Pazopanib Hydrochloride in Treating Young Patients With Solid Tumors That Have Relapsed or Not Responded to Treatment

Inclusion Criteria:

• Diagnosis of 1 of the following:

NOTE: Histologic confirmation not required for intrinsic brain stem cell tumor, optic pathway gliomas, pineal tumors and elevations of cerebrospinal fluid, and serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin.

• Histologically confirmed relapsed or refractory solid tumors at original diagnosis including CNS tumors* (Part 1 and Part 2a)

  • Neurologic deficits in patients with CNS tumors must have been relatively stable for ≥ 1 week

• Histologically confirmed soft tissue sarcoma, desmoplastic small round cell tumor, or extraosseus Ewing sarcoma at original diagnosis including the following (Part 2b):

  • Tumor in the head, neck, or extremity or fixed within the abdomen or pelvis that it is not sensitive to motion artifact

  • No isolated pulmonary metastases

    • Disease with no known curative therapy or no therapy proven to prolong survival with acceptable quality of life
    • Measurable or evaluable disease (Part 1 and Part 2a)
    • Measurable tumor that is ≥ 2 cm in its longest diameter (Part 2b)
    • Patients must be:
• > 2 years of age and ≤ 21 years of age (Part 1 and Part 2a)

• > 2 years of age and ≤ 25 years of age (Part 2b)

  • Body surface area ≥ 0.48 m^2 (Part 1 and Part 2b)
  • For patients with CNS tumors or CNS metastasis, there must be no evidence of new CNS hemorrhage of more than punctate size and/or > 3 foci of punctate hemorrhage on baseline MRI for primary CNS tumors ≥ 14 days prior to study entry
  • Karnofsky performance status (PS) 50-100% (> 16 years of age)
  • Lansky PS 50-100% (≤ 16 years of age)
  • Platelet count ≥ 100,000/mm^3 (transfusion independent)
  • ANC ≥ 1,000/mm^3
  • Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)
  • Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age/gender as follows:
• 0.6 mg/dL (1 to < 2 years of age)
• 0.8 mg/dL (2 to < 6 years of age)
• 1 mg/dL (6 to < 10 years of age)
• 1.2 mg/dL (10 to < 13 years of age)
• 1.5 mg/dL (male ) or 1.4 mg/dL (female) (13 to < 16 years of age)

• 1.7 mg/dL (male) or 1.4 mg/dL (female) ( ≥ 16 years of age)

  • Urine protein:creatinine ratio < 1 OR urinalysis negative for protein OR 24-hour urine protein level < 1 g
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT ≤ 110 U/L
  • PT and PTT ≤ 1.2 times ULN
  • INR ≤ 1.2
  • Serum albumin ≥ 2 g/dL
  • No grade > 1 abnormalities of potassium, calcium, magnesium, or phosphorous

• Supplementation allowed

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

• Oral contraceptives are not considered effective

  • Adequate cardiac function defined as any of the following:
• Shortening fraction of ≥ 27% by echocardiogram
• Ejection fraction of ≥ 50% by gated radionuclide study
• QTc < 450 msec

• No history of myocardial infarction, severe or unstable angina, or peripheral vascular disease or familial QTc prolongation

  • Adequate blood pressure defined as ≤ 95th percentile for age, height, and gender
  • Known history of well-controlled seizures allowed
  • Able to swallow whole tablets (Part 1 and Part 2b)
  • No uncontrolled infection
  • No evidence of active bleeding, intratumoral hemorrhage, or bleeding diathesis
  • None of the following conditions within the past 6 months:
• Arterial thromboembolic events, including transient ischemic attack or cerebrovascular accident
• Pulmonary embolism
• Deep vein thrombosis

• Other venous thromboembolic event

  • No hemoptysis within the past 6 weeks
  • No serious or non-healing wound, ulcer, or bone fracture
  • No significant traumatic injury within the past 28 days
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • No patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
  • No fine-needle aspiration within 48 hours before day 1 of therapy
  • Fully recovered from all prior therapy (e.g., chemotherapy, immunotherapy, or radiotherapy)
  • At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for prior nitrosourea)
  • At least 7 days since prior hematopoietic growth factor
  • At least 21 days since prior VEGF-Trap
  • No prior pazopanib hydrochloride
  • At least 7 days since prior VEGF-blocking tyrosine kinase inhibitor or other biological agents
  • At least 3 half-lives since prior monoclonal antibody, including bevacizumab
  • At least 21 days since any other prior anticancer antibody therapy
  • At least 2 weeks since prior local palliative radiotherapy (small port)
  • At least 3 months since prior total-body irradiation, craniospinal radiotherapy, or ≥ 50% radiotherapy to the pelvis
  • At least 6 weeks since prior other substantial bone marrow radiotherapy
  • At least 2 months since stem cell transplantation and no evidence of graft-vs-host disease
  • Thyroid replacement therapy allowed provided a stable dose has been received for ≥ 4 weeks
  • No concurrent medication for cardiac function or hypertension
  • Concurrent corticosteroids allowed provided dose is stable or decreasing for > 7 days (for patients enrolled in Part 1 and Part 2a of study)

• No concurrent corticosteroids for patients enrolled in Part 2b of the study

  • No other concurrent anticancer agents or radiotherapy
  • No other concurrent investigational drugs
  • No concurrent enzyme-inducing anticonvulsants
  • No concurrent anticoagulation therapy with coumadin and/or low molecular weight heparin

• Prophylactic anticoagulation therapy (i.e., intraluminal heparin) of venous or arterial access devices allowed

  • No concurrent aspirin, ibuprofen, or other NSAIDs
  • No concurrent drugs metabolized through several of the specific P450 cytochrome isoform including inducers or inhibitors of CYP3A4
  • No concurrent drugs with a known risk of torsades de pointes
  • At least 28 days since prior major surgical procedure, laparoscopic procedure, or open biopsy

• Port placement or central line placement 48 hours before day 1 of therapy allowed

  • No core biopsy within the past 7 days