Vatalanib in Treating Patients With Recurrent or Progressive Meningioma

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase II Trial of PTK-787 in Recurrent or Progressive Meningiomas

Conditions
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Brain and Central Nervous System Tumors, Sarcoma

Intervention / Treatment
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* Drug: vatalanib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vatalanib<br>Patients will be treated with 500 mg of vatalanib, administered orally, twice a day for 28 days (1 cycle). Patients will start at a dose of 250 mg twice a day and increase by 250 mg per day every 7 days until 500 mg twice a day is reached. Patients who are responding may remain on study treatment for 12 months. | Drug: vatalanib<br> <br> * Other names: ZK 222584;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who DID NOT Experience Disease Progression or Death by 6 Months After Starting Treatment. | Patients were assessed with imaging techniques (MRI) during screening/baseline and then every 2 months after starting treatment. Survival status and disease status were recorded. The number of patients who did not experience an event (defined as either death for any reason or progression of their disease) by 6 months after starting treatment were counted. | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine Efficacy (Radiographic and Clinical Improvement) | Efficacy will be assessed by MRI scan and neurological exam upon study entry, every 2 weeks for 2 months, then every 8 weeks while on treatment | At baseline, every 2 weeks for 2 months, then every 8 weeks while on treatment | 
| Best Overall Response Rate (ORR) | Overall Response Rate (ORR) will be as assessed by MRI scan every 2 months while on study treatment and follow-up for up to 1 year after discontinuation of study treatment. The RR is the best response recorded from the start of the treatment until disease progression (PD) where the following definitions apply. Complete Response (CR): Complete disappearance of all measurable and evaluable disease. No new lesions. Partial Response (PR): Greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions. Stable/No Response: Does not qualify for CR, PR, or PD Progressive disease (PD):25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) worsening of evaluable disease, new lesions, clinical worsening OR failure to return for evaluation due to death/deteriorating condition | Every 2 months for up to 1 year after study treatment. | 
| To Correlate the Response Rates With Expression of Certain Types of Genes | Correlation of response rates with the expression of certain types of genes will be assessed by examining tissue samples taken from previous surgery and testing for certain genes | At the end of study treatment | 
| Safety of Vatalanib in Patients With Recurrent of Progressive Meningiomas | Safety of vatalanib will be assessed using National Cancer Institute Common Terminology Criteria of Adverse Events (NCI CTCAE) 3.0 and graded using the following: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Fatal | Every week while on study treatment until 30 days after last treatment. | 
| Number of Months Patients Survive After Being Treatment on the Study. |  | From the date the first patient began treatment until the date the last patient became deceased. | 
| Overall Survival (OS) | Overall Survival will be measured from the first treatment on study until death of any cause. | Every 2 months for up to 1 year after study treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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