6-TG, Capecitabine and Celecoxib Plus TMZ or CCNU for Anaplastic Glioma Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00504660
First received: July 18, 2007
Last updated: December 6, 2011
Last verified: December 2011
  Purpose

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


Condition Intervention Phase
Anaplastic Glioma of Brain
Glioblastoma Multiforme
Brain Cancer
Drug: Capecitabine
Drug: Celecoxib (Celebrex)
Drug: Temozolomide
Drug: Lomustine
Drug: 6-Thioguanine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Combination of 6-Thioguanine, Capecitabine, Celecoxib and Temozolomide or CCNU for Recurrent Anaplastic Glioma and Glioblastoma Multiforme

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • 12 Month-progression-free Survival for Participants With Anaplastic Tumors [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Progression-free Survival (PFS) at 12 months measured as percentage of participants that are alive and progression-free at 12 months (anaplastic tumors). A combination of neurological examination and MRI brain scan used to define overall response or progression.

  • 6 Month Progression-free Survival for Participants With Glioblastoma [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Progression-free Survival (PFS) at 6 months measured as percentage of participants that are alive and progression-free at 6 months (glioblastoma multiforme). A combination of neurological examination and MRI brain scan used to define overall response or progression.


Enrollment: 75
Study Start Date: September 2003
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1: Anaplastic Tumors
Anaplastic Tumors - 6-TG 80 mg/m^2 orally (PO) every 6 hours Day 1-3; Temozolomide 150 mg/m^2 PO daily Days 4-8, after 6 day rest Capecitabine 825 mg/m^2 and Celebrex 400 mg PO every 12 hours Day 14-27 for 28 day course.
Drug: Capecitabine
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.
Other Name: Xeloda
Drug: Celecoxib (Celebrex)
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.
Other Name: Celebrex
Drug: Temozolomide
Arms 1,3 = 150 mg/m^2 PO Daily On Day 4-8.
Other Names:
  • Temodar
  • TMZ
Drug: 6-Thioguanine
Arms 1,2,3 = 80 mg/m^2 PO Every 6 Hours on Day 1-3.
Other Names:
  • Thioguanine
  • 6-TG
Active Comparator: 2: Anaplastic Tumors

Anaplastic Tumors - 6-TG 80 mg/m^2 PO every 6 hours Day 1-3, Lomustine 100 mg/m^2 PO on Day 4; Capecitabine 825 mg/m^2 PO every 12 hours Days 11-24, and Celebrex 400 mg PO every 12 hours Days 11-24.

Participants if previously received Temozolomide but not Lomustine (CCNU) will receive Lomustine; or if had Gliadel wafers and Temozolomide with radiotherapy (XRT) will receive Temozolomide.

Drug: Capecitabine
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.
Other Name: Xeloda
Drug: Celecoxib (Celebrex)
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.
Other Name: Celebrex
Drug: Lomustine
Arms 2,3 = 100 mg/m^2 PO on Day 4.
Other Name: CCNU
Drug: 6-Thioguanine
Arms 1,2,3 = 80 mg/m^2 PO Every 6 Hours on Day 1-3.
Other Names:
  • Thioguanine
  • 6-TG
Active Comparator: 3: Glioblastoma Multiforme

Glioblastoma Multiforme - 6-TG 80 mg/m^2 PO every 6 Hours Day 1-3; Capecitabine 825 mg/m^2 PO every 12 hours Days 14-27 and Celebrex 400 mg PO every 12 hours Day 11-24; Temozolomide 150 mg/m^2 PO daily Days 4-8 OR CCNU (Lomustine) 100 mg/m2 orally Day 4 of each 42-day cycle.

Participants receive Temozolomide if not had previous treatment and if had prior CCNU. Those previously treated with Temozolomide but not CCNU receive CCNU, and those that had Gliadel and Temozolomide with XRT receive Temozolomide.

Drug: Capecitabine
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.
Other Name: Xeloda
Drug: Celecoxib (Celebrex)
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.
Other Name: Celebrex
Drug: Temozolomide
Arms 1,3 = 150 mg/m^2 PO Daily On Day 4-8.
Other Names:
  • Temodar
  • TMZ
Drug: Lomustine
Arms 2,3 = 100 mg/m^2 PO on Day 4.
Other Name: CCNU
Drug: 6-Thioguanine
Arms 1,2,3 = 80 mg/m^2 PO Every 6 Hours on Day 1-3.
Other Names:
  • Thioguanine
  • 6-TG

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00504660

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Charles Conrad, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00504660     History of Changes
Other Study ID Numbers: 2003-0600
Study First Received: July 18, 2007
Results First Received: December 6, 2011
Last Updated: December 6, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Anaplastic Glioma
Glioblastoma Multiforme
Brain Cancer
6-Thioguanine
Capecitabine
Celecoxib
Temozolomide
Xeloda
Temodar
TMZ
CCNU
6-TG

Additional relevant MeSH terms:
Brain Neoplasms
Glioblastoma
Glioma
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Lomustine
Temozolomide
Dacarbazine
Capecitabine
Thioguanine
Fluorouracil
Celecoxib
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 29, 2014