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Combination of 6-Thioguanine, Capecitabine, Celecoxib and Temozolomide or CCNU for Recurrent Anaplastic Glioma and Glioblastoma Multiforme

Phase 2
12 Years
Not Enrolling
Anaplastic Glioma of Brain, Glioblastoma Multiforme, Brain Cancer

Thank you

Trial Information

Combination of 6-Thioguanine, Capecitabine, Celecoxib and Temozolomide or CCNU for Recurrent Anaplastic Glioma and Glioblastoma Multiforme

Capecitabine is a drug that damages the DNA (deoxyribonucleic acid) of tumor cells and
blocks the function of DNA and RNA (ribonucleic acid) of tumor cells. These actions help to
kill the tumor cells.

Celecoxib is a drug that may help to prevent the development of some types of cancer by
blocking a type of enzyme (COX-2) that is found in tumor cells.

Temozolomide and CCNU are the current standard treatment for malignant brain tumors. Both
drugs work by damaging the DNA (deoxyribonucleic acid) of tumor cells to kill these tumor

6-Thioguanine is a drug that helps to increase the effects of Temozolomide and CCNU on tumor

Depending on the previous treatment you have received, you will be treated according to Arms
1, 2, or 3.

If you have not received temozolomide before, you will be treated on Arm 1. If you have
received temozolomide before but only during radiation therapy and not as chemotherapy
afterwards and the treatment was over 6 months ago, you will be treated with temozolomide
according to Arm 1.

If you have not received lomustine or carmustine, you will be treated on Arm 2. If you have
received Gliadel wafers at surgery greater than 6 months ago and have not been treated with
lomustine or carmustine, you will be treated with CCNU according to Arm 2.

Arm 3 will include glioblastoma multiforme patients who may be treated with either
temozolomide or lomustine according to the above guidelines and regimens described in Arms 1
and 2.

Arm 1:

Treatment will begin with 6-thioguanine taken by mouth 4 times a day (every 6 hours) for 3
days in a row (Days 1-3). This will be followed by temozolomide taken by mouth at bedtime
for 5 days in a row (Days 4-8). After a rest period of 6 days, capecitabine and celecoxib
will be taken by mouth twice a day (12 hours apart) for 14 days (Days 14-27). Each cycle of
treatment on arm 1 will be 28 days.

Arm 2:

Treatment will begin with 6-thioguanine taken by mouth 4 times a day (every 6 hours) for 3
days in a row (Days 1-3). This will be followed by lomustine taken by mouth at bedtime for 1
day (Day 4). After a rest period of 1 week, capecitabine and celecoxib will be taken by
mouth twice a day (12 hours apart) for 14 days (Days 11-24). Each cycle of treatment on arm
2 will take 42 days.

Blood tests (less than 2 teaspoons) will be repeated every 2 weeks and before each new cycle
of treatment (a total of about 2 tablespoons). The neurological exam, anticonvulsant level
blood tests and the stool test for blood, will be repeated before every cycle on Arms 2 and
3 (CCNU) and before every 2 cycles on Arms 1 and 3 (temozolomide). Kidney function will be
evaluated from the blood tests before every other course. Patients taking anticoagulants
(coumadin, warfarin) will have procedures to test the clotting ability of the blood before
each cycle or more frequently if the doctor feels it is necessary.

Arm 3:

Glioblastoma Multiforme patients will be treated on Arm 3 which will include the drug
regimen from either Arm 1 or Arm 2.

Treatment on all arms will continue for 1 year as long as the tumor does not grow and any
side effects are tolerable. Treatment may continue beyond one year if your doctor feels it
is needed. During the study, you may not receive any other investigational drug or have any
other treatment for the cancer, including surgery.

This is an investigational study. All drugs used in this study are FDA approved and are
commercially available. A total of 140 patients will take part in this study. All patients
will be enrolled at M. D. Anderson.

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

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

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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

12 Month-progression-free Survival for Participants With Anaplastic Tumors

Outcome Description:

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.

Outcome Time Frame:

12 months

Safety Issue:


Principal Investigator

Charles Conrad, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

September 2003

Completion Date:

August 2010

Related Keywords:

  • Anaplastic Glioma of Brain
  • Glioblastoma Multiforme
  • Brain Cancer
  • Anaplastic Glioma
  • Glioblastoma Multiforme
  • Brain Cancer
  • 6-Thioguanine
  • Capecitabine
  • Celecoxib
  • Temozolomide
  • Xeloda
  • Temodar
  • TMZ
  • CCNU
  • 6-TG
  • Brain Neoplasms
  • Glioblastoma
  • Glioma



UT MD Anderson Cancer Center Houston, Texas  77030