Study Stopped
Poor accrual
Imatinib Mesylate With or Without Radiation Therapy in Treating Young Patients With Newly Diagnosed or Recurrent Glioma
A Phase I/II Trial Of STI571 In Children With Newly Diagnosed Poor Prognosis Brainstem Gliomas And Recurrent Intracranial Malignant Gliomas
4 other identifiers
interventional
85
1 country
10
Brief Summary
Phase I/II trial to estimate the maximum tolerated dose of imatinib mesylate in newly diagnosed brain stem gliomas and recurrent high grade gliomas and to assess the effectiveness of imatinib mesylate in treating young patients who have newly diagnosed intrinsic brain stem glioma. Imatinib mesylate may interfere with the growth of tumor cells by blocking the enzymes necessary for their growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining imatinib mesylate with radiation therapy may kill more tumor cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2001
Longer than P75 for phase_1
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2001
CompletedFirst Submitted
Initial submission to the registry
July 11, 2001
CompletedFirst Posted
Study publicly available on registry
January 27, 2003
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2008
CompletedResults Posted
Study results publicly available
April 9, 2010
CompletedJuly 31, 2014
February 1, 2013
7.3 years
July 11, 2001
February 9, 2010
July 25, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Number of Participants in Phase I Stratum I With Dose Limiting Toxicities (DLT) Observed During First 8 Weeks (Courses 1 and 2) of Imatinib Therapy
The dose limiting toxicity (DLT) analysis population consists of phase I stratum I participants who developed DLT during the maximum tolerated dose (MTD) estimation period (course 1 and 2) or who completed the MTD estimation period (courses 1 and 2) without DLTs. DLTs observed during courses 1 and 2 were used to estimate the MTD. The estimated MTD based on the 23 participants who either had a DLT during course 1 or 2 or completed courses 1 and 2 without DLT is 265 mg/m2/day.
Day 1 of Imatinib Mesylate Therapy to Week 8
Number of Participants in Phase I Stratum II With Dose Limiting Toxicities (DLT) Observed During First 8 Weeks (Courses 1 and 2) of Imatinib Therapy
The dose limiting toxicity (DLT) analysis population consisted of phase I stratum II participants who developed DLT during the maximum tolerated dose (MTD) estimation period (courses 1 and 2) or who completed the MTD estimation period (courses 1 and 2) without DLTs. DLTs observed during courses 1 and 2 were used to estimate the MTD. The estimated MTD based on the DLT analysis population of 20 in stratum IIA was 465 mg/m2/day. An MTD was not established in stratum IIB as no DLTs were observed at the higher dose levels of 620 and 800 mg/m2/day.
Day 1 of Imatinib Mesylate Therapy to Week 8
Median Progression-free Survival (PFS)
Progression-free survival is defined as the interval from initiation of treatment to the earliest of disease progression (tumor increase of 25% over baseline tumor measurement; appearance of new lesion(s); or progressive/worsening neurological status) or death for patients who failed, or to the last date of follow up for patients without failure.
Assessed pre-radiation, before the first dose of imatinib, and then every 8 weeks
Secondary Outcomes (7)
Change From Baseline in Volume FLAIR at Two Weeks After Completion of Radiation
Baseline and two weeks post completion of radiation
Peak Concentration (Cmax)
Day 1 of Course 1
Median Overall Survival
Assessed before radiation therapy, before the first dose of imatinib, then every 8 weeks.
Pre-treatment Basic Fibroblast Growth Factor Values From Urine
Pre-treatment
Pre-treatment Basic Fibroblast Growth Factor Values From Plasma
Pre-treatment
- +2 more secondary outcomes
Study Arms (1)
Imatinib mesylate
EXPERIMENTALInterventions
* Phase 1 Stratum I: Starting dose level of 350 mg/m2/day every 28 days X 13 courses (dose escalation) * Phase I Stratum IIA: Starting dose level of 465 mg/m2/day every 28 days X 13 courses (dose escalation) * Phase I Stratum IIB: Starting dose level of 465 mg/m2/day every 28 days X 13 courses (dose escalation) * Phase II: Phase I Stratum I determined dose (Maximum tolerated dose) every 28 days X 13 courses.
