Skip to content

Vatalanib in Treating Patients With Recurrent or Progressive Meningioma

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

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00348790
Enrollment
25
Registered
2006-07-06
Start date
2006-05-31
Completion date
2013-07-31
Last updated
2018-10-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

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

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.

Interventions

Sponsors

Novartis
CollaboratorINDUSTRY
Northwestern University
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion 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

Design outcomes

Primary

MeasureTime frameDescription
Number of Patients Who DID NOT Experience Disease Progression or Death by 6 Months After Starting Treatment.From the date the first patient began treatment until the date the last patient has disease progression, becomes deceased, or completes 6 months of treatmentPatients 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.

Secondary

MeasureTime frameDescription
Determine Efficacy (Radiographic and Clinical Improvement)At baseline, every 2 weeks for 2 months, then every 8 weeks while on treatmentEfficacy 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
Best Overall Response Rate (ORR)Every 2 months for up to 1 year after study treatment.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
To Correlate the Response Rates With Expression of Certain Types of GenesAt the end of study treatmentCorrelation 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
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)Every 2 months for up to 1 year after study treatment.Overall Survival will be measured from the first treatment on study until death of any cause.
Safety of Vatalanib in Patients With Recurrent of Progressive MeningiomasEvery week while on study treatment until 30 days after last treatment.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

Other

MeasureTime frameDescription
Develop Data Concerning Certain Genes That Cause Tumors to Grow New Blood VesselsMRI with MR Perfusion will be done before treatment and then every 2 months while on study treatmentData concerning certain genes that cause tumors to grow new blood vessels will be examined by MRI scan with MR Perfusion done before treatment and then every 2 months while on study treatment
To Use the FACT BR Questionnaire to Measure Quality of LifeAt baseline and then every time an MRI is performed while on study treatment.FACT BR questionnaire will be used to measure quality of life at baseline and then every time an MRI scan is performed while on study treatment

Countries

United States

Participant flow

Participants by arm

ArmCount
Vatalanib
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.
25
Total25

Withdrawals & dropouts

PeriodReasonFG000
Completed TreatmentAdverse Event4
Completed TreatmentDisease progression14
Completed TreatmentRequired surgery2
Completed TreatmentUnable to travel to study site1
Completed TreatmentWithdrawal by Subject4

Baseline characteristics

CharacteristicVatalanib
Age, Customized
21-30
1 participants
Age, Customized
31-40
1 participants
Age, Customized
41-50
6 participants
Age, Customized
51-60
8 participants
Age, Customized
61-70 years
8 participants
Age, Customized
71-80
0 participants
Age, Customized
81-90
1 participants
Region of Enrollment
United States
25 participants
Sex: Female, Male
Female
10 Participants
Sex: Female, Male
Male
15 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
23 / 25
serious
Total, serious adverse events
6 / 25

Outcome results

Primary

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.

Time frame: 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

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
VatalanibNumber of Patients Who DID NOT Experience Disease Progression or Death by 6 Months After Starting Treatment.15 Participants
Secondary

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

Time frame: Every 2 months for up to 1 year after study treatment.

Population: 3 patients not evaluable.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
VatalanibBest Overall Response Rate (ORR)SD15 Participants
VatalanibBest Overall Response Rate (ORR)SD on MRI but clinical decline2 Participants
VatalanibBest Overall Response Rate (ORR)PD5 Participants
Secondary

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

Time frame: At baseline, every 2 weeks for 2 months, then every 8 weeks while on treatment

Population: Data not collected. Statistical design of study was based on participation of patients with WHO grade I meningioma. Most patients enrolled in the study were WHO grade II and WHO grade III.

Secondary

Number of Months Patients Survive After Being Treatment on the Study.

Time frame: From the date the first patient began treatment until the date the last patient became deceased.

ArmMeasureValue (MEDIAN)
VatalanibNumber of Months Patients Survive After Being Treatment on the Study.29.2 months
Secondary

Overall Survival (OS)

Overall Survival will be measured from the first treatment on study until death of any cause.

Time frame: Every 2 months for up to 1 year after study treatment.

Population: Number of patients with WHO grade II or WHO grade III meningioma.

ArmMeasureValue (MEDIAN)
VatalanibOverall Survival (OS)26 Months
Secondary

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

Time frame: Every week while on study treatment until 30 days after last treatment.

Population: Toxicities determined to be either grade 3 or grade 4 and at least possibly related to study drug are reported here.

ArmMeasureGroupValue (NUMBER)
VatalanibSafety of Vatalanib in Patients With Recurrent of Progressive MeningiomasPain1 participants
VatalanibSafety of Vatalanib in Patients With Recurrent of Progressive MeningiomasDehydration1 participants
VatalanibSafety of Vatalanib in Patients With Recurrent of Progressive MeningiomasDeep vein thrombosis1 participants
VatalanibSafety of Vatalanib in Patients With Recurrent of Progressive MeningiomasFatigue4 participants
VatalanibSafety of Vatalanib in Patients With Recurrent of Progressive MeningiomasGastrointestinal1 participants
VatalanibSafety of Vatalanib in Patients With Recurrent of Progressive MeningiomasHypertension1 participants
VatalanibSafety of Vatalanib in Patients With Recurrent of Progressive MeningiomasHyponatremia1 participants
VatalanibSafety of Vatalanib in Patients With Recurrent of Progressive MeningiomasLeukopenia1 participants
VatalanibSafety of Vatalanib in Patients With Recurrent of Progressive MeningiomasRash1 participants
VatalanibSafety of Vatalanib in Patients With Recurrent of Progressive MeningiomasTransaminase2 participants
VatalanibSafety of Vatalanib in Patients With Recurrent of Progressive MeningiomasWeight loss1 participants
Secondary

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

Time frame: At the end of study treatment

Population: Data not collected and analyzed.

Other Pre-specified

Develop Data Concerning Certain Genes That Cause Tumors to Grow New Blood Vessels

Data concerning certain genes that cause tumors to grow new blood vessels will be examined by MRI scan with MR Perfusion done before treatment and then every 2 months while on study treatment

Time frame: MRI with MR Perfusion will be done before treatment and then every 2 months while on study treatment

Population: Data not collected and analyzed.

Other Pre-specified

To Use the FACT BR Questionnaire to Measure Quality of Life

FACT BR questionnaire will be used to measure quality of life at baseline and then every time an MRI scan is performed while on study treatment

Time frame: At baseline and then every time an MRI is performed while on study treatment.

Population: Data not collected or analyzed.

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026