Dietary, Herbal and Alternative Medicine in Glioblastoma Multiforme

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

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.

Study Overview

• Status: Terminated
• Conditions: Brain and Central Nervous System Tumors; Cerebral Edema
• Intervention / Treatment: Drug: Boswellia serrata extract; Dietary supplement: cyanocobalamin

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Boswellia serrata extract; given orally; Dietary supplement: cyanocobalamin; given orally; Other Names: Vitamin B12
Active Comparator: Arm II (control); Patients in the control arm receive oral cyanocobalamin (vitamin B 12) once a day for 6 months.	Dietary supplement: cyanocobalamin; given orally; Other Names: Vitamin B12

What is the study measuring?

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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At 2, 4, 6, 12, and 24 months

Collaborators and Investigators

• Sponsor: Ali Altunkaya
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Glen Stevens, DO, PhD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start: September 1, 2004
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: October 20, 2005
• First Submitted That Met QC Criteria: October 20, 2005
• First Posted (Estimate): October 21, 2005

Study Record Updates

• Last Update Posted (Actual): April 30, 2019
• Last Update Submitted That Met QC Criteria: April 21, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma; adult anaplastic astrocytoma; adult anaplastic oligodendroglioma; cerebral edema
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Nervous System Neoplasms; Central Nervous System Neoplasms; Brain Edema; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Hematinics; Vitamin B 12; Hydroxocobalamin
• Other Study ID Numbers: CASE1304; CCF-7348 (Other Identifier: Cleveland Clinic IRB); NCI-2010-01384 (Other Identifier: NCI/CTRP); R21CA107277-01 (U.S. NIH Grant/Contract)