Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

Erlotinib and Radiation Therapy in Treating Young Patients With Newly Diagnosed Glioma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00124657
Recruitment Status : Completed
First Posted : July 28, 2005
Results First Posted : April 29, 2014
Last Update Posted : December 4, 2015
Sponsor:
Collaborators:
Rady Children's Hospital, San Diego
Duke University
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Tracking Information
First Submitted Date  ICMJE July 26, 2005
First Posted Date  ICMJE July 28, 2005
Results First Submitted Date  ICMJE September 10, 2013
Results First Posted Date  ICMJE April 29, 2014
Last Update Posted Date December 4, 2015
Study Start Date  ICMJE March 2005
Actual Primary Completion Date July 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 27, 2014)
  • Number of Participants With Dose-limiting Toxicity (DLT) [ Time Frame: During the first 8 weeks of therapy ]
    DLT was defined as any of the following toxicities attributable to erlotinib therapy: thrombocytopenia grade 3 and 4; neutropenia grade 4; or any grade 3 and 4 non-hematologic toxicity except for grade 3 diarrhea and grade 3 nausea and vomiting lasting ≤48 hours in participants not receiving optimal supportive therapy, grade 3 skin rash, which did not affect normal daily activities, grade 3 fever or nonneutropenic infection, grade 3 seizures, grade 3 weight gain or loss, and grade 3 transaminase elevation that returned to grade 1 or baseline within 7 days. After enrollment of the first 4 participants, grade 3 and 4 electrolyte abnormalities that resolved to ≤grade 2 within 7 days were excluded as DLT. Toxicities were graded according to the Common Terminology Criteria for Adverse Events version 3.0.
  • Maximum Tolerated Dose (MTD) of Erlotinib [ Time Frame: During the first 8 weeks of therapy. ]
    MTD was defined as the highest dosage level in which no more than one of six assessable participants experienced dose-limiting toxicities (DLT). The dosage of erlotinib was increased by approximately 30% in each dosage level starting at 80% of the MTD in adults with solid tumors. A traditional 3+3 dose escalation scheme was used to estimate the MTD.
  • Progression Free Survival (PFS) [ Time Frame: 1 and 2 years after end of therapy ]
    Progression-free survival (PFS) distributions for the Phase II participants with anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM) were calculated using Kaplan-Meier estimates (n=41). PFS was defined as the interval between treatment start and initial failure, including clinical or radiologic progression or death from any cause. PFS was not calculated for the other disease types.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00124657 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 29, 2015)
  • Cmax of Erlotinib and Its Metabolite OSI-420 [ Time Frame: After first dose of therapy, and Day 8 of therapy ]
    Although the calculated dose of erlotinib was rounded to the nearest 25 mg, the actual dosage administered to patients was within 12% of the prescribed dosage in all but 1 patient. The latter patient received erlotinib at the lowest dosage level and the actual dosage was 19% higher than the calculated dose.
  • Erlotinib Tmax [ Time Frame: After first dose of therapy ]
    Although the calculated dose of erlotinib was rounded to the nearest 25 mg, the actual dosage administered to patients was within 12% of the prescribed dosage in all but 1 patient. The latter patient received erlotinib at the lowest dosage level and the actual dosage was 19% higher than the calculated dose.
  • AUC Time 0-infinite (AUCinf) of Erlotinib and Its Metabolite OSI-420 [ Time Frame: After first dose of therapy, and Day 8 of therapy ]
    Although the calculated dose of erlotinib was rounded to the nearest 25 mg, the actual dosage administered to patients was within 12% of the prescribed dosage in all but 1 patient. The latter patient received erlotinib at the lowest dosage level and the actual dosage was 19% higher than the calculated dose.
  • Number of Positive Mutations of EGFR and Downstream Pathways [ Time Frame: Once at tumor resection and diagnosis ]
    Statistical analyses of genomic changes, expression profiles and validation studies should be considered in an exploratory and hypothesis-generating context. Fresh frozen tumor tissue was obtained at the time of tumor resection and diagnosis. DNA was extracted from formalin-fixed, paraffin-embedded tissue. The entire PTEN coding sequence (exons 1-9), exons 1, 9 and 20 of PIK3CA, and exons 17-24 of EGFR were evaluated using exon-specific PCR amplification, and immunohistochemistry was done. Tumor lesions were considered positive if >25% cells were immunoreactive.
  • Ability of Erlotinib to Inhibit EGFR Signaling [ Time Frame: 5 Years ]
    The objective was to test the ability of erlotinib to inhibit the EGFR signaling in patients with high-grade glioma who required a second surgery. This outcome was not assessed due to insufficient availability of tumor and control samples for analysis.
  • Correlation Between Standard Magnetic Resonance Imaging and Investigational Radiologic Techniques in Assessing Tumor Response to This Treatment [ Time Frame: at diagnosis and regular intervals during therapy (up to 2 years after start of therapy) ]
    This objective was to prospectively investigate the correlation between standard magnetic resonance imaging (MRI) and investigational radiologic techniques (MR spectroscopy, perfusion/diffusion, PET scan, DEMRI/BLAST) in assessing tumor response to this treatment.
  • To Prospectively Investigate the Technical Factors Involved in Planning and Administering Conformal Fractionated RT as Outlined in This Study, and to Correlate RT Dosimetry With Patterns of Failure, Standard and Investigational Imaging and Toxicity [ Time Frame: 5 Years ]
  • Plasma and CSF Levels of VEGF, bFGF, and SDF1 [ Time Frame: at diagnosis and regular intervals during therapy (up to 2 years after start of therapy) ]
    This objective was to determine the plasma and CSF levels of the VEGF, bFGF, and SDF1 at diagnosis, and the plasma levels of these factors at regular intervals during therapy, and to analyze the association of these results with tumor response.
  • Number of Participants Experiencing Grade 3 or 4 Toxicity Events [ Time Frame: From start of therapy through 2 years. ]
    Adverse events were collected systematically for each of the 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Erlotinib and Radiation Therapy in Treating Young Patients With Newly Diagnosed Glioma
Official Title  ICMJE A Phase I/II Trial of a New Tyrosine Kinase Inhibitor (Tarceva; Erlotinib Hydrochloride; OSI-774) During and After Radiotherapy in the Treatment of Patients With Newly Diagnosed High Grade Glioma and Unfavorable Low-Grade Glioma
Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It may also make tumor cells more sensitive to radiation therapy. Giving radiation therapy together with erlotinib may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of erlotinib when given together with radiation therapy and to see how well they work in treating young patients with newly diagnosed glioma.

