Phase II Study of Doxorubicin and Avastin® in Sarcoma.

NCT ID: NCT00755261

Last Updated: 2015-05-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2010-11-30

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.

Conditions

Sarcoma; Soft Tissue Sarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Avastin

Intervention Type: DRUG

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

Intervention Type: DRUG

The Day 1 6- hour continuous IV infusion must be done through a central venous catheter.

Interventions

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.

Intervention Type: DRUG

Doxorubicin

The Day 1 6- hour continuous IV infusion must be done through a central venous catheter.

Intervention Type: DRUG

Other Intervention Names

bevacizumab; Adriamycin

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Katherine A Thornton, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins SKCCC

Locations

Johns Hopkins SKCCC

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

NA_00013238

Identifier Type: OTHER

Identifier Source: secondary_id

AVF3855s

Identifier Type: OTHER

Identifier Source: secondary_id

J07133

Identifier Type: -

Identifier Source: org_study_id