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CompletedNCT00504660Updated Jan 11, 2012Results posted

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

A Phase 2 interventional study of Capecitabine and Celecoxib (Celebrex) in Anaplastic Glioma of Brain, Glioblastoma Multiforme and Brain Cancer, sponsored by M.D. Anderson Cancer Center. Completed at 1 site in United States. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2012-01-11.

Sponsored by M.D. Anderson Cancer Center · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
75
Allocation
Non-randomized
Ages
12 Years and older
Sex
All
01

Study 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

Read the detailed description

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 cells.

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

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.

02

Conditions studied

  • Anaplastic Glioma of Brain
  • Glioblastoma Multiforme
  • Brain Cancer

Keywords

  • Anaplastic Glioma
  • Glioblastoma Multiforme
  • Brain Cancer
  • 6-Thioguanine
  • Capecitabine
  • Celecoxib
  • Temozolomide
  • Xeloda
  • Temodar
  • TMZ
  • CCNU
  • 6-TG
03

In context

Glioblastoma

1,920 studies on the registry are indexed under Glioblastoma; 450 are open to participants now.

This study's enrollment of 75 is above the median of 36 across 1,618 interventional studies indexed under Glioblastoma.

Browse Glioblastoma studies →

Lead sponsor

M.D. Anderson Cancer Center is the lead sponsor of 2,999 studies on the registry; 581 are open to participants now.

Of its 599 completed or terminated interventional studies of FDA-regulated products, 402 (67%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
12 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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).
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
75 participants (actual)

Study arms

  • 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 · Drug: Celecoxib (Celebrex) · Drug: Temozolomide · Drug: 6-Thioguanine

  • 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 · Drug: Celecoxib (Celebrex) · Drug: Lomustine · Drug: 6-Thioguanine

  • 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 · Drug: Celecoxib (Celebrex) · Drug: Temozolomide · Drug: Lomustine · Drug: 6-Thioguanine

Interventions

  • DrugCapecitabine

    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.

    Also known as: Xeloda

  • DrugCelecoxib (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.

    Also known as: Celebrex

  • DrugTemozolomide

    Arms 1,3 = 150 mg/m\^2 PO Daily On Day 4-8.

    Also known as: Temodar, TMZ

  • DrugLomustine

    Arms 2,3 = 100 mg/m\^2 PO on Day 4.

    Also known as: CCNU

  • Drug6-Thioguanine

    Arms 1,2,3 = 80 mg/m\^2 PO Every 6 Hours on Day 1-3.

    Also known as: Thioguanine, 6-TG

06

What researchers measure

Primary outcomes

  1. 12 Month-progression-free Survival for Participants With Anaplastic Tumors

    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.

    Time frame: 12 months

  2. 6 Month Progression-free Survival for Participants With Glioblastoma

    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.

    Time frame: 6 months

07

Results

Posted Jan 11, 2012

Participant flow

Recruitment period: September 23, 2003 to June 15, 2009. All patients recruited at UT MD Anderson Cancer Center.

Participant flow — Overall Study
MilestoneAnaplastic TumorsGlioblastoma Multiforme
Started3143
Completed3143
Not completed00

Outcome measures

Primary12 Month-progression-free Survival for Participants With Anaplastic Tumors

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.

Time frame:
12 months
Reported as:
Number · percentage of participants
12 Month-progression-free Survival for Participants With Anaplastic Tumors
percentage of participantsParticipants With Recurrent Anaplastic Glioma
12 Month-progression-free Survival for Participants With Anaplastic Tumors44 ± 5
Primary6 Month Progression-free Survival for Participants With Glioblastoma

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.

Time frame:
6 months
Reported as:
Number · percentage of participants
6 Month Progression-free Survival for Participants With Glioblastoma
percentage of participantsParticipants With Glioblastoma Multiforme
6 Month Progression-free Survival for Participants With Glioblastoma14

Adverse events

Collected over 6 years and 3 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Anaplastic Tumors—8/31 (25.8%)31/31 (100%)
Glioblastoma Multiforme—16/43 (37.2%)43/43 (100%)
Most frequent serious events
Showing 10 of 18
Most frequent serious events
EventAnaplastic TumorsGlioblastoma Multiforme
Thrombosis/EmbolismVascular disorders1/315/43
VomitingGastrointestinal disorders1/313/43
Muscle WeaknessMusculoskeletal and connective tissue disorders1/312/43
DiarrheaGastrointestinal disorders1/312/43
NauseaGastrointestinal disorders1/312/43
SeizureNervous system disorders1/311/43
HemorrhageGeneral disorders1/311/43
PneumonitisInfections and infestations1/310/43
Pain-BackMusculoskeletal and connective tissue disorders1/311/43
ThrombocytopeniaBlood and lymphatic system disorders1/310/43
Most frequent other events
Showing 10 of 40
Most frequent other events
EventAnaplastic TumorsGlioblastoma Multiforme
HYPERGLYCEMIAMetabolism and nutrition disorders14/3143/43
FATIGUEGeneral disorders24/3130/43
HEMOGLOBINBlood and lymphatic system disorders24/3133/43
LEUKOCYTESBlood and lymphatic system disorders21/3133/43
LYMPHOPENIABlood and lymphatic system disorders21/3133/43
PLATELETSBlood and lymphatic system disorders23/3131/43
NEUTROPHILS (ANC/AGC)Blood and lymphatic system disorders15/3128/43
MUSCLE WEAKNESSMusculoskeletal and connective tissue disorders10/3126/43
NAUSEAGastrointestinal disorders16/3116/43
CONSTIPATIONGastrointestinal disorders15/3115/43

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Anaplastic TumorsGlioblastoma MultiformeTotal
<=18 years000
Between 18 and 65 years293463
>=65 years2911
Sex: Female, Male
Sex: Female, Male(Participants)Anaplastic TumorsGlioblastoma MultiformeTotal
Female141529
Male172845
Region of Enrollment
Region of Enrollment(participants)Anaplastic TumorsGlioblastoma MultiformeTotal
United States314374
08

Study locations

1 site
  • UT MD Anderson Cancer Center
    Houston, Texas 77030, United States
09

References and documents

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 11, 2012, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00504660
Lead sponsor
M.D. Anderson Cancer Center
Responsible party
Sponsor
First posted
Jul 20, 2007
Start date
Sep 2003
Primary completion
Aug 2010
Completion
Aug 2010
Results posted
Jan 11, 2012
Last update
Jan 11, 2012

Study contacts

Charles Conrad, MD
principal investigator · UT MD Anderson Cancer Center

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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