Vitamin D for Treatment of Glioblastoma Multiforme

NCT ID: NCT01181193

Last Updated: 2011-03-29

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2014-03-31

Brief 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.

Conditions

Glioblastoma Multiforme

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Surgery

Craniotomy with total or partial removal of the brain tumor

Intervention Type: OTHER

Radiotherapy to tumour bed and/or residual tumour

60 Gy in 30 fractions over 6 weeks

Intervention Type: RADIATION

Temozolomide

1. 75 mg/m2/day for entire period of radiotherapy

2. 150-200 mg/m2/day for 5 days every 28 days, 6 cycles total

Intervention Type: DRUG

Vitamin D3

4000 IU started 1 week before commencing radiotherapy and discontinued immediately after completing last chemotherapy cycle

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Soroka University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Soroka University Medical Center

Principal Investigators

Konstantin Lavrenkov, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Soroka University Miedical Center

Locations

Soroka University Medical Center

Beersheba, , Israel

Site Status: RECRUITING

Countries

Israel

Central Contacts

Konstantin Lavrenkov, MD, PhD

Role: CONTACT

constant@bgu.ac.il

+97286400537

Olga Belochitski, MD

Role: CONTACT

olgab@clalit.org.il

+97286400537

Facility Contacts

Konstantin Lavrenkov, MD, PhD

Role: primary

constant@bgu.ac.il

+97286400537

Olga Belochitski, MD

Role: backup

olgab@clalit.org.il

+97286400537

Other Identifiers

SOR504110CTIL

Identifier Type: -

Identifier Source: org_study_id