Brain and Central Nervous System Tumors, Cerebral Edema
Conditions
Keywords
cerebral edema, adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma
Brief summary
RATIONALE: Giving the herb Boswellia serrata after surgery and radiation therapy may slow the growth of any remaining tumor cells. It is not yet known whether giving Boswellia serrata together with standard treatment is more effective than standard treatment alone in treating high-grade gliomas. PURPOSE: This randomized phase II trial is the study of a combination of complementary and alternative medicine (CAM) herbal supplement intervention as an adjuvant to standard treatment of patients with newly diagnosed and recurrent high-grade gliomas (HGG). The central hypothesis of this application is that a herbal preparation that inhibits 5-LO activity, will produce measurable biologically meaningful decrease in 5-LO eicosanoid production and brain edema that will be associated with improved survival and quality of life in patients with HGG.
Detailed description
OBJECTIVES: Primary * To determine whether a herbal approach to decreasing 5-LO eicosanoid production reduces peritumoral brain edema in patients with HGG. Secondary * To determine if this adjuvant approach improves the quality of life and progression free and overall survival of patients with HGG. OUTLINE: This a randomized, controlled study. Patients are randomized to 1 of 2 treatment arms. * Arm I (intervention): Patients receive oral Boswellia serrata herbal extract 4 times a day and oral cyanocobalamin (vitamin B-12) once a day for 6 months in the absence of unacceptable toxicity. * Arm II (control): Patients receive oral vitamin B-12 once a day for 6 months. All patients are encouraged to eat a regular balanced diet (as recommended by the American Cancer Society for cancer prevention) with limited consumption of red and processed meats. Quality of life will be assessed at baseline and then at 2, 4, 6, 12, and 24 months. After completion of study treatment, patients will be followed every 6 months. PROJECTED ACCRUAL: A total of 70 patients (35 per treatment arm) will be accrued for this study.
Interventions
given orally
DIETARY_SUPPLEMENTcyanocobalamin
given orally
Sponsors
National Cancer Institute (NCI)
Ali Altunkaya
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients after surgical removal of histologically confirmed World Health Organization high-grade gliomas, including astrocytomas grade III (anaplastic astrocytoma), astrocytoma grade IV (glioblastoma multiforme, GBM), anaplastic oligodendroglioma and oligoastrocytoma * Karnofsky performance status of greater or equal 60 * Patients who signed informed consent * Patients can be receiving standard or investigational chemotherapy , hormonal therapy, immunotherapy or biologic agents as the primary treatment for their tumor * Glucocorticoid therapy is allowed * Bone marrow function (absolute neutrophil count \[ANC\] \>=1500/mm\^3 and platelet count \>=75,000/mm\^3); in the event of plate count dropping below 50,000/ mm\^3 the Boswellia will be withdrawn until plate count reaches 75,000 mm\^3 and above * Liver function (bilirubin and alkaline phosphatase =\< 2 x normal and serum glutamic oxaloacetic transaminase \[SGOT\] =\< 3 x normal) * Renal function (blood urea nitrogen \[BUN\] or creatinine =\< 1.5 x normal) * Patients suffering from mild to moderate asthma, liver and kidney disease; an assessment of the condition will be made to establish a baseline and monitor progress at 4 weekly intervals to start with for the first two months and thereafter at the usual study intervals of 4 and 6 months; if there is any significant deterioration in their condition the Boswellia will be withdrawn until these parameters are restored to their pre-treatment levels
Exclusion criteria
* Any medical condition that could interfere with eating and oral administration of B. serrata * Patients already taking herbal preparations that contain 5-LO inhibitors * Any previous (within the past 3 years) or concurrent malignancies at other sites, with the exception of surgically cured carcinoma-in-situ of the cervix and non-melanoma skin cancer * Pregnancy and breastfeeding * Active infection * Inability to be followed closely at the Cleveland Clinic Foundation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Peritumoral Brain Edema | at 4 months | The relative change from baseline will be assessed longitudinally, however, the main comparison of interest is the relative change at the 4-month evaluation.For each patient change = edema at follow up - baseline edema. |
