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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
N/A
N/A
Not Enrolling
Both
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


PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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
type

- 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
toxicity

- 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:

Interventional

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:

Yes

Principal Investigator

Arnab Chakravarti

Investigator Role:

Principal Investigator

Investigator Affiliation:

Radiation Therapy Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2013-00849

NCT ID:

NCT00052208

Start Date:

March 2002

Completion Date:

Related Keywords:

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

Name

Location

Radiation Therapy Oncology GroupPhiladelphia, Pennsylvania  19107