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Phase I Dose Finding Study of Sorafenib in Combination With Radiation Therapy and Temozolomide as a First Line Treatment of Patients With High Grade Glioma


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Glioblastoma, Gliosarcoma, Anaplastic Astrocytoma, Anaplastic Oligoastrocytoma, Anaplastic Oligodendroglioma

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Trial Information

Phase I Dose Finding Study of Sorafenib in Combination With Radiation Therapy and Temozolomide as a First Line Treatment of Patients With High Grade Glioma


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.


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.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Description:

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

Outcome Time Frame:

35 weeks

Safety Issue:

Yes

Principal Investigator

Pierre-Yves Dietrich, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Department of oncology, Geneva University hospital

Authority:

Switzerland: Swissmedic

Study ID:

08-122

NCT ID:

NCT00884416

Start Date:

March 2009

Completion Date:

December 2011

Related Keywords:

  • Glioblastoma
  • Gliosarcoma
  • Anaplastic Astrocytoma
  • Anaplastic Oligoastrocytoma
  • Anaplastic Oligodendroglioma
  • 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
  • Astrocytoma
  • Glioblastoma
  • Glioma
  • Oligodendroglioma
  • Gliosarcoma

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