Sarcoma, Soft Tissue Sarcoma
Conditions
Keywords
STS
Brief summary
This research is being done to find out if adding a drug called Avastin to an already approved regimen used for soft-tissue sarcoma, Doxorubicin, will improve overall survival, and slow disease progression. The study will also evaluate the overall safety of combining these drugs. It is not known if combining these drugs will improve outcome. Avastin has been approved for the treatment of metastatic carcinoma of the colon or rectum. It is not approved for the treatment of soft-tissue sarcoma when added to Doxorubicin.
Detailed description
The rationale for this trial is to improve the efficacy of prototypical anti-sarcoma chemotherapeutic regimen Doxorubicin when combined with Avastin®. Soft tissue sarcomas are highly vascular tumors and are therefore ideally suited to trials combining angiogenic inhibitors with chemotherapy. Several studies have revealed correlations between prognosis and surrogates for angiogenesis, including microvessel density, and circulating VEGF and basic fibroblast growth factor (bFGF). The aim of this study is to evaluate the safety and efficacy of Avastin® in combination with Doxorubicin for the treatment of advanced soft-tissue sarcomas.
Interventions
DRUGAvastin
Combination of Avastin and doxorubicin. If initial 90 +/- 15 minute infusion of Avastin is tolerated without fever and chills, the 2nd dose may be infused over 60 +/- 10 minutes. If well tolerated, all subsequent infusions may be delivered over 30 +/- 10 minutes.
DRUGDoxorubicin
The Day 1 6- hour continuous IV infusion must be done through a central venous catheter.
Sponsors
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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
1. Pathologically confirmed intermediate or high grade locally advanced or metastatic soft tissue sarcoma. 2. The presence of measurable disease 3. Normal renal function (spot dipstick \<2\*\* or urine protein: creatinine ratio \>1.0 4. Normal Hepatic function (total bilirubin within JOHC normal limits, transaminases (AST and ALT \<3 times upper limit of normal 5. Hematologic parameters as defined as ANC \>1500/mm³ and Platelets \> 100,000/mm³. 6. Performance status 0-1 on ECOG scale 7. Use of effective means of contraception (men and women) in subjects of child-bearing age 8. No prior use of mesna, adriamycin, ifosfamide or Avastin®. 9. Baseline ECHO or MUGA with LVEF \> or = 50-60%. 10. Age ≥ 18
Exclusion criteria
1. Major surgery within 28 days 2. History of proteinuria \> 1+ 3. Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored Avastin® cancer study 4. Inadequately controlled hypertension (defined as systolic blood pressure \>150 and/or diastolic blood pressure \> 100 mmHg on antihypertensive medications) 5. Any prior history of hypertensive crisis or hypertensive encephalopathy 6. New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E) 7. History of myocardial infarction or unstable angina within 6 months prior to study enrollment 8. History of stroke or transient ischemic attack within 6 months prior to study enrollment 9. Symptomatic peripheral vascular disease 10. Significant vascular disease (e.g., aortic aneurysm, aortic dissection) 11. Evidence of bleeding diathesis or coagulopathy 12. Current or recent (within 10 days of enrollment) use of aspirin (\>325 mg/day) or chronic use of other NSAIDs 13. Current, ongoing treatment with full-dose warfarin or its equivalent (i.e., unfractionated and/or low molecular weight heparin). 14. Known central nervous system or brain metastases 15. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study 16. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment 17. Pregnant (positive pregnancy test) or lactating 18. Proteinuria :creatinine (UPC) ratio ≥ 1.0 at screening or Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible). 19. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0 20. Serious, non-healing wound, ulcer, or bone fracture 21. Known hypersensitivity to any component of Avastin® 22. Inability to comply with study and/or follow-up procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| RECIST | 6 month PFS | Study was terminated because of low accrual. |
Countries
United States
Participant flow
Recruitment details
Only 4 subjects were accrued over 2 years. Study was closed due to slow accrual.
Participants by arm
| Arm | Count |
|---|---|
| Avastin and Doxorubicin Patients will be treated with Avastin 15 mg/kg IV infusion plus doxorubicin 60 mg/M2 (body surface area) IV 6-hour infusion on Day 1 of each 21-day treatment cycle. Dose reductions/modifications will be applied as indicated by toxicities and/or patient tolerance.
Avastin: Combination of Avastin and doxorubicin. If initial 90 +/- 15 minute infusion of Avastin is tolerated without fever and chills, the 2nd dose may be infused over 60 +/- 10 minutes. If well tolerated, all subsequent infusions may be delivered over 30 +/- 10 minutes.
Doxorubicin: The Day 1 6- hour continuous IV infusion must be done through a central venous catheter. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Avastin and Doxorubicin |
|---|---|
| Age, Continuous | 58 years |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 4 |
| serious Total, serious adverse events | 2 / 4 |
Outcome results
Primary
RECIST
Study was terminated because of low accrual.
Time frame: 6 month PFS
Population: study was terminated because of low accrual (4 subjects enrolled/2 years)