Thalidomide and Temozolomide or Camptothecin-11 (CPT-11) in Patients With Gliomas
Thalidomide and Temozolomide or Camptothecin-11 (CPT-11) in Patients With Gliomas
Objectives:

 1.1 To determine the efficacy, as measured by 6 month progression-free survival, of therapy
 with thalidomide combined with CPT-11 in the treatment of patients with recurrent and/or
 progressive malignant gliomas.

 1.2 To determine the rate of measureable clinical response in patients treated with
 Thalidomide and CPT-11.

 1.3 To determine Thrombotic thrombocytopenic purpura (TTP), overall survival and unexpected
 toxicity of Thalidomide and CPT-11 used in recurrent malignant gliomas.

 1.4 To determine changes in dynamic magnetic resonance imaging (MRI) as a surrogate marker
 for treatment effect.
Thalidomide is a drug that interferes with the growth of blood vessels. Thalidomide may help
 to decrease the blood supply in the tumor and make it unable to grow. CPT-11 is a drug that
 was designed to stop cancer cells from dividing.

 All participants will take thalidomide capsules by mouth every evening at bedtime. You will
 begin with 1 capsule every night for the first week then increase to 2 capsules every night
 for a week and then 3 capsules a night for the third week. After that, you will increase the
 dose to 4 capsules each night for the rest of the study. The dosages may be adjusted if you
 experience any severe side effects.

 In addition to thalidomide, you will receive treatment with CPT-11 through a continuous
 injection into a vein over 90 minutes once a week for 4 weeks followed by 2 weeks of rest
 from the drug. This 6 week period is called a course of therapy. The courses of therapy will
 be repeated as long as the disease is responding to treatment for up to 2 years.

 THIS IS AN INVESTIGATIONAL STUDY. Both drugs are commercially available. Thalidomide and
 CPT-11 are FDA approved for the treatment of some cancers. The combination of these drugs is
 investigational.

 Up to 78 participants will take part in this study. All will be enrolled at M. D. Anderson.
Is there an age limit? No

 Inclusion Criteria:

 1. Patients with histologically proven supratentorial malignant primary gliomas
 (Glioblastoma multiforme (GBM), Gliosarcoma (GS) Anaplastic astrocytoma (AA),
 Anaplastic oligodendroglioma (AO), mixed anaplastic glioma (MAG)) will be eligible for
 this protocol.

 2. Patients must have shown unequivocal evidence for tumor recurrence or progression by
 MRI scan after radiation therapy.

 3. Patients in the GBM stratum may have had treatment for no more than 2 prior relapses;
 for the AA stratum, there is no limitation for the number of relapses provided all
 other eligibility criteria particularly the functional status are met.

 4. All patients must sign an informed consent.

 5. The baseline on-study MRI should be performed within 14 days prior to registration and
 on a stable or decreasing steroid dosage.

 6. Patients having undergone recent resection of recurrent or progressive tumor will be
 eligible.

 7. Patients must have a life expectancy > 8 weeks.

 8. Patients must have a Karnofsky performance status of >= 70

 9. Patients must have recovered from the toxic effects of prior therapy: 4 weeks from
 prior cytotoxic therapy and/or at least two weeks from vincristine, 6 weeks from
 nitrosoureas, 3 weeks from procarbazine administration, and 1 week for non-cytotoxic
 agents, e.g., interferon, tamoxifen, cis-retinoic acid, etc. (radiosensitizer does not
 count). Patients who receive either Temozolomide or CPT-11 for non-therapeutic
 purposes (such as presurgically for obtaining pharmacology data for the agent) will be
 eligible for study entry provided they have recovered from the toxic effects of the
 agent if any.

 10. Patients must have adequate bone marrow function (Absolute neutrophil count (ANC)>
 1,500/mm3 and platelet count of > 100,000/mm3), adequate liver function (alanine
 aminotransferase (ALT or SGPT) and alkaline phosphatase <2 times normal, bilirubin
 <1.5 mg/dl), and adequate renal function (blood urea nitrogen (BUN) and creatinine
 <1.5 times institutional normal) prior to starting therapy.

 11. Patients must not be pregnant and must practice adequate contraception during the
 study and for 2 months after participation in study.

 Exclusion Criteria:

 1. 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.

 2. Patients must not have: a) active infection b) disease that will obscure toxicity or
 dangerously alter drug metabolism c) serious intercurrent medical illness. d) prior
 recurrence with CPT-11 (for the CPT-11 + Thalidomide arm) (prior treatment with
 thalidomide is permitted). e) grade 2 or higher peripheral neuropathy. Patients who
 have received Temozolomide or CPT-11 for non-therapeutic purposes (for eg., as part of
 a pharmacology study without therapeutic intent) will remain eligible for enrollment
 into the study.

 3. No exclusion to this study will be based on race. Minorities will actively be
 recruited to participate. The malignant glioma patient population treated at MDACC
 over the past year is as follows: American Indian or Alaskan Native - 0 Asian or
 Pacific Islander - <2% Black, not of Hispanic Origin - 3% Hispanic - 6% White, not of
 Hispanic Origin - 88% Other or Unknown - 2% Total-100%