Fibrosarcoma, Fibrous Histiocytoma, Leiomyosarcoma, Liposarcoma, Soft Tissue Sarcoma, Synovial Sarcoma
Conditions
Keywords
Avastin
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.
Interventions
DRUGBevacizumab
Bevacizumab 5mg/kg given intravenously every 2 weeks for a total of 4 doses
RADIATIONRadiation 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.
PROCEDURESurgery
Surgical resection is performed 6-7 weeks after completion of neoadjuvant therapy.
Sponsors
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate for Neoadjuvant Bevacizumab Combined With Radiation Therapy for Intermediate and High-risk Soft Tissue Sarcomas. | 3 years | The count of participants with greater than or equal to 80% pathological necrosis in the resected specimen following neoadjuvant bevacizumab and radiation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Median Microvessel Density (MVD) After Bevacizumab Alone | baseline and 3 years | The percentage change in median microvessel density (MVD) after Bevacizumab treatment alone |
| Average Change in Blood Flow, Blood Volume,and Permeability Surface Area | 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. |
| Local Control Rate | 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. |
| Distant Recurrence | 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. |
| Disease Free Survival | 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. |
Countries
United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| 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)
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. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Bevacizumab, Radiation, and Surgery |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age, Continuous | 54 years STANDARD_DEVIATION 13 |
| Median Sarcoma Size | 8.25 Centimeters (cm) |
| Region of Enrollment United States | 20 participants |
| Sarcoma Grade High | 10 Participants |
| Sarcoma Grade Intermediate | 8 Participants |
| Sarcoma Grade Low | 2 Participants |
| Sarcoma Histology Fibroblastic | 8 Participants |
| Sarcoma Histology Fibroblastic Osteosarcoma | 1 Participants |
| Sarcoma Histology Leiomyosarcoma | 4 Participants |
| Sarcoma Histology Liposarcoma | 6 Participants |
| Sarcoma Histology Not Otherwise Specified | 1 Participants |
| Sarcoma Location Extremity | 13 Participants |
| Sarcoma Location retroperitoneal/pelvis tumors | 6 Participants |
| Sarcoma Location Trunk | 1 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 20 |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 3 / 20 |
Outcome results
Primary
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.
Time frame: 3 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab, Radiation, and Surgery | Objective Response Rate for Neoadjuvant Bevacizumab Combined With Radiation Therapy for Intermediate and High-risk Soft Tissue Sarcomas. | 80-89% necrosis | 2 participants |
| Bevacizumab, Radiation, and Surgery | Objective Response Rate for Neoadjuvant Bevacizumab Combined With Radiation Therapy for Intermediate and High-risk Soft Tissue Sarcomas. | 90-99% necrosis | 4 participants |
| Bevacizumab, Radiation, and Surgery | Objective Response Rate for Neoadjuvant Bevacizumab Combined With Radiation Therapy for Intermediate and High-risk Soft Tissue Sarcomas. | 100% necrosis | 3 participants |
Secondary
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.
Time frame: 3 years
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Bevacizumab, Radiation, and Surgery | Average Change in Blood Flow, Blood Volume,and Permeability Surface Area | 67 Percent Reduction |
p-value: <0.05t-test, 1 sided
Secondary
Change in Median Microvessel Density (MVD) After Bevacizumab Alone
The percentage change in median microvessel density (MVD) after Bevacizumab treatment alone
Time frame: baseline and 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab, Radiation, and Surgery | Change in Median Microvessel Density (MVD) After Bevacizumab Alone | 53 percentage of change in MVD |
p-value: <0.05t-test, 1 sided
Secondary
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.
Time frame: 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab, Radiation, and Surgery | Disease Free Survival | 7 Months |
Secondary
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.
Time frame: 3 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Bevacizumab, Radiation, and Surgery | Distant Recurrence | Distant recurrence | 7 Participants |
| Bevacizumab, Radiation, and Surgery | Distant Recurrence | No distant recurrence | 13 Participants |
Secondary
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.
Time frame: 3 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Bevacizumab, Radiation, and Surgery | Local Control Rate | Local Recurrence | 1 Participants |
| Bevacizumab, Radiation, and Surgery | Local Control Rate | No Local Recurrence | 19 Participants |