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|NCT01110876 : Phase I / II Vorinostat, Erlotinib and Temozolomide for Recurrent Glioblastoma Multiforme (GBM)|
|Phase||Phase 1/Phase 2|
|Ages||Min: 18 Years Max: N/A|
1. Patients with histologically proven glioblastoma multiforme, gliosarcoma or
anaplastic glioma will be eligible for the Phase I component. Anaplastic gliomas
include anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic
oligoastrocytoma (AOA), or malignant glioma NOS (not otherwise specified). Patients
will be eligible if the original histology was low-grade glioma and a subsequent
histological diagnosis of a malignant glioma is made. Only patients with
histologically proven supratentorial glioblastoma multiforme or gliosarcoma will be
eligible for the Phase II component.
2. Patients must have shown unequivocal evidence for tumor recurrence or progression by
MRI scan and should have failed radiation therapy. Patients should have completed
radiation therapy at least 3 months prior to entry into the study. The scan done
prior to study entry documenting progression will be reviewed by the treating
physician to document changes in tumor dimension to confirm recurrence.
3. (2. continued) Patients with prior therapy that included interstitial brachytherapy
or stereotactic radiosurgery must have reasonable confirmation of true progressive
disease rather than radiation necrosis as determined by the treating physician and
neuro-radiologist; for example, through MRI, MR spectroscopy, or PET scan of the
4. For the Phase I component, any number of prior relapses is allowed, provided the
patient fulfills all other eligibility criteria particularly that of the functional
status. For the phase II component, patients may have had up to 2 prior relapses
5. All patients must sign an informed consent indicating their awareness of the
investigational nature of this study in keeping with the policies of this hospital.
6. The baseline on-study MRI should be performed within 14 days (+/- 3 days) prior to
registration and on a steroid dosage that has been stable or decreasing for at least
5 days. If the steroid dose is increased between the date of imaging and the
initiation of therapy (or at that time), a new baseline MRI is required. The same
type of scan, i.e., MRI, must be used throughout the period of protocol treatment for
7. Patients having undergone recent resection of recurrent or progressive tumor will be
eligible as long as all of the following conditions apply: a) They have recovered
from the effects of surgery. b) Evaluable or measurable disease following resection
of recurrent tumor is not mandated for eligibility into the study. c) To best assess
the extent of residual measurable disease post-operatively, a MRI should be done no
later than 96 hours in the immediate post-operative period or 4-6 weeks
8. Patients must be 18 years old or older.
9. Patients must have a Karnofsky performance status (KPS) equal or greater than 60
10. Patients must have recovered from the toxic effects of prior therapy to grade 1 non
hematological or = grade 2 hematological toxicity (except deep vein thrombosis): 4
weeks from prior cytotoxic therapy or bevacizumab and/or at least two weeks from
vincristine, 6 weeks from nitrosoureas, 3 weeks from procarbazine administration, and
1 week for non-cytotoxic agents, e.g., interferon, tamoxifen, cis-retinoic acid, etc.
(radiosensitizer does not count).
11. (10. continued) Patients who receive anticancer agents for non-therapeutic purposes
unrelated to this study (such as presurgically for obtaining pharmacology data for
the agent) will be eligible to enter the study provided they have recovered from the
toxic effects of the agent if any. Any questions related to the definition of
non-cytotoxic agents should be directed to the Study Chair.
12. Patients must have adequate bone marrow function (ANC>/= 1,500/mm^3 and platelet
count of >/= 100,000/mm^3), adequate liver function (SGPT = 3 times normal and
alkaline phosphatase = 2 times normal, bilirubin = 1.5 mg/dl), adequate renal
function (BUN and creatinine = 1.5 times institutional normal) prior to
13. Women of childbearing potential on treatment must not be pregnant, must not be
breast-feeding and must practice adequate contraception. Male patients on treatment
with vorinostat must agree to use an adequate method of contraception for the
duration of the study, and for 30 days after the last dose of study medication.
1. Patients with a history of any other cancer (except non-melanoma skin cancer or
carcinoma in-situ of the cervix or bladder), unless in complete remission and off of
all therapy for that disease for a minimum of 3 years are ineligible.
2. Patients must not have: a) active infection b) disease that will obscure toxicity or
dangerously alter drug metabolism, especially liver disease including cirrhosis or
hepatic dysfunction c) serious intercurrent medical illness
3. Patients who are currently on active treatment for AIDS or hepatitis will be excluded
due to the potential for adverse interaction with ongoing treatment agents and for
4. Patients receiving valproic acid (VPA), an anticonvulsant drug with HDAC inhibitor
properties, will be excluded, unless they are switched to an alternative agent prior
to treatment initiation. A 5 day wash out period is required.
5. Prior treatment with EGFR inhibitors or temozolomide on a standard day 1-5 dosing and
low dose daily dosing as part of chemoradiation therapy is allowed because the trial
is based on the hypothesis that the combination of agents used will be synergistic in
their effects, and that HDAC inhibition will potentially overcome resistance to EGFR
inhibitors and temozolomide. However, prior treatment with dose dense regimens of
temozolomide (7 days on/ 7 days off, 21 days/28 days or continuous low dose daily
dosing not with chemoradiation) and HDAC inhibitors other than valproic acid (such as
depsipeptide, LBH-589 or vorinostat) are not permitted.
6. Patients with a known allergy to any component of vorinostat, or a known allergy to
Temozolomide or erlotinib will be excluded.
7. Patient must be able to tolerate the procedures required in this study including
periodic blood sampling, study related assessments, and management at the treating
institution for the duration of the study. Inability to comply with protocol or study
procedures (for example, an inability to swallow tablets) will be an exclusion
8. This study was designed to include women and minorities, but was not designed to
measure differences of intervention effects. Males and females will be recruited with
no preference to gender.
9. No exclusion to this study will be based on race. The malignant glioma patient
population treated at MDACC over the past year is as follows: American Indian or
Alaskan Native - 0; Asian or Pacific Islander - <2%; Black, not of Hispanic Origin -
3%; Hispanic - 6%; White, not of Hispanic Origin - 88%; Other or Unknown - 2%;
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