Gefitinib and Radiation Therapy in Treating Children With Newly Diagnosed Gliomas

NCT00042991 | Completed Phase 1 Results

• 3 other identifiers: NCI-2012-03022PBTC-007U01CA081457
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

Biological therapies such as gefitinib may interfere with the growth of the tumor cells and may make the tumor cells more sensitive to radiation therapy. This phase I/II trial is studying how well giving gefitinib together with radiation therapy works in treating children with newly diagnosed glioma.

Conditions

Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Anaplastic Oligodendroglioma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliomatosis Cerebri; Untreated Childhood Gliosarcoma; Untreated Childhood Oligodendroglioma

Outcome Measures

Primary Outcomes (3)

• Number of Participants in Phase I Stratum 1A With Dose-limiting Toxicities (DLT) Observed During the First 8 Weeks of Gefitinib Therapy

  The dose limiting toxicity (DLT) analysis population consists of stratum 1A phase I participants who developed DLT during the maximum tolerated dose (MTD) estimation period (course 1 and 2) or who completed the MTD estimation period without DLTs. DLTs observed during courses 1 and 2 were used to estimate the MTD based on the tradional 3+3 design, where a dose is considered a safe dose only when 0 out of 3, or at most 1 out of 6 patients has DLTs. When two or more patients in a group of 2 to 6 patients had DLTs, then that dose level was considered to be too toxic.

  Day 1 of gefitinib therapy to end of week 8

• Median Progression-free Survival in Newly Diagnosed Brain Stem Gliomas

  Progression-free survival is defined as the interval from intiation of treatment to the earliest of disease progression (tumor increase of 25% over baseline tumor measurement; appearance of new lesion(s); or progressive/worsening neurlogical status) or death for patients who failed or to the last date of follow-up for patients without failure

  Assessed pre-radiation, every 8 weeks for 13 courses of therapy, and then every 12 weeks

• Median Survival in Newly Diagnosed Brain Stem Gliomas

  Overall survival is defined as the interval from initiation of treatment to death or date of last contact for surviving patients

  Assessed from the start of therapy until three years after initiation of gefitinib therapy

Secondary Outcomes (12)

• Change in Tumor Volume Measured on Fluid Attenuated Inversion Recovery (FLAIR) Imaging at Before the Protocol Therapy Started and at Two Weeks After Completion of Radiation

  Baseline and two weeks post completion of radiation

• Change From Baseline in Volume Enhancing at Two Weeks After Completion of Radiation

  Baseline and two weeks post completion of radiation

• Change From Baseline in Diffusion Ratio at Two Weeks After Completion of Radiation

  Baseline and two weeks post completion of radiation

• Change From Baseline in Perfusion Ratio at Two Weeks After Completion of Radiation

  Baseline and two weeks post completion of radiation

• Mean Tumor to Gray Matter Ratio Measured at Baseline

  Baseline

Study Arms (1)

Treatment (gefitinib and radiation therapy)

EXPERIMENTAL

Phase I portion: Patients receive oral gefitinib once daily. Treatment repeats every 4 weeks for 13 courses (1 year). Patients also receive standard brain irradiation once daily, 5 days a week, for 6 weeks beginning concurrently with initiation of the first course of gefitinib. Treatment continues in the absence of disease progression or unacceptable toxicity. Phase II portion: Once the MTD or the recommended Phase-II dose is determined, additional patients who have newly diagnosed BSG are treated at the MTD or the recommended Phase-II dose.

Drug: gefitinib; Radiation: radiation therapy; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

gefitinib DRUG

Given orally

Also known as: Iressa

Treatment (gefitinib and radiation therapy)

radiation therapy RADIATION

Undergo standard brain irradiation

Also known as: irradiation, radiotherapy, therapy, radiation

Treatment (gefitinib and radiation therapy)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (gefitinib and radiation therapy)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (gefitinib and radiation therapy)

Eligibility Criteria

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

You may qualify if:

• Tumor:
• Phase I: newly diagnosed non-disseminated diffuse intrinsic brainstem tumor or newly diagnosed (diagnostic scan must be within 4 weeks prior to treatment initiation), incompletely resected supratentorial malignant glioma (anaplastic astrocytoma, glioblastoma multiforme or other high-grade glioma) (STMG); the STMG group must have residual tumor evident on postoperative MRI or CT
• Phase II: only newly diagnosed non-disseminated diffuse intrinsic brain stem glioma patients are eligible
• Performance status: Karnofsky or Lansky \>= 50% assessed within two weeks prior to registration
• Prior/concurrent therapy:
• Chemotherapy: no prior therapy allowed, including prior gefitinib treatment
• Radiation therapy (XRT): no prior therapy allowed
• Bone marrow transplant: none prior
• Anti-convulsants: patients with brain stem glioma (BSG) receiving EIACD will not be eligible; patients with STMG will be eligible for this study even if they are receiving enzyme inducting anti-convulsant drugs (EIACD) and will be stratified by use of EIACDs
• Growth factors: off all colony forming growth factor(s) \> 2 weeks prior to registration (G-CSF, GM-CSF, erythropoietin)
• ANC \> 1,000/ul
• Platelets \> 100,000/ul (transfusion independent)
• Hemoglobin \> 8g/dl (may be transfused)
• Patients may have bone marrow involvement by disease
• Creatinine \< 2 x normal for age or GFR \> 70 ml/min/1.73m\^2

You may not qualify if:

• Patients with evidence of intramural hemorrhage on a scan obtained prior to enrollment or after enrollment, before treatment
• Patients with BSG must not be taking enzyme-inducing anticonvulsant drugs
• Patient must not be receiving any other anticancer or experimental drug therapy
• Patient must have no uncontrolled infection
• Patients with significant cardiac, hepatic, gastrointestinal, renal, pulmonary, or psychiatric disease are ineligible; patients with deep venous or arterial thrombosis within 6 weeks of study entry are ineligible
• Patients with disseminated disease are not permitted
• Patients with spinal disease requiring craniospinal radiation are not eligible
• Patients with completely resected supratentorial malignant gliomas patients are ineligible

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Pediatric Brain Tumor Consortium

Memphis, Tennessee, 38105, United States

Location

MeSH Terms

Interventions

Gefitinib; Radiotherapy; Radiation

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Therapeutics; Physical Phenomena

Results Point of Contact

• Title: Mehmet Kocak
• Organization: Operations and Biostatistics Center for Pediatric Brain Tumor Consortium (PBTC)

mehmet.kocak@stjude.org

9015952947

Study Officials

• Jeffrey Geyer

  Pediatric Brain Tumor Consortium

  PRINCIPAL INVESTIGATOR

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: August 5, 2002
• First Posted: January 27, 2003
• Study Start: July 1, 2002
• Primary Completion: February 1, 2010
• Study Completion: March 1, 2010
• Last Updated: May 28, 2014
• Results First Posted: July 11, 2011

Record last verified: 2012-12

Locations

US (1)