* Phase I Stratum I: Total dose of 5580 cGy using conventional or conformal volume-based delivery techniques once daily, 5 days/week for six weeks prior to receiving imatinib. * Phase II: Total dose of 5580 cGy using conventional or conformal volume-based delivery techniques once daily, 5 days/week for six weeks prior to receiving imatinib.
Eligibility Criteria
You may qualify if:
- Age 3 to 21
- Performance status of Karnofsky 50-100% OR Lansky 50-100%
- Absolute neutrophil count greater than 1,000/mm3
- Platelet count greater than 100,000/mm3 (transfusion independent)
- Hemoglobin greater than 8 g/dL (transfusion allowed)
- Bilirubin no greater than 1.5 times normal for age
- SGPT less than 3 times normal for age
- Albumin at least 2 g/dL
- Creatinine less than 1.5 times normal for age OR Glomerular filtration rate greater than 70 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception during and for 6 months after study participation
- Stratum I
- Newly diagnosed diffuse intrinsic brainstem malignant glioma
- No disseminated disease
- +14 more criteria
You may not qualify if:
- Receiving other anticancer or experimental drug therapy.
- Ongoing uncontrolled infection.
- Significant cardiac, hepatic, gastrointestinal, renal, pulmonary, or psychiatric disease.
- Deep venous or arterial thrombosis within 6 weeks of registration.
- Taking warfarin.
- Newly diagnosed diffuse intrinsic brainstem malignant glioma with disseminated disease (stratum I)
- Intratumoral hemorrhage
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (10)
UCSF Comprehensive Cancer Center
San Francisco, California, 94143, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010-2970, United States
Children's Memorial Hospital - Chicago
Chicago, Illinois, 60614, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, 02115, United States
Duke Comprehensive Cancer Center
Durham, North Carolina, 27710, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104-4318, United States
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15213, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105-2794, United States
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
Houston, Texas, 77030-2399, United States
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, 98105, United States
Related Publications (2)
Williams G, Fahey FH, Treves ST, Kocak M, Pollack IF, Boyett JM, Kun LE, Poussaint TY. Exploratory evaluation of two-dimensional and three-dimensional methods of FDG PET quantification in pediatric anaplastic astrocytoma: a report from the Pediatric Brain Tumor Consortium (PBTC). Eur J Nucl Med Mol Imaging. 2008 Sep;35(9):1651-8. doi: 10.1007/s00259-008-0780-7. Epub 2008 Apr 19.
PMID: 18425516RESULTPollack IF, Jakacki RI, Blaney SM, Hancock ML, Kieran MW, Phillips P, Kun LE, Friedman H, Packer R, Banerjee A, Geyer JR, Goldman S, Poussaint TY, Krasin MJ, Wang Y, Hayes M, Murgo A, Weiner S, Boyett JM. Phase I trial of imatinib in children with newly diagnosed brainstem and recurrent malignant gliomas: a Pediatric Brain Tumor Consortium report. Neuro Oncol. 2007 Apr;9(2):145-60. doi: 10.1215/15228517-2006-031. Epub 2007 Feb 9.
PMID: 17293590RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The phase II component of the trial was terminated because of poor accrual. Only one patient enrolled to the phase II component and did not receive the investigational drug.
Results Point of Contact
- Title
- Pediatric Brain Tumor Consortium (James M. Boyett, Ph.D)
- Organization
- Pediatric Brain Tumor Consortium
Study Officials
- STUDY CHAIR
Ian F. Pollack, MD
University of Pittsburgh
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 11, 2001
First Posted
January 27, 2003
Study Start
May 1, 2001
Primary Completion
August 1, 2008
Study Completion
August 1, 2008
Last Updated
July 31, 2014
Results First Posted
April 9, 2010
Record last verified: 2013-02