Sunitinib in Sarcomas of the Central Nervous System
Condition: Gliosarcoma; Central Nervous System Sarcoma
MeSH terms: Sarcoma; Gliosarcoma
Intervention: Sunitinib; wGT3x-BT
Intervention description: Sunitinib will be administered at a dose of 50 mg daily for 2 consecutive weeks followed by 1 week of rest until there is disease progression or development of intolerable side effects.; Participants will given a small, portable pager-type and watch accelerometers to wear at the hip or non-dominant wrist. Worn daily for 6 cycles
Intervention MeSH terms: Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Gliosarcoma; Brain Tumor; MDASI

Summary:

      Background:

      A sarcoma is a rare cancer. It grows in the body's connective tissue. Sarcomas in the brain
      and central nervous system are especially rare. The drug Sunitinib has been approved in many
      countries for treating other types of rare or advanced cancers. These include kidney,
      pancreas, and bowel cancer. Researchers want to see if it can help people with sarcomas of
      the central nervous system.

      Objective:

      To study the effects of Sunitinib on gliosarcomas or sarcomas of the central nervous system.

      Eligibility:

      Adults ages 18 and older with a gliosarcoma or sarcoma of the central nervous system

      Design:

      Participants will be screened with the following tests. Some may be done as part of their
      regular cancer care:

      Medical history

      Medication review

      Physical exam

      Blood, heart, and pregnancy tests

      Cranial scans to locate and measure their tumor

      Participants will take Sunitinib by mouth every day for 2 weeks and then take none of the
      drug for 1 week. These 3 weeks equal 1 cycle.

      Participants will have 2 study visits in cycle 1. They will have 1 visit in all other cycles.
      They will answer questions about quality of life and repeat some screening tests.

      Participants will take their blood pressure at home weekly. They keep a diary of each dose of
      Sunitinib and blood pressure reading.

      Participants can choose to share data about their physical activity levels and quality of
      sleep. These participants will wear a small, portable watch-sized accelerometer device on the
      wrist for 6 cycles.

      About 1 month after their last study drug dose, participants will have a final study visit.
      They will have a physical exam, blood tests, and scans.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Patients must have histologically confirmed gliosarcoma (primary or secondary) or
             primary central nervous system sarcoma confirmed by the Laboratory of Pathology,
             National Cancer Institute (NCI).

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured bi-dimensionally by MRI (or computed tomography (CT) scan if
             magnetic resonance imaging (MRI) is contraindicated).

          -  Patients must have failed standard therapy consisting of surgery, irradiation, and
             chemotherapy if indicated.

          -  Age greater than or equal to 18 years.

          -  Karnofsky greater than or equal to 60%.

          -  Patients must have normal organ and marrow function as defined below:

               -  leukocytes greater than or equal to 3,000/mcL

               -  absolute neutrophil count greater than or equal to 1,500/mcL

               -  platelets greater than or equal to 100,000/mcL

               -  total bilirubin within normal institutional limits

               -  Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase
                  (SGOT)/Alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT)
                  less than or equal to 2.5 times institutional upper limit of normal

               -  creatinine within normal institutional limits OR creatinine clearance greater
                  than or equal to 60 mL/min/1.73 m(2) for patients with

        creatinine levels above institutional normal.

          -  Patients must have the ability to understand and the willingness to sign a written
             informed consent document indicating that they are aware of the investigational nature
             of this study.

          -  The effects of sunitinib on the developing human fetus are unknown. For this reason
             and because anti-angiogenic agents are known to be teratogenic, women of child-bearing
             potential and men must agree to use adequate contraception (hormonal or barrier method
             of birth control; abstinence) prior to study entry and for the duration of study
             participation. Should a woman become pregnant or suspect she is pregnant while she or
             her partner is participating in this study, she should inform her treating physician
             immediately.

          -  Tumor tissue blocks or at least 10-15 unstained slides from the diagnosis should be
             available.

          -  At the time of registration, all subjects must be removed greater than or equal to 28
             days from any investigational agents.

        EXCLUSION CRITERIA:

          -  Patients who are receiving any other investigational agents.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Prior use of tyrosine kinase inhibitors or vascular endothelial growth factor (VEGF)
             inhibition.

          -  Patients who are receiving strong cytochromes P450 (CYP450) inducers or inhibitors are
             ineligible.

          -  Pregnant women are excluded from this study because sunitinib has potential for
             teratogenic or abortifacient effects. Because there is an unknown but potential risk
             for adverse events in nursing infants secondary to treatment of the mother with
             sunitinib, breastfeeding should be discontinued if the mother is treated with
             sunitinib.

          -  Patients with known human immunodeficiency virus (HIV) history on combination
             antiretroviral therapy are ineligible because of the potential for pharmacokinetic
             interactions with sunitinib. In addition, these patients are at increased risk of
             lethal infections when treated with marrow-suppressive therapy.

          -  Uncontrolled hypertension (> 150/100 mm hemoglobin (Hg) while on antihypertensive
             medications.

          -  New York Heart Association class II or greater congestive heart failure.

          -  Serious cardiac arrhythmia requiring medication.

          -  Baseline echocardiogram with ejection fraction < 50% or greater than or equal to 20%
             decrease from a prior study.

          -  Corrected QT interval (QTc) > 500 msec on baseline electrocardiogram (EKG)

          -  Patients who require use of therapeutic doses of coumarin-derivative anticoagulants
             such as warfarin are excluded, although doses of up to 2 mg daily are permitted for
             prophylaxis of thrombosis. Note: Low molecular weight heparin is permitted provided
             the patient's international normalized ratio (INR) is less than or equal to 1.5.

          -  Previous exposure to anthracyclines.