Trial of Temozolomide, Bevacizumab Plus Bortezomib for Recurrent Glioblastoma Multiforme

Status:Active, not recruiting
Conditions:Brain Cancer
Therapuetic Areas:Oncology
Age Range:18 - Any
Start Date:December 2011
End Date:December 2016

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Phase I Trial of Temozolomide, Bevacizumab Plus Bortezomib for Patients With Recurrent Glioblastoma Multiforme

This is a single-center (Emory University), open-label, single arm, phase I study to assess
safety and toxicity of bortezomib in combination with bevacizumab and escalating doses of
temozolomide for patients with recurrent glioblastoma multiforme. Patients requiring
anti-epileptic medications will have to be at least 10 days off EIAEDs. Only non-EIAEDs are

Inclusion Criteria:

1. Age 18 years or more.

2. Patients must have histologically confirmed diagnosis of a recurrent/progressive WHO
grade IV malignant gliomas (glioblastoma multiforme and gliosarcoma).

3. Patients must have measurable progressive or recurrent disease by MRI within 2 weeks
of starting treatment.

4. No prior bortezomib is allowed.

5. An interval of at least 6 weeks between prior surgical resection, 4 weeks from the
end of prior radiotherapy.

6. Patients must be at least 10 days off any enzyme inducing anti-epileptic drugs
(EIAEDs) of the cytochrome P450 (CYP-450) such as phenytoin, carbamazepine,

7. Karnofsky performance status score of 60 or more.

8. Patients must have recovered from toxicity of prior therapy.

9. Hematocrit > 29%, absolute neutrophil count (ANC) > 1,500 cells/microliter, platelets
> 125,000 cells/microliter for 14 days prior to treatment initiation.

10. Serum creatinine < 1.5 mg/dl, serum glutamic-oxaloacetic transaminase (SGOT) and
bilirubin < 1.5 times upper limit of normal.

11. Prothrombin time/international normalized ratio (PT INR) < 1.4.

12. An interval of at least 3 months from the completion of most recent radiation
therapy. At least 4 weeks from a non-nitrosourea chemotherapy regimen and at least 6
weeks from a nitrosourea containing regimen.

13. For patients on corticosteroids, they must have been on a stable dose for 1 week
prior to entry if clinically recommended.

14. May have up to three biological therapies.

15. Voluntary written informed consent before performance of any study-related procedure
not part of normal medical care, with the understanding that consent may be withdrawn
by the subject at any time without prejudice to future medical care.

16. Female subject is either post-menopausal or surgically sterilized or willing to use
an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine
device, diaphragm with spermicide, condom with spermicide, or abstinence) for the
duration of the study.

17. Male subject agrees to use an acceptable method for contraception for the duration of
the study.

Exclusion Criteria:

1. Co-medication that may interfere with study results; e.g. immuno-suppressive agents
other than corticosteroids.

2. Greater than three prior recurrences.

3. Enzyme-inducing anti-epileptic drugs (EIAEDs) of the CYP-450 such as phenytoin,
carbamazepine, phenobarbital.

4. Patients receiving concurrent investigational drugs.

5. Evidence of central nervous system (CNS) hemorrhage on baseline MRI or CT scan
(except for grade 1 hemorrhage that has been stable for at least 3 months).

6. History of stroke within six months.

7. Requires therapeutic anti-coagulation.

8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection requiring IV antibiotics and psychiatric illness/social situations that
would limit compliance with study requirements, or disorders associated with
significant immunocompromised state.

9. Patient has a calculated or measured creatinine clearance of < 20 mL/minute within 14
days prior to treatment initiation.

10. Patient has greater or equal to Grade 2 peripheral neuropathy within 14 days before

11. Myocardial infarction within 6 months prior to enrollment or has New York Heart
Association (NYHA) Class III or IV heart failure (Appendix), uncontrolled angina,
severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of
acute ischemia or active conduction system abnormalities. Prior to study entry, any
ECG abnormality at screening has to be documented by the investigator as not
medically relevant.

12. Patient has hypersensitivity to bortezomib, boron, or mannitol.

13. Female subject is pregnant or breast-feeding. Confirmation that the subject is not
pregnant must be established by a negative serum beta-human chorionic gonadotropin
(beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not
required for post-menopausal or surgically sterilized women.

14. Patient has received other investigational drugs within 14 days of treatment

15. Serious medical or psychiatric illness likely to interfere with participation in this
clinical study.

16. Diagnosed or treated for another malignancy within 3 years of enrollment, with the
exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
Patients with prior malignancies must be disease free for at least 5 years.

17. Serious, non-healing wound, active ulcer, or untreated bone fracture. Bone fractures
must be healed.
We found this trial at
550 Peachtree St NE
Atlanta, Georgia 30308
(404) 686-4411
Emory University Hospital Midtown Emory University Hospital Midtown is a 511-bed community-based, acute care teaching...
Atlanta, GA
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Atlanta, GA
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