Clinical trial NCT01181193: Vitamin D for Treatment of Glioblastoma Multiforme
Official title: High-Dose Vitamin D in Combination With Chemoradiotherapy in the Treatment of Glioblastoma Multiforme
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Glioblastoma Multiforme
Keywords: glioblastoma multiforme
chemoradiotherapy
vitamin D
Lead sponsor: Soroka University Medical Center
Sponsor class: OTHER
First posted: 2010-08-13
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Progression free survival
timeFrame: long term
Secondary outcomes:
measure: Overall survival
timeFrame: long term
Other outcomes:
Locations:
city: Beer Sheva
country: Israel
facility: Soroka University Medical Center
Study officials:
affiliation: Soroka University Miedical Center
name: Konstantin Lavrenkov, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: