Clinical trial NCT00348790: Vatalanib in Treating Patients With Recurrent or Progressive Meningioma
Official title: A Phase II Trial of PTK-787 in Recurrent or Progressive Meningiomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Sarcoma
Keywords: adult grade I meningioma
adult grade II meningioma
adult grade III meningioma
adult malignant hemangiopericytoma
adult anaplastic meningioma
adult papillary meningioma
adult melanocytic lesion
recurrent adult brain tumor
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2006-07-06
Enrollment: 25
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: RATIONALE: Vatalanib may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well vatalanib works in treating patients with recurrent or progressive meningioma.

Detailed description: OBJECTIVES:

Primary

* Determine the efficacy of vatalanib, in terms of radiographic improvement and clinical improvement, in patients with recurrent or progressive meningioma.

Secondary

* Determine the 6-month progression-free survival of these patients.
* Describe the response rate and overall survival of these patients.
* Determine the safety of vatalanib in these patients.
* Correlate the response rates with expression of vascular endothelial growth factor, epidermal growth factor receptor, platelet-derived growth factor, and HER2.
* Develop exploratory data concerning surrogate markers of angiogenic activity in vivo using magnetic resonance perfusion.

OUTLINE: Patients receive oral vatalanib twice daily on days 1-28. Courses repeat every 28 days for 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 1 year.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed meningioma, including the following subtypes:

  * Benign meningioma
  * Malignant meningioma

    * Steroid dosage stable for ≥ 5 days
  * Atypical meningiomas
  * Hemangiopericytoma
* May or may not have neurofibromatosis (NF) type 1 or 2 disease

  * Patients with a history of NF may have other stable CNS tumors, such as schwannoma, acoustic neuroma, or ependymoma only if those lesions have been stable for the past 6 months
* Progressive or recurrent disease by MRI or CT scan

  * Prior radiotherapy allowed provided evidence of disease progression is documented by positron emission tomography, thallium scanning, magnetic resonance spectroscopy, or surgery to rule out radiation necrosis for patients treated with radiosurgery
* Recent resection of recurrent or progressive tumor allowed provided both of the following criteria are met:

  * At least 4 weeks since prior surgery and recovered
  * Evaluable residual disease

PATIENT CHARACTERISTICS:

* Karnofsky performance status 60-100%
* Life expectancy \> 12 weeks
* Absolute neutrophil count ≥ 2,000/mm³
* Platelet count ≥ 100,000/mm³
* Hemoglobin ≥ 10 g/dL (transfusion allowed)
* SGOT and SGPT \< 2 times upper limit of normal (ULN)
* Bilirubin ≤ 1.5 times ULN
* Creatinine \< 1.5 mg/dL
* Negative proteinuria dipstick OR total urinary protein ≤ 500 mg AND creatinine clearance ≥ 50 mL/min
* PT, INR, and PTT ≤ 1.5 times ULN
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for up to 6 months after completion of study treatment
* No history of any other cancer except nonmelanoma skin cancer or carcinoma in situ of the cervix, unless in complete remission and off all therapy for that disease for ≥ 3 years
* No disease that would obscure toxicity or dangerously alter drug metabolism
* No bleeding disorders
* No severe and/or uncontrolled medical conditions that would limit compliance with study requirements, including any of the following:

  * Uncontrolled high blood pressure
  * History of labile hypertension
  * History of poor compliance with an antihypertensive regimen
  * Unstable angina pectoris
  * Symptomatic congestive heart failure
  * Myocardial infarction within the past 6 months
  * Serious uncontrolled cardiac arrhythmia
  * Uncontrolled diabetes
  * Active or uncontrolled infection
  * Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
  * Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of vatalanib (i.e., ulcerative disease, uncontrolled nausea, vomiting, or diarrhea, malabsorption syndrome, bowel obstruction, or inability to swallow tablets)
  * QTc \> 450 (male) or \> 470 (female)
  * Congenital or acquired long QTc syndrome

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* Recovered from prior therapy
* At least 4 weeks since prior radiotherapy, including external-beam radiotherapy, interstitial brachytherapy, or gamma-knife radiosurgery
* At least 4 weeks since prior investigational agents
* More than 4 weeks since prior cytotoxic therapy (6 weeks for nitrosoureas)
* More than 4 weeks since prior immunotherapy
* More than 2 weeks since prior noncytotoxic or biologic therapies
* At least 2 weeks since prior drugs that affect hepatic metabolism (steroids should be tapered off if not clinically indicated)
* At least 2 weeks since prior and no concurrent enzyme-inducing anticonvulsant drugs
* No prior antivascular endothelial growth factor therapy
* No other concurrent investigational agents or anticancer therapy (including chemotherapy, radiotherapy, hormonal therapy, or immunotherapy)
* No concurrent warfarin
* No concurrent grapefruit or grapefruit juice

Primary outcomes:
measure: Number of Patients Who DID NOT Experience Disease Progression or Death by 6 Months After Starting Treatment.
timeFrame: From the date the first patient began treatment until the date the last patient has disease progression, becomes deceased, or completes 6 months of treatment
Secondary outcomes:
measure: Determine Efficacy (Radiographic and Clinical Improvement)
timeFrame: At baseline, every 2 weeks for 2 months, then every 8 weeks while on treatment
measure: Best Overall Response Rate (ORR)
timeFrame: Every 2 months for up to 1 year after study treatment.
measure: To Correlate the Response Rates With Expression of Certain Types of Genes
timeFrame: At the end of study treatment
measure: Safety of Vatalanib in Patients With Recurrent of Progressive Meningiomas
timeFrame: Every week while on study treatment until 30 days after last treatment.
measure: Number of Months Patients Survive After Being Treatment on the Study.
timeFrame: From the date the first patient began treatment until the date the last patient became deceased.
measure: Overall Survival (OS)
timeFrame: Every 2 months for up to 1 year after study treatment.
Other outcomes:
measure: Develop Data Concerning Certain Genes That Cause Tumors to Grow New Blood Vessels
timeFrame: MRI with MR Perfusion will be done before treatment and then every 2 months while on study treatment
measure: To Use the FACT BR Questionnaire to Measure Quality of Life
timeFrame: At baseline and then every time an MRI is performed while on study treatment.
Locations:
city: Chicago
country: United States
facility: Hematology-Oncology Associates of Illinois
state: Illinois
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Seattle
country: United States
facility: University Cancer Center at University of Washington Medical Center
state: Washington
Study officials:
affiliation: Northwestern University
name: Jeffrey J. Raizer, MD
role: PRINCIPAL_INVESTIGATOR
References: