Vatalanib in Treating Patients With Recurrent or Progressive Meningioma

• Sponsor: Northwestern University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00348790
• Collaborator: Novartis (Industry)
• Enrollment: 25
• Locations: 3
• Arm: 1
• Duration (Months): 86
• Patients Per Site: 8.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors; Sarcoma	Drug: vatalanib	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of PTK-787 in Recurrent or Progressive Meningiomas
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Nov 1, 2010
• Actual Study Completion Date: Jul 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: vatalanib; Other Names: PTK787 ZK 222584

Outcome Measures

Primary Outcome Measures

1. 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 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.

Secondary Outcome Measures

1. Determine Efficacy (Radiographic and Clinical Improvement) [At baseline, every 2 weeks for 2 months, then every 8 weeks while on treatment]

   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

2. 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

3. To Correlate the Response Rates With Expression of Certain Types of Genes [At the end of study treatment]

   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

4. Safety of Vatalanib in Patients With Recurrent of Progressive Meningiomas [Every 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

5. 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.]

6. 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.

Other Outcome Measures

1. Develop Data Concerning Certain Genes That Cause Tumors to Grow New Blood Vessels [MRI with MR Perfusion will be done before treatment and then every 2 months while on study treatment]

   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

2. To Use the FACT BR Questionnaire to Measure Quality of Life [At 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hematology-Oncology Associates of Illinois	Chicago	Illinois	United States	60611-2998
2	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
3	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195-6043

Sponsors and Collaborators

• Northwestern University
• Novartis

Investigators

• Principal Investigator: Jeffrey J. Raizer, MD, Northwestern University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jeffrey Raizer, Jeffrey Raizer, MD, Northwestern University
• ClinicalTrials.gov Identifier: NCT00348790
• Other Study ID Numbers: NU 05C4; STU00005338; NU 05C4
• First Posted: Jul 6, 2006
• Last Update Posted: Oct 26, 2018
• Last Verified: Oct 1, 2018

• Keywords provided by Jeffrey Raizer, Jeffrey Raizer, MD, Northwestern University: 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
• Additional relevant MeSH terms: Meningioma; Nervous System Neoplasms; Central Nervous System Neoplasms; Vatalanib

Study Results

Participant Flow

Arm/Group Title	Vatalanib
Arm/Group Description	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.
Period Title: Began Treatment
STARTED	25
COMPLETED	25
NOT COMPLETED	0
Period Title: Began Treatment
STARTED	25
COMPLETED	0
NOT COMPLETED	25

Baseline Characteristics

Arm/Group Title	Vatalanib
Arm/Group Description	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.
Overall Participants	25
Age, Customized (participants) [Number]
21-30	1 4%
31-40	1 4%
41-50	6 24%
51-60	8 32%
61-70 years	8 32%
71-80	0 0%
81-90	1 4%
Sex: Female, Male (Count of Participants)
Female	10 40%
Male	15 60%
Region of Enrollment (participants) [Number]
United States	25 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Who DID NOT Experience Disease Progression or Death by 6 Months After Starting Treatment.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vatalanib
Arm/Group Description	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.
Measure Participants	25
Count of Participants [Participants]	15 60%

2. Secondary Outcome

Title	Determine Efficacy (Radiographic and Clinical Improvement)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Vatalanib
Arm/Group Description	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. vatalanib
Measure Participants	0

3. Secondary Outcome

Title	Best Overall Response Rate (ORR)
Description	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.

Outcome Measure Data

Analysis Population Description

3 patients not evaluable.

Arm/Group Title	Vatalanib
Arm/Group Description	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. vatalanib
Measure Participants	22
SD	15 60%
SD on MRI but clinical decline	2 8%
PD	5 20%

4. Secondary Outcome

Title	To Correlate the Response Rates With Expression of Certain Types of Genes
Description	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

Outcome Measure Data

Analysis Population Description

Data not collected and analyzed.

