Clinical trial NCT00459381: Pazopanib in Treating Patients With Recurrent Glioblastoma
Official title: A Phase II Trial of GW786034 (Pazopanib) in Patients With Recurrent Glioblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Recurrent Adult Brain Tumor
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-04-11
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 6 Months Progression-free Survival
timeFrame: 6 months
measure: Number of Participants Discontinuing Treatment Due to Toxicity
timeFrame: 2 years
Secondary outcomes:
measure: Most Common Toxicities Experienced After at Least One Dose of Pazopanib
timeFrame: Up to 2 years
measure: Overall Radiographic Response (ORR) Rate
timeFrame: 2 years
measure: Best Radiographic Response
timeFrame: 3 years
measure: Overall Survival
timeFrame: From date of registration to date of death due to any cause, assessed up to 2 years
measure: Time to Progression or Progression Free Survival
timeFrame: 1 year
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Bethesda
country: United States
facility: National Cancer Institute Neuro-Oncology Branch
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: North American Brain Tumor Consortium
name: Howard Fine, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.