Overview

Phase I Portion of Phase I/II Sorafenib With Radiation and Temozolomide in Newly Diagnosed Glioblastoma or Gliosarcoma

Status:
Terminated
Trial end date:
2012-12-01
Target enrollment:
0
Participant gender:
All
Summary
The goal of this clinical research study is to find the highest tolerable dose of sorafenib that can be given in combination with temozolomide. The safety of this combination will also be studied.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
M.D. Anderson Cancer Center
Collaborator:
Bayer
Treatments:
Dacarbazine
Niacinamide
Sorafenib
Temozolomide
Criteria
Inclusion Criteria:

1. Histopathologically proven diagnosis of glioblastoma. Since gliosarcoma is a variant
of glioblastoma, gliosarcoma is also an eligible diagnosis.

2. Patients must have at least 1 block of tumor tissue available for submission to the
central pathologist for analysis of gene expression status by QRT-PCR; there must be
at least 1 cm^2 of tumor from the block when cut on a slide: fresh frozen tumor tissue
acquisition is also encouraged, but not required. Unstained slide submission without a
block submission is not acceptable for study entry.

3. Diagnosis must be established by open biopsy or tumor resection. Patients who have
only had a stereotactic biopsy are not eligible..

4. The tumor must have a supratentorial component.

5. Patients must have recovered from the effects of surgery, postoperative infection, and
other complications before study registration.

6. All patients must sign an informed consent indicating that they are aware of the
investigational nature of this study.

7. A diagnostic contrast-enhanced MRI or CT scan (if MRI is contraindicated) of the brain
must be performed postoperatively in the period between surgery and initiation of
radiation therapy.

8. Therapy must begin
9. History/physical examination within 14 days prior to study registration.

10. Neurologic examination within 14 days prior to study registration.

11. Documentation of steroid doses within 14 days prior to study registration and stable
or decreasing steroid dose within 5 days prior to registration.

12. Karnofsky performance status of >/= 60.

13. Age >/= 18 years.

14. Patients with well-controlled hypertension are eligible (systolic blood pressure of

15. Complete blood count (CBC)/differential obtained within 14 days prior to study
registration, with adequate bone marrow function as defined below: Absolute neutrophil
count (ANC) >/= 1500 cells/mm^3; Platelets >/= 100,000 cells/mm^3;Hemoglobin >/= 10
g/dl.

16. Adequate renal function, as defined below: Serum creatinine days prior to study registration

17. Adequate hepatic function, as defined below: Bilirubin prior to study registration; ALT days prior to study registration; AST registration

18. Fasting cholesterol < 300 mg/dL (9.0 mmol/L) and fasting triglycerides < 2.5 times ULN

19. International normalized ratio (INR) < 1.5 or a PT/PTT within normal limits for
patients not on anti-coagulation treatment

20. Patients receiving anti-coagulation treatment with an agent such as warfarin or low
molecular weight heparin may be allowed to participate with the following criteria:
For patients on prophylactic anticoagulation therapy (low-dose warfarin): INR level <
1.5; Patients on prophylactic dose or full dose low molecular weight heparins are
eligible provided that the patient has no active bleeding or pathological condition
that carries a high risk of bleeding;

21. (20. continued) Patients on full-dose anticoagulants (e.g., warfarin) are eligible
provided that both of the following criteria are met: (a) Patient has an in-range INR
(usually between 2-3) on a stable dose or oral anticoagulant or on a stable dose of
low molecular weight heparin. (b) Patient has no active bleeding or pathological
condition that carries a high risk of bleeding.

22. If the patient's mental status precludes his/her giving informed consent, written
informed consent may be given by the responsible family member.

23. For females of child-bearing potential, negative serum pregnancy test within 72 hours
prior to starting temozolomide

24. Women of childbearing potential and men must agree to use adequate contraception
(barrier method of birth control) prior to study entry and for the duration of study
participation. Men should use adequate birth control for at least six months after the
last administration of sorafenib or temozolomide.

Exclusion Criteria:

1. Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease
free for >/= 3 years.

2. Recurrent or multifocal malignant gliomas

3. Metastases detected below the tentorium or beyond the cranial vault.

4. Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note
that prior chemotherapy for a different cancer is allowable.

5. Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are
not permitted.

6. Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in
overlap of radiation fields.

7. Severe, active co-morbidity, defined as follows: Cardiac disease - Congestive heart
failure > class II New York Heart Association (NYHA). Patients must not have unstable
angina (anginal symptoms at rest) or new onset angina (began within the last 3 months)
or myocardial infarction within the past 6 months; Cardiac ventricular arrhythmias
requiring anti-arrhythmic therapy; Acute bacterial or fungal infection requiring
intravenous antibiotics at the time of registration; Chronic Hepatitis B or C
infection;

8. (7. continued) Chronic Obstructive Pulmonary Disease exacerbation or other respiratory
illness requiring hospitalization or precluding study therapy at the time of
registration; Hepatic insufficiency resulting in clinical jaundice and/or coagulation
defects;

9. (7. continued) Known history or symptoms and laboratory results consistent with
Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition (note,
however, that HIV testing is not required for entry into this protocol. The need to
exclude patients with AIDS from this protocol is necessary because the treatments
involved in this protocol may be significantly immunosuppressive); Major medical
illnesses or psychiatric impairments that in the investigator's opinion will prevent
administration or completion of protocol therapy;

10. (7. continued) Active connective tissue disorders, such as lupus or scleroderma, that
in the opinion of the treating physician may put the patient at high risk for
radiation toxicity; Arterial thrombotic or embolic events such as a cerebrovascular
accident including transient ischemic attacks within the past 6 months; Pulmonary
hemorrhage/bleeding event > Common Toxicity Criteria for Adverse Effects (CTCAE) Grade
2 within 4 weeks of first dose of study drug;

11. (7. continued) Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of
first dose of study drug; Serious non-healing wound, ulcer, or bone fracture; Evidence
or history of bleeding diathesis or coagulopathy

12. Uncontrolled hypertension defined as systolic blood pressure > 140 mmHg or diastolic
pressure > 90 mmHg, despite optimal medical management.

13. Major surgery, open biopsy or significant traumatic injury within 4 weeks of first
study drug.

14. Use of St. John's Wort or rifampin (rifampicin).

15. Pregnancy or women of childbearing potential and men who are sexually active and not
willing/able to use medically acceptable forms of contraception; this exclusion is
necessary because the treatment involved in this study may be significantly
teratogenic.

16. No tissue provided for histopathologic review and QRT-PCR analysis.