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

NCT00124657 | Completed Phase 1 Results DMC

• 1 other identifier: SJHG04
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 3

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.

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

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Dose-limiting Toxicity (DLT)

  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.

  During the first 8 weeks of therapy

• Maximum Tolerated Dose (MTD) of Erlotinib

  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.

  During the first 8 weeks of therapy.

• Progression Free Survival (PFS)

  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.

  1 and 2 years after end of therapy

Secondary Outcomes (9)

• Cmax of Erlotinib and Its Metabolite OSI-420

  After first dose of therapy, and Day 8 of therapy

• Erlotinib Tmax

  After first dose of therapy

• AUC Time 0-infinite (AUCinf) of Erlotinib and Its Metabolite OSI-420

  After first dose of therapy, and Day 8 of therapy

• Number of Positive Mutations of EGFR and Downstream Pathways

  Once at tumor resection and diagnosis

• Ability of Erlotinib to Inhibit EGFR Signaling

  5 Years

Study Arms (1)

Patients with High-Grade/Low-Grade Glioma

EXPERIMENTAL

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.

Drug: Erlotinib hydrochloride

Interventions

Erlotinib hydrochloride DRUG

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).

Also known as: Tarceva, OSI-774, NSC#718781

Patients with High-Grade/Low-Grade Glioma

Eligibility Criteria

• Age: 3 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• Rady Children's Hospital, San Diego: collaborator
• Duke University: collaborator

Study Sites (3)

University of California San Diego

San Diego, California, 92123-4282, United States

Location

Duke Children's Hospital and Health Center

Durham, North Carolina, 27710, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Central Nervous System Neoplasms; Astrocytoma; Oligodendroglioma; Glioblastoma; Gliosarcoma; Glioma; Spinal Cord Neoplasms

Interventions

Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Alberto Broniscer, MD
• Organization: St. Jude Children's Research Hospital

info@stjude.org

866-966-5934

Study Officials

• Alberto Broniscer, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2005
• First Posted: July 28, 2005
• Study Start: March 1, 2005
• Primary Completion: July 1, 2012
• Study Completion: September 1, 2014
• Last Updated: December 4, 2015
• Results First Posted: April 29, 2014

Record last verified: 2015-10

Locations

US (3)