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A Phase I/II Study of an Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI), ZD 1839 (Iressa), [NSC #715055] With Radiation Therapy in Glioblastoma Multiforme

Phase 1/Phase 2
Not Enrolling
Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma

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Trial Information

A Phase I/II Study of an Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI), ZD 1839 (Iressa), [NSC #715055] With Radiation Therapy in Glioblastoma Multiforme


I. To identify the maximum tolerated dose of ZD 1839 (gefitinib) when given concurrently
with cranial radiotherapy.

II. To determine if ZD 1839, given orally on a daily basis starting at the time of
conventional radiation therapy (RT), may improve the overall survival of adults with
newly-diagnosed supratentorial glioblastoma multiforme, compared with historical controls,
stratifying by epidermal growth factor receptor (EGFR) status.

III. To determine, in a multi-institutional setting, the feasibility and toxicity of
prescribing ZD 1839.


I. Whether ZD 1839 also improves progression-free survival in these patients.

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

Patients receive gefitinib orally (PO) once daily (QD) for 7 weeks. Beginning 1 week after
initiation of gefitinib, patients undergo radiation therapy QD 5 days a week for 6 weeks.
Treatment with gefitinib continues for up to 18 months in the absence of disease progression
or unacceptable toxicity.

After completion of study treatment, patients are followed up every 4 months for 1 year,
every 6 months for 2 years, and annually thereafter.

Inclusion Criteria:

- Histopathologically confirmed glioblastoma multiforme (with areas of necrosis)

- Diagnosis must be made by surgical biopsy or excision

- The tumor must be supratentorial in location

- The patient must have recovered from the effects of surgery, post-operative
infection, or other complications before study entry

- Radiotherapy must begin =< five weeks after surgery, and Iressa (gefitinib) must
begin one week prior to radiotherapy

- Patients must have an estimated survival of at least 8 weeks

- Zubrod performance status of 0-1

- A diagnostic contrast-enhanced magnetic resonance imaging (MRI) or computed
tomography (CT) scan must be performed preoperatively and postoperatively prior to
the initiation of radiotherapy; preoperative and postoperative scans must be the same

- Patients diagnosed only by stereotactic biopsy do not require the postoperative scan

- Patients unable to undergo magnetic resonance (MR) imaging because of non-compatible
devices can be enrolled, provided pre and postoperative CT scans are obtained and are
of sufficient quality

- Hemoglobin >= 10 grams

- Absolute neutrophil count >= 1500 (ANC) per mm^3

- Platelets >= 100,000 per mm^3

- Blood urea nitrogen (BUN) =< 25 mg

- Creatinine =< 1.5 mg

- Bilirubin =< 2.0 mg

- Serum glutamate pyruvate transaminase (SGPT) or serum glutamic oxaloacetic
transaminase (SGOT) =< 2 x normal range

- Patients must consent to submission of their tissue/serum

- The patient must sign a study-specific informed consent prior to study entry; if the
patient's mental status precludes his/her giving informed consent, written informed
consent may be given by the responsible family member

Exclusion Criteria:

- Recurrent or multifocal malignant gliomas

- Metastases detected below the tentorium or beyond the cranial vault

- Major medical illnesses or psychiatric impairments which, in the investigator's
opinion, will prevent administration or completion of protocol therapy

- Previous radiotherapy to the head or neck (except for T1 glottic cancer), resulting
in overlap of radiation fields

- Active connective tissue disorders, such as lupus or scleroderma which, in the
opinion of the treating physician, may put the patient at high risk for radiation

- Previous malignancies, except for non-melanomatous skin cancers and carcinoma in situ
of the uterine cervix or bladder, unless disease-free for >= 3 years

- Prior chemotherapy or radiosensitizers for cancers of the head and neck region

- Patients with known acquired immune deficiency (AIDS); patients with AIDS require
complex therapeutic regimens; the pharmacokinetic interactions of these regimens with
ZD 1839 are unknown and therefore, pose a safety risk related to excess toxicity or
interference with anti-viral effectiveness

- Patients with known multiple sclerosis, as these patients may have decreased
tolerance for radiation therapy to the brain

- Pregnant or lactating women, due to possible adverse effects on the developing fetus
or infant due to study drug

- Patients treated on any other clinical protocols within 30 days prior to study entry
or during participation in the study

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of gefitinib defined as the dose at which no patients develop acute grade 5 toxicity and less than 30% of patients developed acute dose limiting toxicity graded by the National Cancer Institute Common Toxicity Criteria v2.0

Outcome Time Frame:

Within 90 days from the start of radiotherapy treatment

Safety Issue:


Principal Investigator

Arnab Chakravarti

Investigator Role:

Principal Investigator

Investigator Affiliation:

Radiation Therapy Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

March 2002

Completion Date:

Related Keywords:

  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Glioblastoma
  • Gliosarcoma



Radiation Therapy Oncology Group Philadelphia, Pennsylvania  19107