Pazopanib in Treating Patients With Recurrent Glioblastoma
Condition: Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Tumor
MeSH terms: Glioblastoma; Gliosarcoma; Recurrence
Intervention: pazopanib hydrochloride; laboratory biomarker analysis
Intervention description: Given orally; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying the side effects and how well pazopanib works in treating
      patients with recurrent glioblastoma. Pazopanib may stop the growth of tumor cells by
      blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor
    

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