| Change From Pooled Baseline in Peritumoral Brain Edema | at 2 months | The relative change from baseline will be assessed longitudinally, however, the main comparison of interest is the relative change at the 4-month evaluation. For each patient change = edema at follow up - baseline edema |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time-to-tumor-progression: Percentage of Patients With Tumor Progression at 6 Months | 6 months | Percentage of participants with tumor progression (\>25% increase in tumor volume compared to time 0) will be measured from enrollment to documented progression or death whichever comes first. The method used to calculate the time to tumor progression was Kaplan Meier test method to define the 95% confidence levels. |
| Overall Survival: Percentage of Patients That Were Alive at 1 Year | 1 year. | Overall survival will be measured from the date of enrollment to date of death or last contact. Survival will be evaluated by the Kaplan Meier method to evaluate the median survival and 1 year survival rates. |
| Time-to-tumor-progression: Percentage of Patients With Tumor Progression at 1 Year | 1 year | Percentage of participants with tumor progression (\>25% increase in tumor volume compared to time 0) will be measured from enrollment to documented progression or death whichever comes first. The method used to calculate the time to tumor progression was Kaplan Meier test method to define the 95% confidence levels. |
| Quality of Life at 6 Months | At 2, 4, 6, 12, and 24 months | Quality of life as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Items (EORTC QLQ-C30) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Food Intake as Assessed by the Block 98 Food Frequency Questionnaire and a 3-day Food Record | At 2, 4, 6, 12, and 24 months | The 3-day food diary will be used to assess the dietary intake and to increase eating awareness of patients. |
Countries
United States
Participant flow
Recruitment details
Patients recruited from September 2004-September 2010 from local medical clinic.
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Intervention) Patients receive oral Boswellia serrata extract 4 times a day and oral cyanocobalamin (vitamin B 12) once a day for 6 months in the absence of unacceptable toxicity.
cyanocobalamin : 50 ug/day given orally
Boswellia serrata extract : 4x (3-12.5) ml/day given orally, that is 720-3000mg of total Boswellic acids (three isomers)/day | 7 |
| Arm II (Control) Patients in the control arm receive oral cyanocobalamin (vitamin B 12) once a day for 6 months.
cyanocobalamin : 50 ug/daygiven orally | 5 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Difficult Travel Distance | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Arm I (Intervention) | Arm II (Control) | Total |
|---|---|---|---|
| Age, Customized 30-39 years | 1 participants | 0 participants | 1 participants |
| Age, Customized 40-49 years | 3 participants | 3 participants | 6 participants |
| Age, Customized 50-59 years | 1 participants | 2 participants | 3 participants |
| Age, Customized 60-69 years | 1 participants | 0 participants | 1 participants |
| Age, Customized 70-79 years | 1 participants | 0 participants | 1 participants |
| Baseline edema measure | 10.8 cm^3 STANDARD_DEVIATION 11.1 | 11.3 cm^3 STANDARD_DEVIATION 8.1 | 11.1 cm^3 STANDARD_DEVIATION 9.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 5 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 4 Participants | 11 Participants |
| Region of Enrollment United States | 7 participants | 5 participants | 12 participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 7 | 3 / 5 |
| serious Total, serious adverse events | 0 / 7 | 2 / 5 |
Outcome results
Primary
Change From Baseline in Peritumoral Brain Edema
The relative change from baseline will be assessed longitudinally, however, the main comparison of interest is the relative change at the 4-month evaluation.For each patient change = edema at follow up - baseline edema.
Time frame: at 4 months
Population: Patients with baseline and follow up peritumoral edema measurement. Closest measurement to time point was used. When 4 month was not available last prior was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Intervention) | Change From Baseline in Peritumoral Brain Edema | -2.7 cm^3 | Standard Deviation 7.3 |
| Arm II (Control) | Change From Baseline in Peritumoral Brain Edema | 10.21 cm^3 | Standard Deviation 14.06 |
p-value: 0.12t-test, 2 sided
Primary
Change From Baseline in Peritumoral Brain Edema
The relative change from baseline will be assessed longitudinally, however, the main comparison of interest is the relative change at the 4-month evaluation. For each patient change = edema at follow up - baseline edema.
