A Phase 2 interventional study of Sunitinib and Temozolomide in Glioblastoma Multiforme, sponsored by Bassam Abdulkarim. Status unknown at 2 sites in Canada. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2016-10-10.
Sponsored by Bassam Abdulkarim · Phase 2, Interventional, and Treatment
The purpose of this study is to determine whether a combination of Sunitinib, Temozolomide and Radiation Therapy would be effective in the treatment of newly diagnosed Glioblastoma patients harboring tumors with unmethylated MGMT promoter.
Glioblastoma multiforme (GBM), the most common primary brain tumor in adults is known for its highly invasive and angiogenic profile. Despite advances in different modalities of GBM treatment, the overall prognosis of GBM remains dismal. The current standard of care is Radiation Therapy (RT) at a dose of 60 Gy (30 fractions) for 6 weeks with concurrent Temozolomide (TMZ; 75 mg/m2 daily for 6 weeks) followed by adjuvant TMZ (150/200mg/m2 daily, for 5 of 28 days x 6 months). The DNA repair protein O6-methylguanine methyltransferase (MGMT) removes alkyl adducts at the O6 position of guanine and therefore counteracts the cytotoxic effects of alkylating agents such as TMZ. Thus, GBM patients harboring tumors with unmethylated MGMT promoter and increased MGMT protein expression do not derive benefit from TMZ treatment.
Sunitinib (Sutent, SU11248) is an oral multitargeted receptor tyrosine kinase (RTK) inhibitor with anti-angiogenic activities. Sunitinib has been approved by the FDA for the treatment of patients with gastrointestinal stromal tumors after disease progression on or intolerance to imatinib, for the treatment of patients with advanced renal cell carcinoma and for the treatment of patients with unresectable, locally advanced, or metastatic well-differentiated pancreatic neuroendocrine tumors (pNET). Previous pre-clinical data showed the efficacy of sunitinib in GBM. The investigators preclinical data highlighted the differential effect of sunitinib in GBM MGMT-positive tumors with a greater response to sunitinib in combination with RT and TMZ compared to MGMT-negative tumors.
In this phase II trial, Investigator will test the efficacy and the safety of combining Sunitinib with RT and TMZ in newly diagnosed GBM patients displaying tumors with unmethylated MGMT promoter. Based on the investigators preclinical findings, patients with MGMT (+) tumors (do not derive benefit from TMZ treatment) are more likely to respond to sunitinib-based therapy. MGMT promoter methylation will be therefore used as a biomarker for selection of newly diagnosed GBM patients enrolled in this study.
1,920 studies on the registry are indexed under Glioblastoma; 450 are open to participants now.
This study's planned enrollment of 45 is above the median of 36 across 1,618 interventional studies indexed under Glioblastoma.
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Patients must have normal organ and marrow functions as defined below:
Patients who have undergone resection must meet the following conditions:
Exclusion Criteria:
Before concurrent treatment, patients will receive sunitinib orally at a dose of 12.5 mg once daily for one week prior to radiation. Patients will then receive a concomitant treatment of sunitinib at a dose of 12.5 mg once daily along with temozolomide (75 mg/m2 daily) along with radiotherapy (60 Gy in 30 fractions) over a period of 6 weeks. This concurrent treatment of sunitinib, temozolomide and radiotherapy is followed by a 1 month break after which the adjuvant temozolomide treatment is administered at a dose of 150/200mg/m2 daily, for 5 of 28 days over a period of 6 months.
Drug: Sunitinib · Drug: Temozolomide · Radiation: Radiation Therapy
Before concurrent treatment, patients will receive sunitinib orally at a dose of 12.5 mg once daily for one week prior to radiation. Patients will then receive a concomitant treatment of sunitinib at a dose of 12.5 mg once daily along with temozolomide (75 mg/m2 daily) along with radiotherapy (60 Gy in 30 fractions) over a period of 6 weeks.
Also known as: Sutent (SU11248)
Temozolomide (75 mg/m2 daily) will be administered along with sunitinib (12.5 mg once daily) and radiotherapy (60 Gy in 30 fractions) over a period of 6 weeks. This concurrent treatment of sunitinib, temozolomide and radiotherapy is followed by a 1 month break after which the adjuvant temozolomide treatment is administered at a dose of 150/200mg/m2 daily, for 5 of 28 days over a period of 6 months.
Patients will receive a concomitant treatment of radiotherapy (60 Gy in 30 fractions), sunitinib (12.5 mg once daily) and temozolomide (75 mg/m2 daily) over a period of 6 weeks.
Tumor Response Rate
The primary endpoint of this study is tumor response rate and will be assessed using the Response Assessment in Neuro-Oncology criteria (RANO). Tumor response rate will be compared to standard of care in newly diagnosed Glioblastoma Multiforme.
Time frame: 24 weeks
Overall Survival
Time frame: at 6 month post treatment
Progression free survival
Time frame: 6 months post treatment
Biomarkers (Cytokines) response
PDGF, VEGF, sVEGF-R1 / R-2, basic fibroblast growth factor (bFGF), EGF, placental growth factor (PIGF), stromal cell-derived factor-1α (SDF-1), interleukin (IL) -1β, IL-6, IL-8, transforming growth factor α (TGF- α), angiopoietin 1 (Ang1), angiopoietin 2 (Ang2), and soluble Tek/Tie2 receptor (sTie2)
Time frame: at 6 months post treatment
Adverse Events
Investigator will assess long-term tolerance/toxicity of Sunitinib-based therapy. Toxicity will be scored using NCI Clinical Trials Criteria for Adverse Events (CTCAE) Version 3.0 (http://ctep.info.nih.gov/).
Time frame: Assessment of toxicity will continue until week 13 post-sunitinib
level of functioning
Will be measured using Eastern Cooperative Oncology Group (ECOG performance status) 0-5
Time frame: at 6 months post treatment
Increase use of corticosteroids
Increase in corticosteroid dosage by 50%; in the absence of other clinical explanations (such as pseudoprogression) may indicate tumour progression. Calling this evolution clinical tumour progression is at the investigator's discretion.
Time frame: at 6 months post treatment
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