Phase II Study of Doxorubicin and Avastin® in Sarcoma.

Phase II Study of Doxorubicin and Avastin® for Patients With Advanced Soft-tissue Sarcomas.

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.

Study Overview

• Status: Terminated
• Conditions: Sarcoma; Soft Tissue Sarcoma
• Intervention / Treatment: Drug: Avastin; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins SKCCC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: 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.; Other Names: bevacizumab; Drug: Doxorubicin; The Day 1 6- hour continuous IV infusion must be done through a central venous catheter.; Other Names: Adriamycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RECIST	Study was terminated because of low accrual.	6 month PFS

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Investigators: Principal Investigator: Katherine A Thornton, MD, Johns Hopkins SKCCC

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: September 17, 2008
• First Submitted That Met QC Criteria: September 17, 2008
• First Posted (Estimate): September 18, 2008

Study Record Updates

• Last Update Posted (Estimate): May 8, 2015
• Last Update Submitted That Met QC Criteria: May 7, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: STS
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antibiotics, Antineoplastic; Bevacizumab; Doxorubicin
• Other Study ID Numbers: J07133; NA_00013238 (Other Identifier: Johns Hopkins University IRB); AVF3855s (Other Identifier: Genentech, Inc)