Pazopanib in Treating Patients With Recurrent Glioblastoma

Adult Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00459381
• Other study ID #: NCI-2012-02710
• Secondary ID: NABTC-0602U01CA0
• Status: Completed
• Phase: Phase 2
• First received: April 9, 2007
• Last updated: February 1, 2013
• Start date: May 2007

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

Description:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• pazopanib hydrochloride
Given orally

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	North American Brain Tumor Consortium	Watertown	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival		6 months	No
Secondary	Toxicity evaluated according to the NCI Common Toxicity Criteria (CTCAE) version 3.0		Up to 2 years	Yes
Secondary	Time to treatment failure		From date of registration to the date of first observation of progressive disease, non-reversible neurologic progression or permanently increased steroid requirement, death due to any cause, or early discontinuation of treatment, assessed up to 2 years	No
Secondary	Overall survival		From date of registration to date of death due to any cause, assessed up to 2 years	No