Phase II Imatinib + Hydroxyurea in Treatment of Patients With Recurrent/Progressive Grade II Low-Grade Glioma (LGG)

NCT00615927 | Completed Phase 2 Results DMC

• 1 other identifier: Pro00008799
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

Primary objective:

• To evaluate activity of imatinib mesylate and hydroxyurea among patients with progressive/recurrent grade II low-grade glioma (LGG) as measured by 12-month progression free survival Secondary objectives:
• To evaluate progression-free survival (PFS), overall survival and objective response rate among patients with progressive/recurrent grade II LGG treated with imatinib mesylate plus hydroxyurea
• To assess safety and tolerability of imatinib mesylate + hydroxyurea in this population

Conditions

Glioblastoma; Gliosarcoma

Keywords

Glioblastoma; Gliosarcoma; glioblastoma multiforme (GBM); GBM; Imatinib Mesylate; Gleevec; Hydroxyurea; Droxia; Hydrea; Hydroxycarbamide; Imatinib; Brain tumor; Malignant brain tumor; Recurrent glioblastoma multiforme; Progressive glioblastoma multiforme

Outcome Measures

Primary Outcomes (1)

• 12-month Progression Free Survival (PFS)

  Percentage of participants surviving twelve months from the start of cycle 1 without progression of disease. PFS was defined as the time from the cycle 1 start date to the date of the first documented progression according to modified Macdonald criteria, or to death due to any cause.

  12 months

Secondary Outcomes (4)

• Median Progression-free Survival

  Time in weeks from the start of cycle 1 to the date of first progression according to modified Macdonald criteria or to death due to any cause, assessed up to 156 weeks

• Median Overall Survival (OS)

  Time in weeks from the start of cycle 1 to date of death due to any cause, assessed up to 156 weeks

• Objective Response Rate

  156 weeks

• Safety and Tolerability of Gleevec + Hydroxyurea in Patients With Low-grade Gliomas

  156 weeks

Study Arms (2)

Astrocytoma

EXPERIMENTAL

Grade II Astrocytoma

Drug: Imatinib Mesylate & Hydroxyurea

Oligodendroglioma

EXPERIMENTAL

Grade II Oligodendroglioma or oligoastrocytomas

Drug: Imatinib Mesylate & Hydroxyurea

Interventions

Imatinib Mesylate & Hydroxyurea DRUG

Imatinib administered orally on daily. Imatinib is local irritant \& must be taken in sitting position; mini of 2hrs should be allowed between last drug intake \& going to bed. Imatinib doses 400mg/600mg administered once daily, whereas daily doses of 800mg/\> administered as equally divided dose taken twice day. Dose for imatinib: Pts not receiving p450-inducing antiepileptic drugs: 400 mg/day. Pts receiving p450-inducing antiepileptic drugs: 500 mg twice day. It is recommended that pts take their prescribed imatinib mesylate at same time that they take their prescribed hydroxyurea, however, 30-60min interval between agents is acceptable if required for practical/other compliance issues. Hydroxyurea administered orally twice day. Dosing will begin on day 1 of cycle 1 \& continue daily. Drug is approximately 80 percent bioavailable. Dose will be 500mg twice day for all pts.

Also known as: Imatinib Mesylate-Gleevec, Hydroxyurea-Droxia-Hydrea-Hydroxycarbamide

Astrocytoma; Oligodendroglioma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with grade II LGG that is recurrent/progressive following prior surgical resection while on non-decreasing dose of corticosteroids
• \> 25percent enlargement of bidimensional measure/new lesions on sequential imaging new \&/or worsening neurologic deficits
• Patients with progressive/recurrent optic pathway tumors
• Patients have measurable disease on MRI/CT
• Interval of \> 4 wks between prior external beam radiation therapy (XRT)/chemo,\& enrollment on protocol unless there is unequivocal evidence of tumor progression \& patient has recovered from all expected toxicities associated with prior therapy. Patients treated w chemo agents such as VP-16 who would normally be retreated after shorter intervals may be treated at usual starting time even if \< 4 wks from last prior dose of chemo
• Patients not have had tumor biopsy \< 1 wk/surgical resection \< 2 wks prior to starting study drug
• Patients enrolling on arm B must be on \> 1 enzyme inducing anticonvulsants for \>2 wks prior to starting study drug
• Patients should be on non-increasing dose of steroids for \> 7 days prior to obtaining baseline Gd-MRI of brain
• Patients should be on non-increasing dose of steroids for \> 7 days prior to starting study drug
• Multifocal disease is eligible
• Age \> 18 yrs old
• Karnofsky Performance Status (KPS) of \> 60
• absolute neutrophil count (ANC) \> 1.5 x 10 9/L
• Hgb \> 9 g/dL
• Platelets \> 100 x 10 9/L

You may not qualify if:

• Prior progressive disease/toxicity grade ≥ 3 with prior hydroxyurea therapy
• Prior treatment with imatinib/other platelet derived growth factor (PDGF)-directed therapy
• Excessive risk of bleeding as defined by stroke \< 6 months, history of central nervous system (CNS)/intraocular bleed, or septic endocarditis
• Evidence of intratumor hemorrhage on pretreatment diagnostic imaging, except for stable post-operative gr1 hemorrhage
• Pregnant/breast feeding, /adults of reproductive potential not employing effective method of birth control
• Concurrent severe and/or uncontrolled medical disease that could compromise participation in study
• Acute/chronic liver disease
• Confirmed diagnosis of HIV infection
• Impairment of GI function/GI disease that may significantly alter absorption of imatinib
• Patients taking Coumadin
• Patients have received investigational drugs \< 2wks prior to entry on study/have not recovered from toxic effects of such therapy
• Patients have received biologic, immunotherapeutic/cytostatic agents \< 1 wk prior to entry on study/have not recovered from toxic effects of such therapy
• Patient \> 5 yrs free of another primary malignancy except: if other primary malignancy is not currently clinically significant/requiring active intervention, or if other primary malignancy is basal cell skin cancer/ cervical carcinoma in situ. Existence of any other malignant disease is not allowed
• Patients have had any surgery other than resection of brain tumor \< 2 wks prior to entry on study/have not recovered from side effects of such therapy
• Patients unwilling to/unable to comply with protocol

Sponsors & Collaborators

• Duke University: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Related Links

• The Preston Robert Tisch Brain Tumor Center at DUKE

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Brain Neoplasms

Interventions

Imatinib Mesylate; Hydroxyurea

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Urea

Results Point of Contact

• Title: Annick Desjardins, MD, FRCPC
• Organization: Duke University Medical Center

annick.desjardins@dm.duke.edu

919-668-

Study Officials

• Annick Desjardins, MD, FRCPC

  Duke Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2008
• First Posted: February 14, 2008
• Study Start: February 1, 2006
• Primary Completion: April 1, 2009
• Study Completion: June 1, 2012
• Last Updated: March 15, 2013
• Results First Posted: March 15, 2013

Record last verified: 2012-12

Locations

US (1)