Time frame: at 6 months
Population: Patients with baseline and follow up peritumoral edema measurement. Closest measurement to time point was used. When 4 month was not available last prior was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Intervention) | Change From Baseline in Peritumoral Brain Edema | -3.7 cm^3 | Standard Deviation 9.5 |
| Arm II (Control) | Change From Baseline in Peritumoral Brain Edema | -1.5 cm^3 | Standard Deviation 2.9 |
p-value: 0.8t-test, 2 sided
Primary
Change From Pooled Baseline in Peritumoral Brain Edema
The relative change from baseline will be assessed longitudinally, however, the main comparison of interest is the relative change at the 4-month evaluation. For each patient change = edema at follow up - baseline edema
Time frame: at 2 months
Population: Patients with baseline and follow up peritumoral edema measurement. Closest measurement to time point was used. When 4 month was not available last prior was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Intervention) | Change From Pooled Baseline in Peritumoral Brain Edema | -3.87 cm^3 | Standard Deviation 8 |
| Arm II (Control) | Change From Pooled Baseline in Peritumoral Brain Edema | -3.045 cm^3 | Standard Deviation 2.14 |
p-value: 0.9t-test, 2 sided
Secondary
Overall Survival: Percentage of Patients That Were Alive at 1 Year
Overall survival will be measured from the date of enrollment to date of death or last contact. Survival will be evaluated by the Kaplan Meier method to evaluate the median survival and 1 year survival rates.
Time frame: 1 year.
Population: All 12 patients followed to death or censored at last visit when known alive
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Intervention) | Overall Survival: Percentage of Patients That Were Alive at 1 Year | 57 percentage of particpants |
| Arm II (Control) | Overall Survival: Percentage of Patients That Were Alive at 1 Year | 60 percentage of particpants |
Secondary
Quality of Life at 6 Months
Quality of life as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Items (EORTC QLQ-C30)
Time frame: At 2, 4, 6, 12, and 24 months
Population: At baseline and the most recent post treatment point in time, the QOL data for group 1 consist of n=3 patients and for group 2, n=2. Because of low patient numbers, no analysis was done.
Secondary
Time-to-tumor-progression: Percentage of Patients With Tumor Progression at 1 Year
Percentage of participants with tumor progression (\>25% increase in tumor volume compared to time 0) will be measured from enrollment to documented progression or death whichever comes first. The method used to calculate the time to tumor progression was Kaplan Meier test method to define the 95% confidence levels.
Time frame: 1 year
Population: All 12 patients followed to progression or death, or censored at last visit when known alive
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Intervention) | Time-to-tumor-progression: Percentage of Patients With Tumor Progression at 1 Year | 71 percentage of participants |
| Arm II (Control) | Time-to-tumor-progression: Percentage of Patients With Tumor Progression at 1 Year | 80 percentage of participants |
Secondary
Time-to-tumor-progression: Percentage of Patients With Tumor Progression at 6 Months
Percentage of participants with tumor progression (\>25% increase in tumor volume compared to time 0) will be measured from enrollment to documented progression or death whichever comes first. The method used to calculate the time to tumor progression was Kaplan Meier test method to define the 95% confidence levels.
Time frame: 6 months
Population: All 12 patients followed to progression or death, or censored at last visit when known alive
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Intervention) | Time-to-tumor-progression: Percentage of Patients With Tumor Progression at 6 Months | 43 percentage of participants |
| Arm II (Control) | Time-to-tumor-progression: Percentage of Patients With Tumor Progression at 6 Months | 100 percentage of participants |
Other Pre-specified
Food Intake as Assessed by the Block 98 Food Frequency Questionnaire and a 3-day Food Record
The 3-day food diary will be used to assess the dietary intake and to increase eating awareness of patients.
Time frame: At 2, 4, 6, 12, and 24 months
Population: No data collected