| Eligibility |
Inclusion Criteria:
- Histologically confirmed newly diagnosed grade IV glioma (gliosarcoma allowed)
- The subject must have recovered from the effects of surgery, postoperative infection,
and other complications before enrollment. Post-operative unenhanced and
contrast-enhanced MRI scan should be done within 72 hours after surgery. If it is not
obtained within 72 hours post-resection, then an MRI obtained at least 2 weeks (or
longer) after surgery is required
- Karnofsky performance status >= 70%
- Absolute neutrophil count >= 1,500/mm^3 (=< 21 days prior to registration)
- Platelets >= 100,000/mm^3 (=< 21 days prior to registration)
- Hemoglobin (Hgb) >= 9.0 g/dL (Note: The use of transfusion or other intervention to
achieve Hgb >= 9.0 g/dL is acceptable.) (=< 21 days prior to registration)
- Calculated creatinine clearance >= 30 mL/min by Cockcroft-Gault formula (=< 21 days
prior to registration)
- Total bilirubin =< 1.5 times upper limit of normal (ULN) (=< 21 days prior to
registration)
- Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT])
=< 1.5 times upper limit of normal (ULN) (=< 21 days prior to registration)
- Female subjects of childbearing potential (i.e., those who are not postmenopausal for
at least 1 year or surgically sterile by bilateral tubal ligation, bilateral
oophorectomy or hysterectomy) and their male partners should practice at least one of
the methods of birth control listed below during study entry, for the entire duration
of the study and for at least 6 months after treatment with temozolomide and
chloroquine:
* A vasectomized male subject or a vasectomized partner of a female subject; hormonal
contraceptives (oral, parenteral, or transdermal) for at least 3 months prior to study
drug administration; intrauterine device (females); double-barrier method (condoms,
contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream)
- Female subjects of child-bearing potential must have a negative pregnancy test (urine
or serum) within 3 days of registration
- Must voluntarily sign and date informed consent form for study participation, approved
by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to
the initiation of any screening or study-specific procedures
Exclusion Criteria:
- Gliomatosis cerebri (a diffuse glioma [usually astrocytic] growth pattern consisting
of exceptionally extensive infiltration of a large region of the central nervous
system, with involvement of at least 3 cerebral lobes, usually with bilateral
involvement of the cerebral hemispheres and/or deep grey matter, and frequent
extension to the brain stem, cerebellum, and even the spinal cord.)
- Recurrent glioblastoma (GBM)
- Metastatic GBM
- Infratentorial tumor
- Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note
that prior chemotherapy for a different cancer is allowable, except prior
temozolomide. Implanted carmustine (BCNU) wafer is allowed
- Prior radiotherapy to the head or neck (except for T1 glottic cancer or
nonmelanomatous skin cancer), resulting in overlap of radiation fields
- Any prior therapy for glioblastoma besides surgery (intra-operative techniques to
guide resection and experimental imaging techniques are allowed). BCNU wafer is
allowed
- Prior invasive malignancy (except for non-melanomatous skin cancer; carcinoma in situ
(CIS) of the breast, CIS oral cavity, or CIS cervix, T1 glottic cancer) unless disease
free for >= 5 years
- Prior, concomitant, or planned concomitant treatment with bevacizumab, carmustine
implant (Gliadel) wafers or other intratumoral or intracavitary anti-neoplastic
therapy, or other experimental therapeutics intended to treat the tumor; the
exceptions are diagnostic and operative guides to improve extent of resection or
imaging studies, quality of life, biomarker, or epidemiological studies
- History of hypersensitivity to temozolomide or excipients
- Known glucose-6-phosphate dehydrogenase (G6PD) deficiency
- Lactating or pregnant female
- Severe, active, co-morbidity defined as follows:
* Moderate or severe hepatic impairment (Child-Pugh category B or higher [score of 7
or higher ]); unstable angina and/or congestive heart failure within the last 6
months; transmural myocardial infarction within the last 6 months; evidence of recent
myocardial infarction or ischemia by the findings of S-T elevations of >= 2 mm using
the analysis of an electrocardiogram (EKG) performed within 14 days prior to
enrollment; New York Heart Association grade II or greater congestive heart failure
requiring hospitalization within 12 months prior to enrollment
- History of stroke, cerebral vascular accident (CVA), or transient ischemic attack
within 6 months (except if intra- or post-operative); serious and inadequately
controlled cardiac arrhythmia; acute bacterial or fungal infection requiring
intravenous antibiotics at the time of enrollment; chronic obstructive pulmonary
disease exacerbation or other respiratory illness requiring hospitalization or
precluding study therapy at the time of enrollment; uncontrolled human
immunodeficiency virus (HIV) with CD4 count < 200; note, however, that HIV testing is
not required for entry into this protocol
- Any other major medical illnesses or psychiatric impairments that in the
investigator's opinion will prevent administration or completion of protocol therapy
- Subjects treated on any other therapeutic clinical protocols within 30 days prior to
study entry or during participation in the study, except intra-operative therapy to
guide resection or experimental imaging without therapeutic intent
- Inability to undergo contrast-enhanced MRI scans
- Presence of implanted pacemaker, programmable shunts, defibrillator, deep brain
stimulator, or other implanted electronic devices in the brain
- Documented clinically significant arrhythmia or severe ischemic heart disease
- Patients with underlying ocular disorders, including but not limited to: maculopathy,
macular degeneration, and retinopathy
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