Vatalanib in Treating Patients With Recurrent or Progressive Meningioma

Sarcoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00348790
• Other study ID #: NU 05C4
• Secondary ID: STU00005338NU 05
• Status: Completed
• Phase: Phase 2
• Start date: May 2006
• Est. completion date: July 2013

Study information

• Verified date: October 2018
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: July 2013
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Meningioma
• Nervous System Neoplasms
• Sarcoma

Intervention

Drug:
• vatalanib

Locations

Country	Name	City	State
United States	Hematology-Oncology Associates of Illinois	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	Novartis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	MRI with MR Perfusion will be done before treatment and then every 2 months while on study treatment
Other	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	At baseline and then every time an MRI is performed while on study treatment.
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.	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	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
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	Every 2 months for up to 1 year after study treatment.
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	At the end of study treatment
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	Every week while on study treatment until 30 days after last treatment.
Secondary	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.
Secondary	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.