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A Phase II Trial of GW786034 (Pazopanib) in Patients With Recurrent Glioblastoma

Phase 2
18 Years
Not Enrolling
Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor

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Trial Information

A Phase II Trial of GW786034 (Pazopanib) in Patients With Recurrent Glioblastoma


I. Determine the therapeutic efficacy of pazopanib hydrochloride, as measured by 6-month
progression-free survival (PFS), in patients with recurrent glioblastoma.

II. Determine the safety profile of this drug in these patients.


I. Determine the efficacy of this drug, as measured by radiographic response, time to
progression, and overall survival, in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral pazopanib hydrochloride daily on days 1-28. Treatment repeats every 28
days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for at least 2

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]

- 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

- 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

- 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

- Ergot derivatives (e.g., dihydroergotamine, ergonovine, ergotamine, or

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Howard Fine

Investigator Role:

Principal Investigator

Investigator Affiliation:

North American Brain Tumor Consortium


United States: Food and Drug Administration

Study ID:




Start Date:

May 2007

Completion Date:

Related Keywords:

  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Recurrent Adult Brain Tumor
  • Brain Neoplasms
  • Glioblastoma
  • Gliosarcoma



North American Brain Tumor ConsortiumWatertown, Massachusetts  02472