Intervention: Pazopanib Hydrochloride
Trial phase: Phase 2
SMILES: Cc1ccc(Nc2nccc(N(C)c3ccc4c(C)n(C)nc4c3)n2)cc1S(N)(=O)=O.Cl
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 35
Group description: Patients receive oral pazopanib hydrochloride daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Other: laboratory biomarker analysis

pazopanib hydrochloride: Given orally

laboratory biomarker analysis: Correlative studies
Eligibility criteria:
Inclusion Criteria:

Histologically confirmed glioblastoma multiforme, including gliosarcoma

Recurrent disease

Must have unequivocal radiographic evidence of tumor progression by MRI, as defined by any of the following:

25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline
Clear worsening of any evaluable disease
Appearance of any new lesions or site
Clear clinical worsening
Must have failed prior radiotherapy that was completed ≥ 42 days ago
Patients who received prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease, rather than radiation necrosis, based on positron emission tomography (PET) scan, thallium scanning, magnetic resonance spectroscopy, or surgical documentation of disease

Treatment for no more than 2 prior relapses allowed

Relapse is defined as progression following initial therapy (i.e., radiotherapy with or without chemotherapy, if that was used as initial therapy; therefore no more than 3 prior therapies [initial therapy and therapy for 2 relapses] allowed)

If the patient had a surgical resection for relapsed disease and no anticancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered as 1 relapse
For patients who had prior therapy for a low-grade glioma, the surgical diagnosis of a glioblastoma multiforme will be considered the first relapse
Karnofsky performance status 60-100%
Life expectancy > 8 weeks
WBC ≥ 3,000/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
Hemoglobin ≥ 10 g/dL (may be reached by transfusion)
Platelet count ≥ 100,000/mm^3
PT/INR/PTT ≤ 1.2 times upper limit of normal (ULN)
SGOT < 2.5 times ULN
Bilirubin < 2.5 times ULN
Creatinine < 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min
Urine protein:creatinine ratio > 1 OR urine protein < 1,000 mg by 24-hour urine collection OR proteinuria < 1+
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective double-barrier contraception during study therapy OR practice abstinence from sexual intercourse for 14 days prior to, during, and for ≥ 21 days after study therapy

Systolic blood pressure (BP) ≤ 140 mm Hg and diastolic BP ≤ 90 mm Hg

Prior initiation or adjustment of BP medication allowed provided the average of 3 BP readings is ≤ 140/90 mm Hg
No uncontrolled significant medical illnesses that would preclude study therapy

No other conditions, including any of the following:

Serious or nonhealing wound, ulcer, or bone fracture
Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
Cerebrovascular accident (CVA) within the past 6 months
Myocardial infarction, cardiac arrhythmia, admission for unstable angina, cardiac angioplasty, or stenting within the past 84 days
Venous thrombosis within the past 84 days

New York Heart Association (NYHA) class III or IV heart failure

Asymptomatic NYHA class II heart failure while on treatment allowed
No other cancer except for nonmelanoma skin cancer or carcinoma in situ of the cervix unless in complete remission and off of all therapy for that disease for ≥ 3 years
No disease that would obscure toxicity or dangerously alter drug metabolism
No history of allergic reactions attributed to compounds of similar chemical or biological composition to pazopanib hydrochloride or other agents
No QTc prolongation (i.e., QTc interval ≥ 500 msecs) or other significant ECG abnormalities

No condition that impairs the ability to swallow and retain pazopanib hydrochloride, including any of the following:

Gastrointestinal tract disease resulting in an inability to take oral medication
Requirement for IV alimentation
Prior surgical procedures affecting absorption
Active peptic ulcer disease
See Disease Characteristics
Recovered from prior therapy

At least 28 days since prior resection of recurrent or progressive tumor and recovered

Residual disease after resection of recurrent glioblastoma is not mandated for eligibility into the study

More than 7 days since prior noncytotoxic agents (e.g., interferon, tamoxifen, thalidomide, or isotretinoin)

Radiosensitizers allowed
More than 14 days since prior investigational agents
More than 14 days since prior vincristine
More than 21 days since prior procarbazine
More than 28 days since prior cytotoxic therapy
More than 42 days since prior nitrosoureas
No prior bevacizumab
No prior sorafenib tosylate or sunitinib malate
No prior pazopanib hydrochloride

No concurrent CYP2C9 substrates, including any of the following:

Anticoagulants (e.g., warfarin [therapeutic doses only])
Oral hypoglycemics (e.g., glipizide, glyburide, tolbutamide, glimepiride, or nateglinide)
Ergot derivatives (e.g., dihydroergotamine, ergonovine, ergotamine, or methylergonovine)
Neuroleptics (e.g., pimozide)
Erectile dysfunction agents (e.g., sildenafil, tadalafil, or vardenafil)
Antiarrhythmics (e.g., bepridil, flecainide, lidocaine, mexilitine, amiodarone, quinidine, or propafenone)
Immune modulators (e.g., cyclosporine, tacrolimus, or sirolimus)
Miscellaneous drugs (e.g., theophylline, quetiapine, risperidone, tacrine, clozapine, or atomoxetine)
No concurrent combination antiretroviral therapy for HIV-positive patients
No other concurrent anticancer therapy (including chemotherapy, radiotherapy, hormonal treatment, or immunotherapy) or investigational drugs

No concurrent enzyme-inducing anti-epileptic drugs (EIAEDs)

Non-EIAEDs allowed