This is a Phase I study of Nanoliposomal CPT-11 in patients with Recurrent high-grade
gliomas. Patients must have a histologically proven intracranial malignant glioma, which
includes glioblastoma multiforme (GBM), gliosarcoma (GS), anaplastic astrocytoma (AA),
anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant
astrocytoma NOS (not otherwise specified). Patients who are wild type or heterozygous for
the UGT1A1*28 gene will received Nanoliposomal CPT-11. The total anticipated accrual will be
approximately 36 patients (depending upon the actual MTD). The investigators hypothesis is
that this new formulation of CPT-11 will increase survival over that seen in historical
controls who have recurrent gliomas because CPT-11 will be encapsulated in a liposome
nanoparticle, which has been seen to reduce toxicities from the drug.
Patients with recurrent malignant glioma will receive Nanoliposomal CPT-11 at the time of
relapse. The dose will be adjusted according to a phase-1 dose escalation scheme. Patients
will receive drug intravenously every 3 weeks until tumor progression or excessive toxicity.
Weekly follow up will occur to assess toxicities during the DLT phase of the trial.
Patients will have different dose escalation if UGT1A1 is 6/6 versus UGT1A1 is 6/7.
Patients with UGT 1A1 of 7/7 will not be eligible. All patients must have UGT 1A1 status
know as an eligibility requirement. Patients will be followed for both toxicity and
progression, and progression will be evaluated by MR imaging every 6 weeks.
Pharmacokinetics will be obtained in the first treatment cycle.
- Patients with histologically proven intracranial malignant glioma are eligible .
-All patients must sign an informed consent
- 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
- 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) Patients must have shown
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. -Patients having undergone recent resection of recurrent
or progressive tumor will be eligible as long as all of the following conditions
- They have recovered from the effects of surgery.
- Residual disease following resection of recurrent malignant glioma is not
mandated for eligibility into the study.
- Patients must have failed prior radiation therapy
- Patients with prior therapy that included interstitial brachytherapy or stereotactic
radiosurgery must have confirmation of true progressive disease
- Women of childbearing potential must have a negative ß-HCG pregnancy test documented
within 14 days prior to registration.
- Patients may have had treatment for any number of prior relapses.
- Patients must not have any significant medical illnesses that in the investigator
opinion cannot be adequately controlled
- 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
- Patients must not have any disease that will obscure toxicity or dangerously alter
- 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