Combining Sunitinib, Temozolomide and Radiation to Treat Patients Diagnosed With Glioblastoma

Official Title

A Phase II Trial of Concurrent Sunitinib, Temozolomide and Radiation Therapy Followed by Adjuvant Temozolomide for Newly Diagnosed Glioblastoma Patients With an Unmethylated MGMT Gene Promoter

Summary:

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 tumours with unmethylated MGMT promoter.

Trial Description

Primary Outcome:

  • Tumour Response Rate
Secondary Outcome:
  • Overall Survival
  • Progression free survival
  • Biomarkers (Cytokines) response
  • Adverse Events
  • level of functioning
  • Increase use of corticosteroids
Glioblastoma multiforme (GBM), the most common primary brain tumour 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 tumours 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 tumours 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 tumours (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 tumours with a greater response to sunitinib in combination with RT and TMZ compared to MGMT-negative tumours. 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 tumours with unmethylated MGMT promoter. Based on the investigators preclinical findings, patients with MGMT (+) tumours (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.

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society