NCT02928575

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

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

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Sponsor: Bassam Abdulkarim · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

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 tumors with unmethylated MGMT promoter.

Detailed description

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.

Conditions

• Glioblastoma Multiforme

Interventions

Type	Name	Description
DRUG	Sunitinib	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.
DRUG	Temozolomide	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.
RADIATION	Radiation Therapy	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.

Timeline

• Start date: 2012-08-01
• Primary completion: 2016-12-01
• Completion: 2017-06-01
• First posted: 2016-10-10
• Last updated: 2016-10-10

Locations

2 sites across 1 country: Canada