A Phase I Trial of Nanoliposomal CPT-11 (NL CPT-11) in Patients With Recurrent High-Grade Gliomas
A Phase I Trial of Nanoliposomal CPT-11 (NL CPT-11) in Patients With Recurrent High-Grade Gliomas
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.
Inclusion Criteria:

 -  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 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.

 -  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.

 Exclusion Criteria:

 -  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
 contraception.

 -  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.