Arm/Group Title	Vatalanib
Arm/Group Description	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. vatalanib
Measure Participants	0

5. Secondary Outcome

Title	Safety of Vatalanib in Patients With Recurrent of Progressive Meningiomas
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Vatalanib
Arm/Group Description	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. vatalanib
Measure Participants	25
Dehydration	1 4%
Deep vein thrombosis	1 4%
Fatigue	4 16%
Gastrointestinal	1 4%
Hypertension	1 4%
Hyponatremia	1 4%
Leukopenia	1 4%
Pain	1 4%
Rash	1 4%
Transaminase	2 8%
Weight loss	1 4%

6. Secondary Outcome

Title	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vatalanib
Arm/Group Description	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.
Measure Participants	25
Median (95% Confidence Interval) [months]	29.2

7. Secondary Outcome

Title	Overall Survival (OS)
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Vatalanib
Arm/Group Description	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. vatalanib
Measure Participants	21
Median (Full Range) [Months]	26

8. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

Data not collected and analyzed.

Arm/Group Title	Vatalanib
Arm/Group Description	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. vatalanib
Measure Participants	0

9. Other Pre-specified Outcome

Title	To Use the FACT BR Questionnaire to Measure Quality of Life
Description	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.

Outcome Measure Data

Analysis Population Description

Data not collected or analyzed.

Arm/Group Title	Vatalanib
Arm/Group Description	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. vatalanib
Measure Participants	0

Adverse Events

Adverse Event Reporting Description	Patients were assessed for adverse events every 2 weeks for the first 2 months, then every 4 weeks (monthly) while on treatment and up to 30 days after the final dose of study drug.
Arm/Group Title	Vatalanib
Arm/Group Description	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. vatalanib
All Cause Mortality
	Vatalanib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Vatalanib
	Affected / at Risk (%)	# Events
Total	6/25 (24%)
Cardiac disorders
Atrial fibrillation	1/25 (4%)
Ear and labyrinth disorders
Vertigo	1/25 (4%)
Gastrointestinal disorders
Nausea	1/25 (4%)
Metabolism and nutrition disorders
Dehydration	2/25 (8%)
Musculoskeletal and connective tissue disorders
Jaw pain	1/25 (4%)
Nervous system disorders
Headache	1/25 (4%)
Skin and subcutaneous tissue disorders
Rash	1/25 (4%)
Scalp wound	1/25 (4%)
Other (Not Including Serious) Adverse Events
	Vatalanib
	Affected / at Risk (%)	# Events
Total	23/25 (92%)
Blood and lymphatic system disorders
Anemia	2/25 (8%)
Platelets	3/25 (12%)
Cardiac disorders
Hypertension	8/25 (32%)
T wave abnormalities/changes	3/25 (12%)
Sinus tachycardia	2/25 (8%)
Eye disorders
Vision loss	2/25 (8%)
Gastrointestinal disorders
Nausea	6/25 (24%)
Vomiting	6/25 (24%)
Stomatitis	4/25 (16%)
Diarrhea	5/25 (20%)
Dysphagia	2/25 (8%)
Constipation	5/25 (20%)
General disorders
Fatigue	19/25 (76%)
Insomnia	5/25 (20%)
Investigations
Weight loss	3/25 (12%)
Metabolism and nutrition disorders
Transaminase	15/25 (60%)
Alkaline phosphatase	3/25 (12%)
Creatinine	2/25 (8%)
Hyperglycemia	6/25 (24%)
Hypoglycemia	3/25 (12%)
Anorexia	4/25 (16%)
Hypomagnesemia	2/25 (8%)
Dehydration	2/25 (8%)
Hypophosphatemia	3/25 (12%)
Hypokalemia	2/25 (8%)
Hyponatremia	2/25 (8%)
Proteinuria	5/25 (20%)
Musculoskeletal and connective tissue disorders
Pain	6/25 (24%)
Nervous system disorders
Neuropathy: Sensory-facial	4/25 (16%)
Neuropathy - Motor	4/25 (16%)
Headache	12/25 (48%)
Dizziness	2/25 (8%)
Seizure	3/25 (12%)
Memory impairment	2/25 (8%)
Spasm	3/25 (12%)
Confusion	2/25 (8%)
Psychiatric disorders
Depression	2/25 (8%)
Renal and urinary disorders
Hematuria	3/25 (12%)
Skin and subcutaneous tissue disorders
Rash	3/25 (12%)
Vascular disorders
Thrombosis/embolism (vascular access-related)	2/25 (8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.