Inclusion Criteria:

• Patients with histologically proven intracranial malignant glioma will be eligible for this protocol.

Malignant glioma include glioblastoma multiforme (GBM), Gliosarcoma (GS), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant astrocytoma NOS (not otherwise specified).

• All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must have signed an authorization for the release of their protected health information.

Patients must be registered in UCSF Cancer Center database prior to treatment with study drug.

• Patients must be > 18 years old, and with a life expectancy > 8 weeks.

• Patients must have a Karnofsky performance status of > 60.

  • Patients must have recovered from the toxic effects of prior therapy: 28 days from any investigational agent, 28 days from prior cytotoxic therapy, 14 days from vincristine, 42 days from nitrosoureas, 21 days from procarbazine administration, and 7 days for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count).
  • Patients must have adequate bone marrow function (WBC > 3,000/µl, ANC > 1,500/mm3, platelet count of > 100,000/mm3, and hemoglobin > 10 gm/dl), adequate liver function (SGOT and bilirubin < 2 times ULN), and adequate renal function (creatinine < 1.5 mg/dL and/or creatinine clearance > 60 cc/min) before starting therapy. These tests must be performed within 14 days prior to registration. Eligibility level for hemoglobin may be reached by transfusion. - -Patients must have shown unequivocal radiographic evidence for tumor progression by MRI or CT scan. A scan should be performed within 14 days prior to registration and on a steroid dose that has been stable for at least 5 days. If the steroid dose is increased between the date of imaging and registration a new baseline MR/CT is required. The same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement.
  • Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply:
• They have recovered from the effects of surgery.
• Residual disease following resection of recurrent malignant glioma is not mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, a CT/ MRI should be done no later than 96 hours in the immediate post-operative period or at least 4 weeks post-operatively, within 14 days prior to registration. If the 96-hour scan is more than 14 days before registration, the scan needs to be repeated.

If the steroid dose is increased between the date of imaging and registration, a new baseline MRI/CT is required on a stable steroid dosage for at least 5 days.

• Patients must have failed prior radiation therapy and must have an interval of greater than or equal to 42 days from the completion of radiation therapy to registration date.
• Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or Thallium scanning, MR spectroscopy or surgical documentation of disease.
• Women of childbearing potential must have a negative ß-HCG pregnancy test documented within 14 days prior to registration. Female patients of childbearing potential are those who are not either surgically sterile (having undergone hysterectomy and/or bilateral salpingoophorectomy) or at least 50 years old and have had no menses for at least 24 months.
• Patients may have had treatment for any number of prior relapses. Relapse is defined as progression following initial therapy (i.e. radiation+/- chemotherapy if that was used as initial therapy).

Exclusion Criteria:

• Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy
• Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.
• Patients must not have active infection or serious intercurrent medical illness.
• Patients must not be pregnant/breast feeding and must agree to practice adequate contraception. Patients must not be pregnant because animal studies show that NL CPT-11 is teratogenic.
• Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism.
• Patients must not have received prior therapy with irinotecan.
• Patients with 7/7 (homozygous) UGT1A1*28 genotyping will be excluded from the study.
• Patients receiving enzyme-inducing anticonvulsants or other enzyme inducing drugs are excluded.