Pazopanib in Treating Patients With Recurrent Glioblastoma

NCT ID: NCT00459381

Last Updated: 2017-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2008-12-31

Brief 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

Detailed 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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (pazopanib hydrochloride)

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

Group Type: EXPERIMENTAL

pazopanib hydrochloride

Intervention Type: DRUG

Given orally

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

pazopanib hydrochloride

Given orally

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

GW786034B; Votrient

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Howard Fine, MD

Role: PRINCIPAL_INVESTIGATOR

North American Brain Tumor Consortium

Locations

University of California Los Angeles

Los Angeles, California, United States

University of California San Francisco

San Francisco, California, United States

National Cancer Institute Neuro-Oncology Branch

Bethesda, Maryland, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Duke University

Durham, North Carolina, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

MD Anderson Cancer Center

Houston, Texas, United States

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

References

Iwamoto FM, Lamborn KR, Robins HI, Mehta MP, Chang SM, Butowski NA, Deangelis LM, Abrey LE, Zhang WT, Prados MD, Fine HA. Phase II trial of pazopanib (GW786034), an oral multi-targeted angiogenesis inhibitor, for adults with recurrent glioblastoma (North American Brain Tumor Consortium Study 06-02). Neuro Oncol. 2010 Aug;12(8):855-61. doi: 10.1093/neuonc/noq025. Epub 2010 Mar 3.

Reference Type: DERIVED

PMID: 20200024 (View on PubMed)

Other Identifiers

NABTC-0602

Identifier Type: -

Identifier Source: secondary_id

U01CA062399

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000538083

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02710

Identifier Type: -

Identifier Source: org_study_id