Malignant Glioma
Conditions
Keywords
HGG, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed glioma, glioblastoma multiforme, GBM, Xeloda, capecitabine
Brief summary
The purpose of this study is to determine if capecitabine is effective in the treatment of high grade gliomas that have returned after completing treatment.
Detailed description
High grade gliomas (HGGs) represent a heterogenous group of primary brain tumors that share WHO grade III or IV classification (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed glioma, and glioblastoma multiforme). Despite the upfront use of surgery, radiation, and chemotherapy, high grade gliomas uniformly result in recurrence and death. Palliative chemotherapy offers an improvement in time to progression, symptom control, quality of life, and potential survival; however, no established chemotherapy regimen for recurrence exists and new treatments are needed. Oral capecitabine is a rationale strategy for therapeutic palliation of recurrent high grade gliomas given its oral administration, its well-known kinetics and toxicities, its non-competitive toxicities to other high grade glioma treatments, its well established management algorithms, its established evidence of entry into the central nervous system, and its evidence of safety and efficacy in malignancies in the central nervous system.
Interventions
DRUGCapecitabine
1,000-1,250 mg/m2 taken by mouth twice daily for 14 out of 21 consecutive days until progression or unacceptable toxicity.
Sponsors
University of Florida
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histological confirmation of high grade glioma (WHO grade III or IV: anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed glioma, and glioblastoma multiforme) * Male or female 18 years of age or older * Negative pregnancy test (if of childbearing potential) * Any number of previous recurrences will be allowed * Karnofsky Performance Status \> 60 * Hematocrit \> 30,000 * White blood cell count \> 1,500 * Platelet \> 100,000 * Absolute Neutrophil Count \> 1,000 * Bilirubin \< 1.5 x upper limits of normal * Transaminases (ALT and AST) \< 1.5 x upper limits of normal * Creatinine \< 1.5 x upper limits of normal * Adequate medical health to participate in this study * Adequate documentation of menopause (natural/surgical) or patient commitment to routine use of reliable birth control (barrier/hormonal) * Ability to read and understand the informed consent document * Ability and willingness to follow all requirements of the study including following all directions, taking medication as prescribed and completing all diaries and forms
Exclusion criteria
* Karnofsky Performance Status \< 60 * Hematocrit \< 30,000 * White blood cell count \< 1,500 * Platelet \< 100,000 * Absolute Neutrophil Count \< 1,000 * Bilirubin \>1.5 x upper limits of normal * Transaminases (ALT and AST) \> 1.5 x upper limits of normal * Creatinine \> 1.5 x upper limits of normal * Inability to undergo gadolinium-contrasted MRIs, including severe claustrophobia or insufficient allergy prophylaxis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Progression-free Survival. | From date of first dose of study drug until month 6. | Gadolinium-contrasted MRIs were used to assess radiographic response every 2 cycles (\ 6 weeks). Tumor progression was defined by increasing tumor size, new areas of tumor, or unequivocal neurologic deterioration. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the investigator's clinical practice from October 2008 thru June 2011.
Pre-assignment details
30 participants were enrolled in the study. 7 were excluded from participation prior to group assignment \[5 were unable to purchase study drug; 1 had rapid tumor growth; and, 1 was withdrawn by the investigator for mental health reasons\].
Participants by arm
| Arm | Count |
|---|---|
| Capecitabine Capecitabine (1,000-1,250 mg/m2) was taken by mouth twice daily for 14 out of 21 consecutive days until disease progression or unacceptable toxicity. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
| Overall Study | Tumor Progression | 1 |
| Overall Study | Unable to purchase study drug | 5 |
Baseline characteristics
| Characteristic | Capecitabine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants |
| Age Continuous | 51.5 years STANDARD_DEVIATION 12.6 |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 23 / 23 |
| serious Total, serious adverse events | 21 / 23 |
Outcome results
Primary
Percentage of Participants With Progression-free Survival.
Gadolinium-contrasted MRIs were used to assess radiographic response every 2 cycles (\ 6 weeks). Tumor progression was defined by increasing tumor size, new areas of tumor, or unequivocal neurologic deterioration.
Time frame: From date of first dose of study drug until month 6.
Population: Per protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Capecitabine | Percentage of Participants With Progression-free Survival. | 21.7 percentage of participants with PFS6 |
95% CI: [7.46, 43.7]