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

NCT02928575 | Unknown Phase 2

• 1 other identifier: McG 1132
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  24 weeks

Secondary Outcomes (6)

• Overall Survival

  at 6 month post treatment

• Progression free survival

  6 months post treatment

• Biomarkers (Cytokines) response

  at 6 months post treatment

• Adverse Events

  Assessment of toxicity will continue until week 13 post-sunitinib

• level of functioning

  at 6 months post treatment

Study Arms (1)

Sunitinib, Temozolomide and Radiation Therapy

EXPERIMENTAL

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

Interventions

Sunitinib DRUG

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)

Sunitinib, Temozolomide and Radiation Therapy

Temozolomide DRUG

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.

Sunitinib, Temozolomide and Radiation Therapy

Radiation Therapy RADIATION

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.

Sunitinib, Temozolomide and Radiation Therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bassam Abdulkarim: lead
• Pfizer: collaborator
• Canadian Cancer Society (CCS): collaborator

Study Sites (2)

Tom Baker Cancer Center and University of Calgary

Calgary, Alberta, T2N 4N2, Canada

RECRUITING

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Related Publications (14)

• Motzer RJ, Michaelson MD, Rosenberg J, Bukowski RM, Curti BD, George DJ, Hudes GR, Redman BG, Margolin KA, Wilding G. Sunitinib efficacy against advanced renal cell carcinoma. J Urol. 2007 Nov;178(5):1883-7. doi: 10.1016/j.juro.2007.07.030. Epub 2007 Sep 17.

  PMID: 17868732 BACKGROUND

• Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):115-24. doi: 10.1056/NEJMoa065044.

  PMID: 17215529 BACKGROUND

• Motzer RJ, Bukowski RM. Targeted therapy for metastatic renal cell carcinoma. J Clin Oncol. 2006 Dec 10;24(35):5601-8. doi: 10.1200/JCO.2006.08.5415.

  PMID: 17158546 BACKGROUND

• Motzer RJ, Rini BI, Bukowski RM, Curti BD, George DJ, Hudes GR, Redman BG, Margolin KA, Merchan JR, Wilding G, Ginsberg MS, Bacik J, Kim ST, Baum CM, Michaelson MD. Sunitinib in patients with metastatic renal cell carcinoma. JAMA. 2006 Jun 7;295(21):2516-24. doi: 10.1001/jama.295.21.2516.

  PMID: 16757724 BACKGROUND

• Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, McArthur G, Judson IR, Heinrich MC, Morgan JA, Desai J, Fletcher CD, George S, Bello CL, Huang X, Baum CM, Casali PG. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006 Oct 14;368(9544):1329-38. doi: 10.1016/S0140-6736(06)69446-4.

  PMID: 17046465 BACKGROUND

• Faivre S, Delbaldo C, Vera K, Robert C, Lozahic S, Lassau N, Bello C, Deprimo S, Brega N, Massimini G, Armand JP, Scigalla P, Raymond E. Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol. 2006 Jan 1;24(1):25-35. doi: 10.1200/JCO.2005.02.2194. Epub 2005 Nov 28.

  PMID: 16314617 BACKGROUND

• de Bouard S, Herlin P, Christensen JG, Lemoisson E, Gauduchon P, Raymond E, Guillamo JS. Antiangiogenic and anti-invasive effects of sunitinib on experimental human glioblastoma. Neuro Oncol. 2007 Oct;9(4):412-23. doi: 10.1215/15228517-2007-024. Epub 2007 Jul 10.

  PMID: 17622648 BACKGROUND

• Abdollahi A, Lipson KE, Sckell A, Zieher H, Klenke F, Poerschke D, Roth A, Han X, Krix M, Bischof M, Hahnfeldt P, Grone HJ, Debus J, Hlatky L, Huber PE. Combined therapy with direct and indirect angiogenesis inhibition results in enhanced antiangiogenic and antitumor effects. Cancer Res. 2003 Dec 15;63(24):8890-8.

  PMID: 14695206 BACKGROUND

• Frederick B, Gustafson D, Bianco C, Ciardiello F, Dimery I, Raben D. ZD6474, an inhibitor of VEGFR and EGFR tyrosine kinase activity in combination with radiotherapy. Int J Radiat Oncol Biol Phys. 2006 Jan 1;64(1):33-7. doi: 10.1016/j.ijrobp.2005.05.050.

  PMID: 16377413 BACKGROUND

• Huber PE, Bischof M, Jenne J, Heiland S, Peschke P, Saffrich R, Grone HJ, Debus J, Lipson KE, Abdollahi A. Trimodal cancer treatment: beneficial effects of combined antiangiogenesis, radiation, and chemotherapy. Cancer Res. 2005 May 1;65(9):3643-55. doi: 10.1158/0008-5472.CAN-04-1668.

  PMID: 15867359 BACKGROUND

• Schueneman AJ, Himmelfarb E, Geng L, Tan J, Donnelly E, Mendel D, McMahon G, Hallahan DE. SU11248 maintenance therapy prevents tumor regrowth after fractionated irradiation of murine tumor models. Cancer Res. 2003 Jul 15;63(14):4009-16.

  PMID: 12873999 BACKGROUND

• Siemann DW, Rojiani AM. The vascular disrupting agent ZD6126 shows increased antitumor efficacy and enhanced radiation response in large, advanced tumors. Int J Radiat Oncol Biol Phys. 2005 Jul 1;62(3):846-53. doi: 10.1016/j.ijrobp.2005.02.048.

  PMID: 15936569 BACKGROUND

• Chahal M, Xu Y, Lesniak D, Graham K, Famulski K, Christensen JG, Aghi M, Jacques A, Murray D, Sabri S, Abdulkarim B. MGMT modulates glioblastoma angiogenesis and response to the tyrosine kinase inhibitor sunitinib. Neuro Oncol. 2010 Aug;12(8):822-33. doi: 10.1093/neuonc/noq017. Epub 2010 Feb 23.

  PMID: 20179017 BACKGROUND

• Bischof M, Abdollahi A, Gong P, Stoffregen C, Lipson KE, Debus JU, Weber KJ, Huber PE. Triple combination of irradiation, chemotherapy (pemetrexed), and VEGFR inhibition (SU5416) in human endothelial and tumor cells. Int J Radiat Oncol Biol Phys. 2004 Nov 15;60(4):1220-32. doi: 10.1016/j.ijrobp.2004.07.689.

  PMID: 15519795 BACKGROUND

MeSH Terms

Conditions

Glioblastoma

Interventions

Sunitinib; Temozolomide; Radiotherapy

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Therapeutics

Central Study Contacts

Bassam Abdulkarim, MD PhD FRCPC

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PhD, MD

Study Record Dates

• First Submitted: January 14, 2016
• First Posted: October 10, 2016
• Study Start: August 1, 2012
• Primary Completion: December 1, 2016
• Study Completion: June 1, 2017
• Last Updated: October 10, 2016

Record last verified: 2016-10

Locations

CA (2)