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

Sponsor:	M.D. Anderson Cancer Center
Information provided by:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00504660

Purpose

Primary Objectives:

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.
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.
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 Glioblastoma Multiforme Brain Cancer	Drug: Capecitabine Drug: Celecoxib Drug: Temozolomide Drug: Lomustine Drug: 6-Thioguanine	Phase II

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

Resource links provided by NLM:

MedlinePlus related topics: Brain Cancer Cancer Childhood Brain Tumors

Drug Information available for: Lomustine Temozolomide Capecitabine Celecoxib Thioguanine

U.S. FDA Resources

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

Primary Outcome Measures:

Progression-free Survival (PFS) [ Time Frame: 6 months and 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	140
Study Start Date:	September 2003
Estimated Primary Completion Date:	September 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Anaplastic Tumors: Active Comparator Anaplastic Tumors - 6-TG, Temozolomide, Capecitabine and Celebrex	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. Drug: Celecoxib 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. Drug: Temozolomide Arms 1,3 = 150 mg/m^2 PO Daily On Day 4-8. Drug: 6-Thioguanine Arms 1,2,3 = 80 mg/m^2 PO Every 6 Hours on Day 1-3.
2: Anaplastic Tumors: Active Comparator Anaplastic Tumors - 6-TG, Lomustine, Capecitabine and Celebrex	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. Drug: Celecoxib 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. Drug: Lomustine Arms 2,3 = 100 mg/m^2 PO on Day 4. Drug: 6-Thioguanine Arms 1,2,3 = 80 mg/m^2 PO Every 6 Hours on Day 1-3.
3: Glioblastoma Multiforme: Active Comparator Glioblastoma Multiforme - 6-TG, Temozolomide, Capecitabine and Celebrex or 6-TG, Lomustine, Capecitabine and Celebrex	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. Drug: Celecoxib 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. Drug: Temozolomide Arms 1,3 = 150 mg/m^2 PO Daily On Day 4-8. Drug: Lomustine Arms 2,3 = 100 mg/m^2 PO on Day 4. Drug: 6-Thioguanine Arms 1,2,3 = 80 mg/m^2 PO Every 6 Hours on Day 1-3.

Hide Detailed Description

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.

Before treatment starts, you will have a complete physical and neurological examination. A neurological examination includes a checkup by a physician on the eye movements, range of vision, facial muscles, speech, gait and strength, and coordination and sensation of the arms and legs (functions of the nervous system). Blood (about 2 tablespoons) will be taken for routine tests and about 1 tablespoon to test the level of anticonvulsants in the blood. A check on the anticonvulsant levels is routine in patients with brain tumors. A MRI scan of the brain will be done. For this MRI, a special dye will be injected into a vein to highlight the tumor. Women who are able to have children must have a negative blood pregnancy test. A stool test will be done to look for any blood. Patients with a history of ulcers or other stomach problems may have additional tests such as an endoscopy or barium studies. Endoscopy involves having a fiberoptic camera device inserted through the mouth into the stomach to view the inside of the stomach and part of the small intestines. Barium studies involve swallowing a liquid to coat the surface of the stomach followed by x-rays to view the outline of the stomach.

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.

Eligibility

Ages Eligible for Study:	12 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.
Patients with histologically proven supratentorial anaplastic oligodendrogliomas, anaplastic mixed oligoastrocytomas anaplastic astrocytomas or glioblastoma multiforme.
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.
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.
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.
Patients must be equal to or greater than 12 years old.
Patients must have a Karnofsky performance status of equal to or greater than 60 (Karnofsky Performance Scale; Appendix D).
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.
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:

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.
Patients of childbearing potential must not be pregnant or become pregnant.
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
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
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

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

Locations

United States, Texas
U.T.M.D. Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Investigators

Principal Investigator:

Victor Levin, MD

U.T.M.D. Anderson Cancer Center

More Information

Additional Information:

U.T. M.D. Anderson's website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	U.T.M.D. Anderson Cancer Center ( Victor Levin, MD/Professor )
Study ID Numbers:	2003-0600
Study First Received:	July 18, 2007
Last Updated:	June 29, 2009
ClinicalTrials.gov Identifier:	NCT00504660 History of Changes
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:

Anti-Inflammatory Agents
Antimetabolites
Glioblastoma
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Neoplasms, Nerve Tissue
Lomustine
Central Nervous System Neoplasms
6-Mercaptopurine
Brain Diseases
Neoplasms by Site
Sensory System Agents

Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Glioma
Alkylating Agents
Nucleic Acid Synthesis Inhibitors
Nervous System Neoplasms
Capecitabine
Neoplasms by Histologic Type
Celecoxib
Astrocytoma
Cyclooxygenase Inhibitors
Nervous System Diseases
Thioguanine

ClinicalTrials.gov processed this record on November 27, 2009