Gemcitabine and Docetaxel With Bevacizumab in Selected Sarcoma Subtypes
Condition: Sarcoma; Leiomyosarcoma; Malignant Fibrous; Histiocytoma; Angiosarcoma
MeSH terms: Sarcoma; Leiomyosarcoma; Hemangiosarcoma; Histiocytoma
Intervention: gemcitabine; docetaxel; bevacizumab
Intervention MeSH terms: Bevacizumab; Gemcitabine; Docetaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Bevacizumab (avastin); Gemcitabine; Taxotere (docetaxel); 09-015; Soft tissue

Summary:

      The purpose of this study is to test whether an experimental drug called bevacizumab given
      together with gemcitabine and docetaxel, a standard chemotherapy regimen for sarcoma, can
      help sarcoma patients. This trial will examine what effects, good and/or bad the combination
      of gemcitabine, docetaxel and bevacizumab has on sarcoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed unresectable metastatic or locally recurrent leiomyosarcoma,
             Malignant Fibrous Histiocytoma (MFH, also known as high grade Undifferentiated
             Pleomorphic Sarcoma) pleomorphic liposarcoma, rhabdomyosarcoma or angiosarcoma.

          -  Zero to one prior chemotherapy regimens for metastatic disease. Prior adjuvant therapy
             will not count provided it was more than one year previously.

          -  Measurable disease as defined by RECIST

          -  Adequate performance status - ECOG 0 or 1

          -  Patients must be recovered from the toxic effects of prior chemotherapy or radiation.
             Therapy may not start until at least 3 weeks since prior cytotoxic chemotherapy, two
             weeks from completion of radiation therapy, and one week for patients on tyrosine
             kinase inhibitors or other targeted therapy.

          -  Age 18 To 75. As it is quite difficult to administer high dose docetaxel with
             gemcitabine, to the elderly, in order to protect patient safety, we will restrict
             eligibility to patients between the ages of 18 and 75.

          -  Adequate hematologic, hepatic and renal function as defined below

          -  Hemoglobin > or = to 8.0 g/dl

          -  Absolute neutrophil count > or = to 1,500/mm3

          -  Platelet count > or = to 100,000/mm3

          -  Total Bilirubin < or = to1.5 x upper limit of normal (ULN).

          -  ALT (SGOT) or AST (SGPT) < or = to 5 x ULN.

          -  Alkaline Phosphatase < or = to 2.5 x ULN or ≤ 5 x ULN in presence of liver metastases.

          -  Serum creatinine 2.0 mg/dL

          -  Ability to understand informed consent and comply with treatment protocol

          -  Normal cardiac ejection fraction

          -  Urine protein:creatinine (UPC) ratio < than or = to 1.0 at screening

        Exclusion Criteria:

          -  Uncontrolled intercurrent illness including infection or congestive heart failure
             within 6 months.

          -  Prior therapy with gemcitabine, docetaxel or bevacizumab

          -  Patients receiving other investigational agents

          -  Patients with known brain metastases

          -  Pregnancy or unwillingness to use effective birth control

          -  Patients with HIV disease will be permitted, only if they are on effective
             anti-retroviral therapy, have a CD4 count greater than 400, and have had no
             opportunistic infections within the past 6 months.

          -  Patients on anti-coagulation will be permitted if they are on a stable dose of
             warfarin or low-molecular weight heparin, and have had no major bleeds within the past
             6 months.

          -  Inability to comply with study and/or follow-up procedures.

          -  Life expectancy of less than 12 weeks.

          -  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
             bevacizumab cancer study

          -  Active malignancy, other than superficial basal cell and superficial squamous (skin)
             cell, or carcinoma in situ of the cervix within last three years

          -  Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or
             diastolic blood pressure > 100 mmHg lasting > 24 hours on antihypertensive
             medications)

          -  Any prior history of hypertensive crisis or hypertensive encephalopathy

          -  New York Heart Association (NYHA) Grade II or greater congestive heart failure

          -  Significant vascular disease (e.g., aortic aneurysm, aortic dissection), requiring
             surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day
             1

          -  Symptomatic peripheral vascular disease

          -  Evidence of bleeding diathesis or significant coagulopathy (in the absence of
             therapeutic anticoagulation)

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to study enrollment or anticipation of need for major surgical procedure during
             the course of the study

          -  Core biopsy or other minor surgical procedure, excluding placement of a vascular
             access device, within 7 days prior to study enrollment

          -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 6 months prior to study enrollment

          -  Serious, non-healing wound, active ulcer, or non-healing bone fracture

          -  Proteinuria at screening as demonstrated by

          -  Urine protein:creatinine (UPC) ratio > or = to 1.0 at screening (patients discovered
             to have UPC ratio > or = to 1.0 at baseline should undergo a 24 hour urine collection
             and must demonstrate ≤ 1g of protein in 24 hours to be eligible).

          -  Known hypersensitivity to any component of bevacizumab

          -  Pregnant (positive pregnancy test) or lactating. Use of effective means of
             contraception (men and women) in subjects of child-bearing potential

          -  History of hemoptysis (bright red blood of 1/2 teaspoon or more per episode) within 3
             months prior to study enrollment.

          -  Any history of stroke or transient ischemic attack within 6 months

          -  History of myocardial infarction or unstable angina within 6 months