Clinical trial NCT00124657: Erlotinib and Radiation Therapy in Treating Young Patients With Newly Diagnosed Glioma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: adult anaplastic astrocytoma
adult anaplastic oligodendroglioma
adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma
adult mixed glioma
childhood mixed glioma
untreated childhood cerebellar astrocytoma
childhood high-grade cerebral astrocytoma
childhood low-grade cerebral astrocytoma
childhood oligodendroglioma
childhood spinal cord neoplasm
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
Collaborators: name: Rady Children's Hospital, San Diego
name: Duke University
First posted: 2005-07-28
Enrollment: 62
Sex: ALL
Minimum age (years): 3
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Dose-limiting Toxicity (DLT)
timeFrame: During the first 8 weeks of therapy
measure: Maximum Tolerated Dose (MTD) of Erlotinib
timeFrame: During the first 8 weeks of therapy.
measure: Progression Free Survival (PFS)
timeFrame: 1 and 2 years after end of therapy
Secondary outcomes:
measure: Cmax of Erlotinib and Its Metabolite OSI-420
timeFrame: After first dose of therapy, and Day 8 of therapy
measure: Erlotinib Tmax
timeFrame: After first dose of therapy
measure: AUC Time 0-infinite (AUCinf) of Erlotinib and Its Metabolite OSI-420
timeFrame: After first dose of therapy, and Day 8 of therapy
measure: Number of Positive Mutations of EGFR and Downstream Pathways
timeFrame: Once at tumor resection and diagnosis
measure: Ability of Erlotinib to Inhibit EGFR Signaling
timeFrame: 5 Years
measure: Correlation Between Standard Magnetic Resonance Imaging and Investigational Radiologic Techniques in Assessing Tumor Response to This Treatment
timeFrame: at diagnosis and regular intervals during therapy (up to 2 years after start of therapy)
measure: 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
timeFrame: 5 Years
measure: Plasma and CSF Levels of VEGF, bFGF, and SDF1
timeFrame: at diagnosis and regular intervals during therapy (up to 2 years after start of therapy)
measure: Number of Participants Experiencing Grade 3 or 4 Toxicity Events
timeFrame: From start of therapy through 2 years.
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: Durham
country: United States
facility: Duke Children's Hospital and Health Center
state: North Carolina
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Alberto Broniscer, MD
role: PRINCIPAL_INVESTIGATOR
References: