Clinical trial NCT00005951: Irinotecan Plus Temozolomide in Treating Patients With Recurrent Primary Malignant Glioma
Official title: Phase I Treatment of Adults With Primary Malignant Glioma With Irinotecan (CPT-11) (NSC- #6616348) Plus Temodar (NSC #362856)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Brain and Central Nervous System Tumors
Keywords: recurrent adult brain tumor
adult glioblastoma
adult anaplastic astrocytoma
adult anaplastic oligodendroglioma
adult mixed glioma
adult giant cell glioblastoma
adult gliosarcoma
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of irinotecan plus temozolomide in treating patients who have recurrent primary malignant glioma.

Detailed description: OBJECTIVES:

* Determine the maximum tolerated dose of irinotecan administered in combination with temozolomide in patients with recurrent primary malignant glioma.
* Determine the toxicity of this combination therapy in these patients.

OUTLINE: This is a dose escalation study of irinotecan. Patients are stratified according to concurrent anticonvulsants (Dilantin, Tegretol, or phenobarbital vs other anticonvulsants or none).

Patients receive irinotecan IV over 90 minutes on days 1, 8, 15, and 22 and oral temozolomide on days 1-5. Treatment continues every 43 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities.

PROJECTED ACCRUAL: Not specified

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed recurrent primary malignant glioma

  * Anaplastic astrocytoma
  * Glioblastoma multiforme
  * Anaplastic oligodendroglioma
  * Gliosarcoma
  * Anaplastic mixed oligoastrocytoma
* Measurable disease by MRI or CT
* No immediate radiotherapy required
* Neurologically stable for at least 2 weeks prior to study

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Karnofsky 60-100%

Life expectancy:

* Greater than 12 weeks

Hematopoietic:

* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3
* Hemoglobin at least 10 g/dL

Hepatic:

* Bilirubin less than 1.5 times upper limit of normal (ULN)
* SGOT and SGPT less than 2.5 times ULN
* Alkaline phosphatase less than 2 times ULN

Renal:

* Blood urea nitrogen and creatinine less than 1.5 times ULN

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* HIV negative
* No other nonmalignant systemic disease
* No acute infection treated with IV antibiotics
* No frequent vomiting or other condition that would preclude oral medication administration (e.g., partial bowel obstruction)
* No other prior malignancies except surgically cured carcinoma in situ of the cervix or basal or squamous cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No more than 1 prior biologic therapy regimen

Chemotherapy:

* No more than 1 prior chemotherapy regimen
* At least 6 weeks since prior chemotherapy, unless evidence of disease progression
* No prior failure of irinotecan or temozolomide

Endocrine therapy:

* Concurrent corticosteroids allowed

Radiotherapy:

* See Disease Characteristics
* At least 6 weeks since prior radiotherapy, unless evidence of disease progression

Surgery:

* At least 3 weeks since prior surgery, unless evidence of disease progression, and recovered

Other:

* No concurrent immunosuppressive agents

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: Duke Cancer Institute
name: Henry S. Friedman, MD
role: STUDY_CHAIR
References: