Sorafenib in Newly Diagnosed High Grade Glioma

NCT00884416 | Completed Phase 1 DMC

• 3 other identifiers: 08-1222009DR102913031
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I study to evaluate the safety and tolerability of Sorafenib in combination with Temodar and radiation therapy in patients with newly diagnosed high grade glioma (glioblastoma, gliosarcoma, anaplastic astrocytoma and anaplastic oligodendroglioma or oligoastrocytoma). The mechanism of action of sorafenib, an oral multikinase inhibitor, makes it an interesting drug to investigate in the treatment of patients with high grade glioma as this agent has anti-angiogenic activity and inhibits other pathways such as Ras, Platelet-derived growth factor (PDGF) and fms-like tyrosine kinase receptor-3 (Flt-3), which are potential targets against gliomas.

Conditions

Glioblastoma; Gliosarcoma; Anaplastic Astrocytoma; Anaplastic Oligoastrocytoma; Anaplastic Oligodendroglioma

Keywords

high grade glioma; glioblastoma; gliosarcoma; anaplastic astrocytoma; anaplastic oligoastrocytoma; anaplastic oligodendroglioma; phase I; first line treatment; sorafenib; temozolomide; radiation therapy; safety; tolerability; protein kinase inhibitors

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of sorafenib in combination with radiation and temozolomide chemotherapy

  Safety and tolerability of sorafenib in combination with radiation and temozolomide chemotherapy in patients with newly diagnosed high grade glioma

  35 weeks

Secondary Outcomes (6)

• Maximum Observed Plasma Concentration (Cmax) and Area under the curve (AUC) of sorafenib and temozolomide

  0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post dose

• Response rate

  35 weeks

• Time to treatment failure

  20 months

• 6 month progression-free survival

  6 months

• Event free survival

  20 months

Study Arms (1)

Sorafenib dose titration

EXPERIMENTAL

Drug: Sorafenib dose escalation

Interventions

Sorafenib dose escalation DRUG

Sorafenib dose escalation scheme: 3 first patients: 200 mg/d, if dose limiting toxicities (DLT) not reached: 3 patients at 200 mg BID, if no DLT reached: 3 patients at 400 mg bid

Sorafenib dose titration

Eligibility Criteria

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

You may qualify if:

• Histological documentation of newly diagnosed malignant glioma
• ECOG performance status of 0 or 1
• Age ≥18
• Life expectancy of at least 12 weeks
• Hemoglobin ≥ 9.0 g/dl
• Granulocyte count ≥1.5 X 10\^9/L
• Platelet count ≥100 X 10\^9/L
• SGOT ≤ 2.5X upper limit of normal (ULN)
• SGPT ≤ 2.5X upper limit of normal (ULN)
• Alkaline phosphatase ≤4x ULN
• Serum creatinine ≤1.5X ULN
• Bilirubin ≤1.5X ULN
• Spontaneous PT-INR/PTT \< 1.5x upper limit of normal (patients on therapeutic anticoagulation will be allowed to participate.
• Patients must be on a stable or decreasing dose of corticosteroids for at least 2 weeks
• Patient for whom a first line treatment with temozolomide and radiotherapy is adequate

You may not qualify if:

• Prior treatment for high grade glioma
• Previous exposure to Ras pathway inhibitors
• Other concurrent active malignancy (with the exception of cervical carcinoma in situ or non melanoma carcinoma of the skin, superficial bladder tumor \[Ta, Tis \& T1\] or any cancer curatively treated \> 3 years prior to study entry).
• Serious medical or psychiatric illness that would, in the opinion of the investigator, interfere with the prescribed treatment, including but not limited to: Congestive heart failure \> NYHA class 2, active CAD, cardiac arrythmias requiring anti-arrythmic therapy or uncontrolled hypertension within the last 12 months
• Any condition limiting the patient's judgment capacity
• History of HIV infection, chronic hepatitis C or B as well as clinically active infections (\> grade 2 NCI-CTC version 3.0)
• History of organ allograft
• Renal dialysis
• Evidence or history of bleeding diathesis
• Major surgery within 4 weeks of start of study treatment, except for neurosurgical resection
• Autologous bone marrow transplant or stem cell rescue within 4 months of study
• Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of study results.
• Medical condition that prevents the patient from swallowing pills
• Use of biologic response modifiers, such as G-CSF within 3 week of study entry.
• Pregnant or breast-feeding women.

Sponsors & Collaborators

• University Hospital, Geneva: lead
• Bayer: collaborator

Study Sites (1)

Geneva University Hospital (Hopitaux Universitaires de Geneve), Department of Oncology

Geneva, Canton of Geneva, 1211, Switzerland

Location

Related Publications (1)

• Hottinger AF, Ben Aissa A, Espeli V, Squiban D, Dunkel N, Vargas MI, Hundsberger T, Mach N, Schaller K, Weber DC, Bodmer A, Dietrich PY. Phase I study of sorafenib combined with radiation therapy and temozolomide as first-line treatment of high-grade glioma. Br J Cancer. 2014 May 27;110(11):2655-61. doi: 10.1038/bjc.2014.209. Epub 2014 May 1.

  PMID: 24786603 RESULT

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Astrocytoma; Oligodendroglioma; Glioma

Condition Hierarchy (Ancestors)

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

Study Officials

• Pierre-Yves Dietrich, MD

  Department of oncology, Geneva University hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 17, 2009
• First Posted: April 20, 2009
• Study Start: March 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: March 1, 2012
• Last Updated: November 4, 2014

Record last verified: 2014-10

Locations

CH (1)