Sorafenib in Newly Diagnosed High Grade Glioma

University Hospitals (UH)

Status and phase

Completed

Phase 1

Conditions

Glioblastoma

Anaplastic Oligoastrocytoma

Gliosarcoma

Anaplastic Oligodendroglioma

Anaplastic Astrocytoma

Treatments

Drug: Sorafenib dose escalation

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00884416

08-122

13031

2009DR1029

Details and patient eligibility

About

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.

Full description

Up to 18 patients will be included in this phase I study. The primary goal of this study will be to establish the maximum tolerated dose of sorafenib when used in combination with temozolomide and radiation therapy. Secondary goals of this study include: response rate, time to treatment failure, 6 month progression-free survival, event free survival and overall survival. A correlative study will investigate the pharmacokinetics of sorafenib used in combination with radiation therapy and temozolomide.

Enrollment

17 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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
Prophylactic anti-emetic, pentamidine inhalation / co-trimoxazole and anticonvulsants are allowed
All patients must sign written informed consent.

Exclusion criteria

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.
Refusal to use effective contraception. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and for at least 3 months after administration of study medication.
Known or suspected allergy to the investigational agent or any agent given in association with this trial.