Vitamin D for Treatment of Glioblastoma Multiforme

• ClinicalTrials.gov Identifier: NCT01181193
• Recruitment Status: Unknown
• First Posted: August 13, 2010
• Last Update Posted: March 29, 2011
• Sponsor: Soroka University Medical Center
• Information provided by: Soroka University Medical Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Glioblastoma Multiforme	Other: Surgery; Radiation: Radiotherapy to tumour bed and/or residual tumour; Drug: Temozolomide; Drug: Vitamin D3	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: High-Dose Vitamin D in Combination With Chemoradiotherapy in the Treatment of Glioblastoma Multiforme
• Study Start Date: March 2011
• Estimated Primary Completion Date: March 2013
• Estimated Study Completion Date: March 2014

Arms and Interventions

Intervention Details:

• 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
  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
• Drug: Vitamin D3
  4000 IU started 1 week before commencing radiotherapy and discontinued immediately after completing last chemotherapy cycle

Outcome Measures

Primary Outcome Measures :

1. Progression free survival [ Time Frame: long term ]

Secondary Outcome Measures :

1. Overall survival [ Time Frame: long term ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Konstantin Lavrenkov, MD, PhD; +97286400537; constant@bgu.ac.il

Contact: Olga Belochitski, MD; +97286400537; olgab@clalit.org.il

Locations

Israel

Soroka University Medical Center; Recruiting

Beer Sheva, Israel, 84101

Contact: Konstantin Lavrenkov, MD, PhD +97286400537 constant@bgu.ac.il

Contact: Olga Belochitski, MD +97286400537 olgab@clalit.org.il

Sub-Investigator: Vladimir Gavrilov, MD, PhD

Sub-Investigator: Olga Belochitski, MD

Sub-Investigator: Vladimir Merkin, MD

Sponsors and Collaborators

Soroka University Medical Center

Investigators

• Principal Investigator: Konstantin Lavrenkov, MD, PhD; Soroka University Miedical Center

More Information

• Responsible Party: Konstantin Lavrenkov, MD, PhD, Soroka University Medical Center
• ClinicalTrials.gov Identifier: NCT01181193
• Other Study ID Numbers: SOR504110CTIL
• First Posted: August 13, 2010
• Last Update Posted: March 29, 2011
• Last Verified: August 2010

Keywords provided by Soroka University Medical Center:

glioblastoma multiforme; chemoradiotherapy; vitamin D

Additional relevant MeSH terms:

Glioblastoma; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Vitamin D; Cholecalciferol; Temozolomide; Vitamins; Micronutrients; Nutrients; Growth Substances; Physiological Effects of Drugs; Bone Density Conservation Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Calcium-Regulating Hormones and Agents