6-TG, Capecitabine and Celecoxib Plus TMZ or CCNU for Anaplastic Glioma Patients
Condition: Anaplastic Glioma of Brain; Glioblastoma Multiforme; Brain Cancer
MeSH terms: Glioblastoma; Glioma; Brain Neoplasms
Intervention: Capecitabine; Celecoxib (Celebrex); Temozolomide; Lomustine; 6-Thioguanine
Intervention description: Arms 1,3 = 825 mg/m^2 By Mouth (PO) Every 12 Hours on Day 14-27; Arms 2,3 = 825 mg/m^2 PO Every 12 Hours on Day 11-24.; Arms 1,3 = 400 mg PO Every 12 Hours On Day 14-27; Arms 2,3 = 400 mg PO Every 12 Hours On Day 11-24.; Arms 1,3 = 150 mg/m^2 PO Daily On Day 4-8.; Arms 2,3 = 100 mg/m^2 PO on Day 4.; Arms 1,2,3 = 80 mg/m^2 PO Every 6 Hours on Day 1-3.
Intervention MeSH terms: Celecoxib; Capecitabine; Thioguanine; Temozolomide; Lomustine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 75.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: Anaplastic Glioma; Glioblastoma Multiforme; Brain Cancer; 6-Thioguanine; Capecitabine; Celecoxib; Temozolomide; Xeloda; Temodar; TMZ; CCNU; 6-TG

Summary:

      The goal of this clinical research study is to learn if the combination of 6-Thioguanine,
      Xeloda (capecitabine), and Celebrex (celecoxib) with Temodar (temozolomide) or Lomustine
      (CCNU) is effective in the treatment of recurrent or progressive anaplastic glioma or
      glioblastoma multiforme in patients who have failed previous treatments. The safety of these
      combination treatment will also be studied.

      Objectives:

      1.1 To determine the efficacy, as measured by 12 month progression-free survival, of
      TEMOZOLOMIDE or CCNU with 6-THIOGUANINE followed by CAPECITABINE and CELECOXIB in the
      treatment of patients with recurrent and/or progressive anaplastic gliomas or glioblastoma
      multiforme.

      1.2 To determine the long-term toxicity of TEMOZOLOMIDE or CCNU with 6-THIOGUANINE followed
      by CAPECITABINE and CELECOXIB in recurrent anaplastic glioma or glioblastoma multiforme
      patients treated in this manner.

      1.3 To determine the clinical relevance of genetic subtyping tumors as a predictor of
      response to this chemotherapy and long term survival
    

Eligibility criteria:

        Inclusion Criteria:

          1. All patients must sign an informed consent indicating that they are aware of the
             investigational nature of this study in keeping with the policies of this hospital.

          2. Patients with histologically proven supratentorial anaplastic oligodendrogliomas,
             anaplastic mixed oligoastrocytomas anaplastic astrocytomas or glioblastoma multiforme.

          3. Patients must have unequivocal evidence for tumor recurrence or progression by MRI
             scan performed within 14 days prior to enrollment or documented recurrence by tumor
             resection. Patients must have received radiation therapy previously.

          4. Patients having undergone recent resection of recurrent or progressive tumor will be
             eligible as long as all the following conditions are met: a) Patients have recovered
             from the effects of surgery; b) Extent of residual disease (if present) has been
             documented by MRI performed no later than 72 hours after surgery or, if not possible,
             at least 4 weeks post-operative. Radiographic evidence of residual disease is not
             mandated for enrollment.

          5. The baseline on-study MRI is performed within 14 days of enrollment and on a steroid
             dosage that has been stable. If the steroid dose is increased between the date of
             imaging and the initiation of chemotherapy, a new baseline MRI is required on stable
             steroids for 7 days.

          6. Patients must be equal to or greater than 12 years old.

          7. Patients must have a Karnofsky performance status of equal to or greater than 60
             (Karnofsky Performance Scale; Appendix D).

          8. 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, thalidomide, cis-retinoic acid, etc.
             (radiosensitizer does not count). Any questions related to the definition of
             non-cytotoxic agents should be directed to the Study Chair.

          9. Patients must have adequate bone marrow function (ANC equal or greater than 1,500/mm3
             and platelet count of equal or greater than 100,000/mm3), adequate liver function
             (SGPT and alkaline phosphatase <2 times normal, bilirubin <1.5 mg%), and adequate
             renal function (BUN and creatinine <1.5 times institutional normal) prior to starting
             therapy.

        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 (1 year for localized prostate carcinoma
             treated by prostatectomy or irradiation) are ineligible.

          2. Patients of childbearing potential must not be pregnant or become pregnant.

          3. Patients must not have: a) active infection; b) disease that will obscure toxicity or
             dangerously alter drug metabolism; c) serious intercurrent medical illness; d) acute
             or chronic pulmonary disease, pulmonary embolus, hypertension, diabetes, metabolic
             syndrome, stroke, heart disease,myocardial infarction, angina, coronary angioplasty,
             congestive heart failure, or coronary bypass surgery; e) allergies to sulfa drugs; f)
             severe psychiatric illness; g) uncontrolled hypertension (i.e. ->135/>85 mm Hg) on
             three repeated measurements during the 6 weeks prior to enrollment on the study

          4. Patients must not have (continued): h) family history of premature coronary disease
             (i.e. - onset < 55 years of age); i) uncontrolled hypercholesteremia [low-density
             lipoprotein cholesterol (LDL-C >130]. Hypercholesteremia must be controlled for at
             least 3 months prior to enrollment on study; j) history of systemic lupus
             erythematous, family history of protein S or C deficiencies, prior heparin-induced
             thrombocytopenia, Factor V Leiden deficiencies or high homocysteine levels; k) any
             indications for ASA deficiency

          5. Patients must not have had prior treatment with Capecitabine, 5-FU or a combination of
             Temozolomide with CCNU (Lomustine) or BCNU (Carmustine). Patients who received only
             Temozolomide during radiation therapy and did not receive adjuvant chemotherapy with
             Temozolomide and/or those who received Gliadel (BCNU) wafers at surgery without
             adjuvant chemotherapy with BCNU or CCNU are eligible if 6 months has passed since the
             treatment(s).