Dietary, Herbal and Alternative Medicine in Glioblastoma Multiforme

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II Randomized Evaluation of 5-Lipoxygenase Inhibition by Herbal Complementary and Alternative Medicine Approach Compared to Control as an Adjuvant Therapy in Newly Diagnosed and Recurrent High-grade Gliomas

Conditions
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Brain and Central Nervous System Tumors, Cerebral Edema

Intervention / Treatment
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* Drug: Boswellia serrata extract
* Dietary Supplement: cyanocobalamin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (intervention)<br>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. | Drug: Boswellia serrata extract<br>* given orally<br>Dietary Supplement: cyanocobalamin<br>* given orally<br>* Other names: Vitamin B12;|
| Active Comparator: Arm II (control)<br>Patients in the control arm receive oral cyanocobalamin (vitamin B 12) once a day for 6 months. | Dietary Supplement: cyanocobalamin<br>* given orally<br>* Other names: Vitamin B12;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | at 2 months | 
| 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. | at 4 months | 
| 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. | at 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | At 2, 4, 6, 12, and 24 months | 
| 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. | 6 months | 
| 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. | 1 year | 
| 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. | 1 year. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cerebral edema, adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma