Phase II Study of Irinotecan HCI for Recurrent Anaplastic Astrocytomas, Mixed Malignant Gliomas, and Oligodendrogliomas

Condition(s) targeted: Recurrent Anaplastic Astrocytoma; Mixed Malignant Glioma; Oligodendroglioma

Intervention: Irinotecan HCL (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: H. Lee Moffitt Cancer Center and Research Institute

Official(s) and/or principal investigator(s):
Marc C Chamberlain, MD, Principal Investigator, Affiliation: H. Lee Moffitt Cancer Center and Research Institute

Phase 2 trial to explore the efficacy and safety of irinotecan (CPT-11) (also administered at each cycle is zofran/Kytril/Anzemet, decadron, and IV atropine). A treatment cycle is 21 days. Patients will be treated for a minimum of 3 cycles (doses) of CPT-11 or until their disease progresses. For patients responding to treatment, therapy may be continued beyond 18 cycles.

At each cycle, patient exams and interviews as well as lab results will help the research team to determine the symptomatic side effects of the treatment. Recorded past toxicities will be compared with current side effects.

Official title: A Phase II Study of Irinotecan HCI in Patients With Recurrent Anaplastic Astrocytomas, Mixed Malignant Gliomas, and Oligodendrogliomas

Study design: Diagnostic, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Primary outcome: Objective response rate after 3 cycles

Secondary outcome:

Overall survival and at 6 & 12 months

Progression free survival

frequency and severity of Toxicity

Detailed description: Phase 2 trial to explore the efficacy and safety of irinotecan (CPT-11) in patients with recurrent anaplastic astrocytomas (AA), mixed malignant glioma, and oligodendrogliomas (OA). Patients will be stratified by tumor histology and treated with CPT-11 every 21 days (treatment cycle).

Baseline data (collected <14 days) will consist of a neurological/oncological history, neurological examination, height, weight, performance status, Quality Of Life FACT-L questionnaire, laboratory studies to include CBC, differential, platelets, PT, CMP, LDH, and a pregnancy test, as well as a cranial CT/MRI with and without contrast (to measure or evaluate the size and location of the tumor before treatment).

Administered every 21 days is a dose of irinotecan (CPT-11), zofran/Kytril/Anzemet, decadron, and (IV) atropine. At each cycle, patient exams and interviews as well as lab results will help the research team to determine the symptomatic side effects of the treatment. Recorded past toxicities will be compared with current side effects.

Between days 15-21 (within 7 days of next scheduled CPT-11 treatment) the following tests

will be repeated - a neurological/oncological history and neurological examination, weight,

blood drawn (CMP, LDH), performance status, and Quality Of Life FACT-L questionnaire. Also, a MRI (Cranial CT/MRI with and without contrast) will be performed for tumor assessments at week 9, 18, 27, 36, and after every nine weeks thereafter until progression. Response is measured by a reduction in tumor size.

These supportive therapies will be provided as necessary:

- Antiemetic Therapy

- Anticholinergics

- Loperamide (Imodium®)

- Growth Factors

- Other Concomitant Medications

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients must have histological or neuroradiographic documented recurrent glioma

defined as an anaplastic astrocytoma, mixed malignant glioma or oligodendroglioma. All patients must have had prior pathologic confirmation of primary tumor histology.

- Patients must be > than or equal to 18 years old.

- Patients must have a KPS of > or equal to 50

- Measurable disease per MacDonald criteria is required

- Patients must have a predicted life expectancy of at least 12 weeks

- Required initial laboratory data:

1. ANC > 1,500

2. Platelets > 100,000

3. Serum Creatinine < 2. 0

4. Serum Bilirubin < 2. 0

5. AST/ALT < 3x normal

6. Pregnancy test for females with child-bearing potential negative

- Patients must sign and date an IRB approved informed consent form stating he or she is

aware of the neoplastic nature of the disease. Patient must willingly provide written consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts. (Human protection committee approval of this protocol and consent form is required).

- Patients must be willing and able to comply with scheduled visits, treatment plan, and

laboratory tests and accessible for follow-up.

- Patients must have been previously treated with both surgery and radiotherapy.

- Prior adjuvant and one salvage chemotherapy regimen is permitted. 11. Prior

stereotactic radiotherapy is permitted.

Exclusion Criteria:

- Patients have evidence of leptomeningeal spread of disease.

- Patients having been treated with 2 or more salvage regimens.

- Pregnant or breast-feeding women. With the exception of post-menopausal or infertile

women, a negative blood test for pregnancy is mandatory before entry on study. Fertile persons refusing to use adequate contraceptives may not participate.

- Patients with a history of irritable bowel disease, irritable bowel syndrome, chronic

diarrhea or presence of a bowel obstruction.

- Patients with a second active malignancy or diagnosis of other cancer within 3 years

of enrollment, except for surgically cured basal cell carcinoma, or in situ carcinoma of the cervix.

- Mentally incapacitated patients or psychiatric illness that would prevent the patient

from giving informed consent.

- Patients with poorly controlled diabetes, hepatitis infection, uncontrolled high blood

pressure, unstable angina, symptomatic congestive heart failure, and myocardial infarction within the previous six months, or serious uncontrolled cardiac arrhythmia.

- Known to be HIV positive or to have an AIDS-related illness.

- Patients with an active infection that is not adequately controlled with antibiotics.

- Patients with other severe concurrent disease, which, in the judgment of the

investigator, would make the patient inappropriate for entry into this study.

- Patients with a known sensitivity to any of the products to be administered during

treatment.

- Patients currently enrolled in another clinical trial or patients who have

participated in a trial of an investigational device or drug within the last 30 days.

- Patients previously treated with CPT-11.

- Concurrent stereotactic radiotherapy.

H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612, United States

Moffitt Cancer Center Clinical Trials Website

Starting date: February 2006
Ending date: March 2009
Last updated: March 20, 2008