Doxorubicin and Bevacizumab in Treating Patients With Locally Recurrent or Metastatic Soft Tissue Sarcoma

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00052390

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Bevacizumab may stop the growth of tumor cells by stopping blood flow to the tumor. Combining doxorubicin with bevacizumab may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining doxorubicin with bevacizumab in treating patients who have locally recurrent or metastatic soft tissue sarcoma.

Condition or Disease	Intervention/Treatment	Phase
Sarcoma	Biological: bevacizumab Drug: doxorubicin hydrochloride	Phase 2

Detailed Description

OBJECTIVES:

Determine the response rate (partial and complete) in patients with locally recurrent or metastatic soft tissue sarcoma treated with doxorubicin and bevacizumab.
Determine the tolerability of this regimen in these patients.
Determine the toxicity profile of this regimen in these patients.
Determine whether pre-treatment plasma vascular endothelial growth factor level or microvessel density of tumor samples from these patients predicts response to this regimen.

OUTLINE: This is a multicenter study.

Patients receive doxorubicin IV over 5-10 minutes followed by bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with responding disease after reaching the maximum dose of doxorubicin may continue bevacizumab alone.

Patients are followed every 3 months for 1 year.

PROJECTED ACCRUAL: A total of 17-37 patients will be accrued for this study within 13.3 months.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multi-Institutional, Open-Label, Phase II Study Of Doxorubicin And Bevacizumab (Anti-VEFG Monoclonal Antibody, NSC 704865) For Patients With Advanced Or Metastatic Soft-Tissue Sarcoma

Study Start Date :

Oct 1, 2002

Actual Study Completion Date :

Oct 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed soft tissue sarcoma
Locally recurrent or metastatic disease
At least 1 unidimensionally measurable lesion
At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
No prior or concurrent known brain metastases

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

Karnofsky 80-100% OR
ECOG 0-1

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
No bleeding diathesis or coagulopathy

Hepatic

Bilirubin no greater than 1.2 mg/dL
AST and ALT no greater than 2.5 times upper limit of normal
PT and aPTT normal

Renal

Creatinine no greater than 1.5 mg/dL OR
Creatinine clearance at least 60 mL/min
No proteinuria (must be less than 500 mg protein per 24 hours)

Cardiovascular

Cardiac ejection fraction at least 50% by echocardiogram or MUGA
No history of deep vein thrombosis
No clinically significant cardiovascular disease
No uncontrolled hypertension
No myocardial infarction
No unstable angina
No New York Heart Association grade II-IV congestive heart failure
No serious cardiac arrhythmia requiring medication
No grade II or greater peripheral vascular disease within the past year

Pulmonary

No history of pulmonary embolism

Other

No symptomatic peripheral neuropathy grade 2 or greater
No other neoplastic disease within the past 5 years except curatively treated basal cell skin cancer or carcinoma in situ of the cervix
No prior allergic reactions attributed to compounds of similar chemical or biological composition to bevacizumab (including products derived from Chinese hamster ovary cells), doxorubicin, or dexrazoxane
No HIV-positive patients receiving combination antiretroviral therapy
No ongoing or active infection
No psychiatric illness or social situations that would preclude study entry
No other uncontrolled concurrent illness
No serious, non-healing wound ulcer or bone fracture
No significant traumatic injury within the past 3 weeks
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Chemotherapy
At least 4 weeks since prior immunotherapy and recovered
No other concurrent immunotherapy

Chemotherapy

No prior doxorubicin or any other anthracyclines
No more than 1 prior chemotherapy regimen
The following are not considered prior chemotherapy:
Immunotherapy, including cytokines
Peroxisome-proliferator-activated receptor gamma agonists or thalidomide
At least 4 weeks since prior chemotherapy (6 weeks for carmustine or mitomycin) and recovered
No other concurrent chemotherapy

Endocrine therapy

Not specified

Radiotherapy

At least 4 weeks since prior radiotherapy and recovered
No concurrent radiotherapy

Surgery

At least 3 weeks since prior major surgical procedure or open biopsy
At least 1 week since prior needle biopsy

Other

No other concurrent investigational agents
No concurrent full-dose anticoagulants (except to maintain patency of preexisting, permanent indwelling IV catheters) or thrombolytic agent
Concurrent warfarin allowed if INR less than 1.5
No concurrent chronic daily aspirin (more than 325 mg/day) or nonsteroidal anti -inflammatory medications known to inhibit platelet function
No other concurrent investigational or commercial agents or therapies for this malignancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
2	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
3	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112