  1  1/20 (5.00%)  1
Infection Gr0-2 neut, wound  1  1/20 (5.00%)  2
Infection w/ unk ANC urinary tract NOS  1  1/20 (5.00%)  2
Metabolism and nutrition disorders   
Hypoalbuminemia  1  2/20 (10.00%)  3
Alkaline phosphatase  1  4/20 (20.00%)  18
ALT, SGPT  1  2/20 (10.00%)  8
AST, SGOT  1  3/20 (15.00%)  8
Bilirubin  1  1/20 (5.00%)  3
Hypercalcemia  1  1/20 (5.00%)  1
Hypocalcemia  1  3/20 (15.00%)  4
Hyperglycemia  1  13/20 (65.00%)  28
Hypoglycemia  1  2/20 (10.00%)  2
Hypermagnesemia  1  2/20 (10.00%)  2
Hypomagnesemia  1  2/20 (10.00%)  2
Hypophosphatemia  1  6/20 (30.00%)  10
Hyperkalemia  1  1/20 (5.00%)  2
Hypokalemia  1  2/20 (10.00%)  4
Proteinuria  1  4/20 (20.00%)  12
Hyponatremia  1  3/20 (15.00%)  5
Metabolic/Laboratory-other  1  1/20 (5.00%)  12
Musculoskeletal and connective tissue disorders   
Nonneuropathic lower extr muscle weak  1  1/20 (5.00%)  1
Soft tissue necrosis, extremity lower  1  1/20 (5.00%)  3
Musculoskeletal/soft tissue-other  1  3/20 (15.00%)  8
Back, pain  1  3/20 (15.00%)  7
Extremity-limb, pain  1  3/20 (15.00%)  8
Joint, pain  1  3/20 (15.00%)  8
Pelvic, pain  1  1/20 (5.00%)  3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Tumor pain  1  2/20 (10.00%)  2
Tumor lysis syndrome  1  1/20 (5.00%)  1
Nervous system disorders   
Anxiety  1  1/20 (5.00%)  4
Depression  1  3/20 (15.00%)  5
Neuropathy-sensory  1  2/20 (10.00%)  11
Neurologic-other  1  1/20 (5.00%)  2
Reproductive system and breast disorders   
Irregular menses  1  2/20 (10.00%)  4
Respiratory, thoracic and mediastinal disorders   
Chest/thoracic pain NOS  1  1/20 (5.00%)  1
Dyspnea  1  1/20 (5.00%)  4
Nasal cavity/paranasal sinus reaction  1  1/20 (5.00%)  1
Voice changes/dysarthria  1  1/20 (5.00%)  1
Pulmonary/Upper Respiratory-other  1  2/20 (10.00%)  6
Skin and subcutaneous tissue disorders   
Hyperpigmentation  1  1/20 (5.00%)  1
Rash/desquamation  1  3/20 (15.00%)  9
Rash: acne/acneiform  1  1/20 (5.00%)  2
Radiation dermatitis  1  3/20 (15.00%)  4
Erythema multiforme  1  3/20 (15.00%)  5
Wound - non-infectious  1  2/20 (10.00%)  2
Skin-other  1  5/20 (25.00%)  17
Skin, pain  1  1/20 (5.00%)  1
Vascular disorders   
Phlebitis  1  1/20 (5.00%)  1
Thrombosis/thrombus/embolism  1  1/20 (5.00%)  1
Visceral arterial ischemia  1  1/20 (5.00%)  1
1
Term from vocabulary, CTCAE (3.0)
Indicates events were collected by systematic assessment
Small number of patients. Results require validation in a larger cohort of patients.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. Sam S. Yoon, Principal Investigator
Organization: Massachusetts General Hospital
Phone: 617 643-9475
Responsible Party: Yen-Lin Evelyn Chen, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00356031     History of Changes
Other Study ID Numbers: 05-090
1R21CA117128-01A1 ( U.S. NIH Grant/Contract )
First Submitted: July 21, 2006
First Posted: July 25, 2006
Results First Submitted: February 16, 2017
Results First Posted: May 19, 2017
Last Update Posted: May 19, 2017