Recruiting
Phase 2

Sunitinib, Temozolomide, Radiation

Sponsor:

Bassam Abdulkarim

Code:

NCT02928575

Conditions

Glioblastoma Multiforme

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

Interventions

Sunitinib

Temozolomide

Radiation Therapy

Study Details

Brief 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.

Conditions

Glioblastoma Multiforme

Study ID

NCT02928575

Start date

Aug, 2012

Status verified date

Oct, 2016

Completion date

Jun, 2017

Anticipated

Primary completion date

Dec, 2016

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Histologically documented newly diagnosed GBM patients
  • Unmethylated MGMT promoter as determined by Methylation specific-polymerase chain reaction (MGMT(+) tumor)
  • Age between 18 to 70
  • Karnofsky performance status ≥70
  • History and physical examination including neurologic examination within 4 weeks prior to registration
  • Systolic blood pressure ≤ 160 mmHg or diastolic pressure ≤ 100mm Hg
  • Required blood work within 14 days prior to registration
  • Eligible for standard concurrent chemoradiation with TMZ
  • Patients must have normal organ and marrow functions as defined below:

  • Absolute neutrophil count ≥ 1.5x 109/L
  • Platelets ≥100x 109/L
  • Hemoglobin ≥80g/L
  • International Normalized Ratio ≤1.3
  • Creatinine ≤1.5x \[upper limit of normal\] Or creatinine clearance ≥60 mL/min/1.73m2
  • Normal baseline thyroid function as measured by a thyrotropic-stimulating hormone within institutional normal limits
  • Adequate liver function: Alanine transaminase or Aspartate transaminase < 2 x upper limit of normal and bilirubin 1.6 mg/dL. No active bleeding or pathologic condition that carries high risk of bleeding (e.g. tumor involving major vessels or known varices)
  • Patients who have undergone resection must meet the following conditions:

  • Patients must have recovered from the effects of surgery and a minimum of 14 to 28 days must have elapsed from the day of surgery to day of registration. Day of registration is considered the first day of Sunitinib.
  • For stereotactic biopsy, a minimum of 14 days must have elapsed prior to registration
  • No prior RT to the brain, chemotherapy, or anti-angiogenic therapy
  • Estimated life expectancy of at least 6 months
  • Premenopausal women must have a negative human chorionic gonadotropin within 14 days prior to registration
  • The effects of Sunitinib on the developing human fetus is unknown. Women of childbearing potential and male participants must practice adequate contraception. Should a woman become pregnant or suspect she is pregnant during the study, she should inform her treating physician immediately.
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Histologically documented newly diagnosed GBM patients with methylated MGMT promoter
  • Serious medical conditions that might be aggravated by treatment, including but not limited to: myocardial infarction within 6 months, congestive heart failure, unstable angina, active cardiomyopathy, unstable ventricular arrhythmia, uncontrolled hypertension, uncontrolled psychotic disorders, serious infections, active peptic ulcer disease, active liver disease or cerebrovascular disease with previous stroke
  • Patients with a history of coagulopathy
  • Evidence of intratumoural or peritumoural hemorrhage deemed significant by the treating physician
  • ≥ 1+ proteinuria on two successive urine dipstick assessments
  • thrombolytic therapy within 4 weeks
  • Patient with prolonged of corrected QT interval of more than 450 msec in screening EKG will be excluded
  • Women who are pregnant or nursing
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to Sunitinib
  • Previous treatment with Sunitinib or other inhibitors of the vascular endothelial growth factor signalling axis
  • Bleeding disorders
  • Concurrent use of anticoagulant or antiplatelet drugs
  • Patients with any condition that impairs their ability to swallow Sunitinib (e.g. gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease).
  • HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Sunitinib. In addition, these patients are at increased risk of lethal infections when treated with bone marrow-suppressive therapy
  • Individuals with MRI non-compatible metal in the body, or unable to undergo MRI procedures.
  • Allergy to gadolinium
  • Patients with severe liver impairment will not be enrolled in this study.

Study Design

Enrollment

45 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Sunitinib, Temozolomide and 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. 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.

Interventions

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.

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 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.

Primary outcome measure

  • Tumor Response Rate [ Time Frame: 24 weeks ]

Central Contacts and Locations

Central contacts

Bassam Abdulkarim, MD PhD FRCPC

514-934-1934bassam.abdulkarim@mcgill.ca

Locations

Tom Baker Cancer Center and University of Calgary

Recruiting

Calgary, Alberta, Canada, T2N 4N2

Contacts

Jacob Easaw, MD PhD FRCPC

403-521-3446Jay.Easaw@albertahealthservices.ca

McGill University Health Centre

Recruiting

Montreal, Quebec, Canada, H4A 3J1

Contacts

Bassam Abdulkarim, MD PhD FRCPC

514-934-1934bassam.abdulkarim@mcgill.ca

More Information

Sponsor

Bassam Abdulkarim

Last update posted

Oct 10, 2016

Last verified

Oct, 2016

Keywords

  • Glioblastoma
  • Sunitinib
  • Temozolomide
  • Radiation Therapy,
  • MGMT
  • Biomarkers

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Bassam Abdulkarim on 2016-10-10.