Imatinib Mesylate and Hydroxyurea in Treating Patients With Recurrent or Progressive Meningioma

Glioblastoma Clinical Trial

Official title:

A Phase II Study of Imatinib Mesylate Plus Hydroxyurea in the Treatment of Patients With Recurrent/Progressive Meningioma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00354913
• Other study ID #: Pro00006768
• Secondary ID: DUMC-7082-05-4R0
• Status: Completed
• Phase: Phase 2
• First received: July 19, 2006
• Last updated: January 14, 2013
• Start date: May 2005
• Est. completion date: October 2010

Study information

• Verified date: December 2012
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as hydroxyurea, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving imatinib mesylate together with hydroxyurea may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving imatinib mesylate together with hydroxyurea works in treating patients with recurrent or progressive meningioma.

Description:

OBJECTIVES:

Primary

• Evaluate the activity of imatinib mesylate and hydroxyurea, as measured by 6-month progression-free survival, in patients with recurrent or progressive meningioma.

Secondary

• Evaluate the progression-free survival (PFS)

• Overall survival (OS),

• Objective response rate among patients treated with this regimen.

OUTLINE: This is an open-label study.

Patients receive oral imatinib mesylate once or twice daily and oral hydroxyurea twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 21 patients will be accrued for this study.

Other known NCT identifiers

• NCT00611234

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: October 2010
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed meningioma

• Recurrent or progressive disease after prior surgical resection

• Measurable disease by contrast-enhanced MRI

• Multifocal disease allowed

• No evidence of intratumor hemorrhage on pretreatment diagnostic imaging

• Stable postoperative grade 1 hemorrhage allowed

• No peripheral edema or central or systemic fluid collections = grade 2 (e.g., pericardial effusion, pulmonary effusion, ascites)

PATIENT CHARACTERISTICS:

• Karnofsky performance status 70-100%

• Absolute neutrophil count > 1,500/mm³

• Hemoglobin > 9 g/dL

• Platelet count > 100,000/mm³

• Potassium normal*

• Calcium normal*

• Magnesium normal*

• Phosphorus normal*

• alanine aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 times upper limit of normal (ULN)

• Bilirubin < 1.5 times ULN

• Creatinine < 1.5 times ULN OR creatinine clearance > 50 mL/min

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No excessive risk of bleeding, as defined by stroke within the past 6 months

• No active systemic bleeding (i.e., gastrointestinal bleeding or gross hematuria)

• No history of central nervous system (CNS) or intraocular bleeding or septic endocarditis

• No concurrent severe and/or uncontrolled medical disease, including any of the following:

• Uncontrolled diabetes

• Congestive cardiac failure

• Myocardial infarction within the past 6 months

• Poorly controlled hypertension

• History of labile hypertension

• History of poor compliance with antihypertensive regimen

• Chronic renal disease

• Active uncontrolled infection requiring intravenous antibiotics

• No acute or chronic liver disease (i.e., hepatitis, cirrhosis)

• No HIV positivity

• No impairment of gastrointestinal function or disease that may significantly alter the absorption of imatinib mesylate, including any of the following:

• Ulcerative disease

• Uncontrolled nausea

• Vomiting

• Diarrhea

• Malabsorption syndrome

• Bowel obstruction

• Inability to swallow tablets

• No other malignancy within the past 5 years except basal cell skin cancer or cervical carcinoma in situ NOTE: *Unless correctable with supplements

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered from prior therapy

• More than 1 week since prior tumor biopsy

• More than 2 weeks since prior surgical resection

• Prior hydroxyurea allowed provided patient has not had progressive disease or toxicity > grade 3

• No prior imatinib mesylate or other platelet-derived growth factor-directed therapy

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)*

• Chemotherapeutic agents such as etoposide that are normally given at shorter intervals allowed even if < 4 weeks from last prior dose of chemotherapy

• At least 4 weeks since prior radiotherapy*

• At least 1 week since prior biological, immunotherapeutic, or cytostatic drugs

• At least 2 weeks since prior investigational drugs

• No concurrent warfarin NOTE: *Unless there is unequivocal evidence of tumor progression

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioblastoma
• Gliosarcoma
• Meningioma

Intervention

Drug:
• hydroxyurea
Hydroxyurea is administered orally twice a day. The dose will be set at 500 mg twice a day for all patients. If vomiting occurs not additional trial medication should be taken that day in an effort to replace the material that has been vomited. It is recommended that patients take their prescribed hydroxyurea at the same time that they take their prescribed imatinib mesylate, however, a 30-60 minute interval between agents is acceptable, if required for practical or other compliance issues.
• imatinib mesylate
Imatinib administered orally on daily, continuous basis. Imatinib doses of 400mg/600mg administered once daily, whereas daily doses of 800mg/greater administered as equally divided dose taken twice day. Dose for Imatinib: Patients receiving p450-inducing antiepileptic drugs:500mg twice day Patients not receiving p450-inducing antiepileptic drugs:400mg/day. If patients who were not on Cytochrome P450, family 3, subfamily A (CYP3A) enzyme-reducing anti-epileptic drug (EIAED) when originally enrolled must initiate CYP3A enzyme-inducing anti-epileptic drug while on study, study regimen will remain same for minimum of 2 wks before pt transitions to dosing as specified for patients on anti-epileptic drug. If patients originally enrolled must discontinue all EIAEDs while on study, in interest of patient safety, dosing of study regimen will transition to that of patients not on anti-epileptics immediately.

Locations

Country	Name	City	State
United States	Duke Cancer Institute	Durham	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Duke University	National Cancer Institute (NCI), Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (1)

Reardon DA, Norden AD, Desjardins A, Vredenburgh JJ, Herndon JE 2nd, Coan A, Sampson JH, Gururangan S, Peters KB, McLendon RE, Norfleet JA, Lipp ES, Drappatz J, Wen PY, Friedman HS. Phase II study of Gleevec® plus hydroxyurea (HU) in adults with progressi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival at 6 Months	Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or death due to any cause.	From the date of study treatment initiation to the date of the first documented progression or death from any cause, whichever came first, assessed up to 69 months. For each participant, PFS was assessed at 6 months after treatment initiation.	No
Secondary	Median Progression-free Survival (PFS)	Time in months from the start of study treatment to the date of first progression according to Macdonald criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve.	From the date of study treatment initiation to the date of the first documented progression or death from any cause, whichever came first, assessed up to 69 months.	No
Secondary	Median Overall Survival (OS)	Time in months from the start of study treatment to date of death due to any cause. Patients alive at last follow-up are censored as of that follow-up date. Median OS was estimated using a Kaplan-Meier curve.	From the date of study treatment initiation to the date of death from any cause, assessed up to 69 months.	No
Secondary	Objective Response Rate	Percentage of participants with an objective response (complete response or partial response). Per modified Macdonald criteria and assessed by MRI, complete response (CR) was the disappearance of all target lesions and partial response (PR) was a =50% decrease in the sum of the longest diameter of target lesions. Objective response = CR+PR.	69 Months	No