Detailed Description

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose and dose-limiting toxicity of erlotinib when administered during and after radiotherapy in young patients with newly diagnosed high-grade glioma and unfavorable low-grade glioma.
  • Determine the 1- and 2-year progression-free survival of patients treated with this regimen.

Secondary

  • Determine the toxic effects of this regimen in these patients.
  • Correlate genetic abnormalities in epidermal growth factor receptor (EGFR) and components of downstream pathways with treatment response in patients treated with this regimen.
  • Determine the ability of erlotinib to inhibit EGFR signaling in patients with high-grade glioma who require second surgery.
  • Determine the pharmacokinetics of erlotinib and its metabolites in these patients.
  • Correlate plasma and cerebrospinal fluid levels of vascular endothelial growth factor and basic fibroblast growth factor with tumor response in patients treated with this regimen.
  • Correlate irradiation dosimetry with patterns of failure, standard and investigational imaging, and toxicity in patients treated with this regimen.

OUTLINE: This is a phase I dose-escalation study of erlotinib followed by a phase II study.

  • Phase I: Patients undergo radiotherapy once daily, 5 days week, for approximately 6½ weeks. Beginning on the first day of radiotherapy, patients receive oral erlotinib once daily for up to 2 years.

Cohorts of patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined.

  • Phase II: Patients will receive erlotinib as in phase I at the MTD and undergo radiotherapy as in phase I.

PROJECTED ACCRUAL: A total of 75-80 patients (15-20 for the phase I portion and 60 for the phase II portion) will be accrued for this study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Brain and Central Nervous System Tumors
Intervention  ICMJE Drug: Erlotinib hydrochloride
This study has 2 components: a Phase I component which estimated the MTD and DLT(s) of erlotinib given once a day during and after conventionally fractionated RT for a period of 8 weeks (DLT-evaluation period), followed by continuous administration of this medication for up to 3 years; and a Phase II component where erlotinib will be given at the MTD during and after RT for 2 years. The recommended dose of erlotinib for the Phase II component of the current study is 120mg/m2 per day (maximum dose of 200mg per day).
Other Names:
  • Tarceva
  • OSI-774
  • NSC#718781
Study Arms  ICMJE Experimental: Patients with High-Grade/Low-Grade Glioma
Patients with newly diagnosed high-grade glioma (excluding those originating in the brain stem) and unfavorable low-grade glioma who are ≥ 3 years and <26 years of age. Patients receiving enzyme-inducing anticonvulsants (EIACs) are not eligible for this study. Patients with spinal cord tumors will be eligible for the Phase I and Phase II component of this study, but they will not be taken into consideration to estimate PFS in the Phase II component of this trial because of their notoriously worse prognosis. Patients receive erlotinib hydrochloride.
Intervention: Drug: Erlotinib hydrochloride
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 27, 2014)
62
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE September 2014
Actual Primary Completion Date July 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Diagnosis of high-grade glioma of 1 of the following types:

    • Unfavorable low-grade glioma

      • Gliomatosis cerebri or bithalamic involvement
    • Histologically confirmed high-grade glioma (WHO grade III or IV) of 1 of the following subtypes:

      • Anaplastic astrocytoma
      • Anaplastic oligodendroglioma
      • Anaplastic oligoastrocytoma
      • Anaplastic ganglioglioma
      • Pleomorphic xanthoastrocytoma with anaplastic features
      • Malignant glioneuronal tumor
      • Glioblastoma multiforme
      • Gliosarcoma
  • Newly diagnosed disease
  • Intracranial or spinal cord tumors allowed

PATIENT CHARACTERISTICS:

Age

  • 3 to 21

Performance status

  • Karnofsky 40-100% (age 17 to 21 years) OR
  • Lansky 40-100% (age 3 to 16 years)

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3 (transfusion independent)
  • Hemoglobin ≥ 8 g/dL (transfusion allowed)

Hepatic

  • Bilirubin < 1.5 times upper limit of normal (ULN)
  • SGPT < 5 times ULN
  • Albumin ≥ 2 g/dL

Renal

  • Creatinine < 2 times normal OR
  • Glomerular filtration rate > 70 mL/min

Cardiovascular

  • No significant cardiovascular problem

Pulmonary

  • No significant pulmonary problem

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No uncontrolled infection
  • No significant medical illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior or concurrent biologic agents

Chemotherapy

  • No prior or concurrent chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior radiotherapy

Surgery

  • No more than 42 days since prior surgery

Other

  • No other prior or concurrent anticancer or experimental treatment
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00124657
Other Study ID Numbers  ICMJE SJHG04
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party St. Jude Children's Research Hospital
Study Sponsor  ICMJE St. Jude Children's Research Hospital
Collaborators  ICMJE
  • Rady Children's Hospital, San Diego
  • Duke University
Investigators  ICMJE
Principal Investigator: Alberto Broniscer, MD St. Jude Children's Research Hospital
PRS Account St. Jude Children's Research Hospital
Verification Date October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP