Thalidomide and Temozolomide or Camptothecin-11 (CPT-11) in Patients With Gliomas
Condition: Glioblastoma Multiforme; Glioma
MeSH terms: Glioblastoma; Glioma
Intervention: Thalidomide; CPT-11; MRI Scan; Quantitative Sensory Tests (QST)
Intervention description: 100 mg PO (by mouth) daily for 8 weeks; 125 mg/m^2 by vein weekly over 90 minutes for 4 weeks, followed by 2 weeks rest; Dynamic MRI scan with dye injection through vein, every 6 weeks; QST, every 12 weeks, to check for any nerve problems that may be present before starting treatment; by touching a small machine tests are done on feeling of touch, vibration, and temperature.
Intervention MeSH terms: Thalidomide; Irinotecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 78.0
Sex: All
Healthy volunteers: No
Keywords: Glioblastoma Multiforme; Glioma; Thalidomide; Thalomid; CPT-11; Irinotecan; malignant glioma

Summary:

      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.
    

Eligibility criteria:

        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%