Vitamin D for Treatment of Glioblastoma Multiforme

Glioblastoma Multiforme Clinical Trial

Official title:

High-Dose Vitamin D in Combination With Chemoradiotherapy in the Treatment of Glioblastoma Multiforme

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01181193
• Other study ID #: SOR504110CTIL
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: July 18, 2010
• Last updated: March 27, 2011
• Start date: March 2011
• Est. completion date: March 2014

Study information

• Verified date: August 2010
• Source: Soroka University Medical Center
• Contact: Konstantin Lavrenkov, MD, PhD
• Phone: +97286400537
• Email: constant[@]bgu.ac.il
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

This is non-randomized phase 2 study to assess efficacy and toxicity of long term high dose vitamin D3 given concurrently with chemo-radiotherapy (CCRT) containing temozolomide followed by adjuvant chemotherapy (ACT) with temozolomide in patients with newly diagnosed glioblastoma multiforme GBM). Preoperative diagnosis of GBM will be based on magnetic resonance imaging (MRI) brain scan. All patient will underwent craniotomy with partial or total resection of a visible tumour mass. All patients will be planned for postoperative three-dimensional conformal RT (3-DCRT) or intensity-modulated RT (IMRT) to residual tumour and/or resection bed. A total RT dose of 54-60 Gy will be delivered using 2 Gy daily fractions given over 5 days a week. Daily chemotherapy with temozolomide in the dose of 75 mg/m2/day will be started at the first day of RT, and will be continued for entire period of RT inclusive week-end breaks. ACT will contain 6 cycles of oral temozolomide 150-200 mg/m2/day given for 5 days every 4 weeks. Oral vitamin D3 will be administered in daily dose of 4000 IU. Vitamin D3 therapy will be started 1 week prior to commencing CCRT, and will be terminated immediately after completing last cycle of ACT. MRI scan of the brain will be performed at 4 months after completing CCRT, and than will be repeated every 4 months for first 2 years, and every 6 months for subsequent years. The study participants will be followed until disease progression or death. The study is expected to complete within 4 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: March 2014
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age > 18 years

2. Newly-diagnosed, histologically confirmed GBM

3. Surgical procedures: craniotomy with gross tumour resection or maximal debulking

4. Brain lesion suitable suitable for radical 3-DCRT/IMRT according to tumour location and size.

5. Karnofsky performance status (KPS) > 70 (ECOG/WHO 0-1)

6. No previous RT to brain

7. No serious comorbid condition

8. No treatment with biological response modifiers or cytotoxic agents within four weeks prior to study entry

9. No participation in clinical trial using any investigational drug or device within four weeks prior to study entry

10. No serious complication of malignant condition

11. No previous or concurrent malignancy at other sites, except cone biopsied in situ carcinoma of the uterine cervix and adequately treated basal cell or squamous cell carcinoma of the skin

12. Adequate organ function as evidenced by the following peripheral blood counts or serum chemistries at study entry:

• Hemoglobin > 9.0 Gm/dL

• WBC count > 4.0x109/L

• Neutrophile count > 1.5 cells x 109/L,

• Platelet count > 100 x 109/L,

• Creatinine < 1.5 mg/dL

• Total bilirubin < ULN (upper limit of normal)

• AST/SGOT < ULN

• Calcium < ULN

13. Ability to sign informed consent

14. Ability to attend follow-up visits

Exclusion Criteria:

1. Surgical procedures: only stereotactic biopsy

2. Brain lesion not suitable for 3-DCRT/IMRT

3. KPS < 70 (ECOG/WHO <2)

4. Previous RT to brain

5. Treatment with biological response modifiers or cytotoxic agents within four weeks prior to study entry

6. Participation in clinical trial using any investigational drug or device within 7 weeks prior to study entry

7. Major surgical procedure within two weeks prior to study entry

8. Serious comorbid condition, inclusive but not limited to myocardial infarction within previous six months, uncontrolled cardiac arrhythmias, uncontrolled angina pectoris, active infection including acute hepatitis

9. Serious complication of malignant condition

10. Previous or concurrent malignancy

11. Known hypersensitivity to vitamin D

12. Inadequate organ function as evidenced by the following peripheral blood counts or serum chemistries at study entry:

• Hemoglobin < 9.0 Gm/dL

• WBC count < 4.0x109/L

• Neutrophile count < 1.5 cells x 109/L,

• Platelet count < 100 x 109/L,

• Creatinine > 1.5 mg/dL

• Total bilirubin > ULN (upper limit of normal)

• AST/SGOT > ULN

• Calcium > ULN

13. Inability to sign informed consent

14. Psychological, familial, sociological or geographical conditions which do not permit regular medical follow-up and compliance with the protocol.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

Other:
• Surgery
Craniotomy with total or partial removal of the brain tumor

Radiation:
• Radiotherapy to tumour bed and/or residual tumour
60 Gy in 30 fractions over 6 weeks

Drug:
• Temozolomide
75 mg/m2/day for entire period of radiotherapy 150-200 mg/m2/day for 5 days every 28 days, 6 cycles total
• Vitamin D3
4000 IU started 1 week before commencing radiotherapy and discontinued immediately after completing last chemotherapy cycle

Locations

Country	Name	City	State
Israel	Soroka University Medical Center	Beer Sheva

Sponsors (1)

Lead Sponsor	Collaborator
Soroka University Medical Center

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival		long term	Yes
Secondary	Overall survival		long term	No