| Eligibility |
Inclusion Criteria:
1. Glioblastoma (GBM) according to 2016 World Health Organization (WHO) Classification.
2. Must have had a partial or complete surgical resection of the Grade 4 astrocytic
tumor.
3. Subjects in Arm 1 must have had no previous treatment except surgery (ie, no previous
RT, local CT, or systemic therapy). Subjects must meet certain other eligibility
requirements.
4. Subjects in Arm 2 must have completed a standard first line regimen of concurrent TMZ
and RT for newly diagnosed GBM patients, followed by a rest phase, and have not had
any other previous CT except surgery (including any other regimens of RT and local or
systemic CT). Progression and/or pseudoprogression should have been ruled out before
starting Arm 2 as per usual clinical practice, with correct laboratory results
(absolute neutrophile count =1.5 x 109/L, platelet count = 100 x 109/L,
non-haematological toxicity grade = 2) at screening. Subjects must meet certain other
eligibility requirements.
5. Subjects must be able to undergo serial MRIs (computerized tomography may not be a
substitute for magnetic resonance imaging [MRI]).
6. Male or female = 18 years old.
7. Must have a Karnofsky performance status of = 70% and the ability to swallow oral
medication.
8. Must have no other diagnosis of cancer malignancy (except surgically excised
nonmelanoma skin cancer or carcinoma in situ of the cervix, or treated early stage
prostate cancer, or a malignancy diagnosed = 5 years previously with no current
evidence of disease and no therapy within two years prior to enrolment on this study).
9. Must be capable of understanding and complying with the protocol requirements.
10. Contraception: All female patients will be considered to be of childbearing potential
unless they are postmenopausal (at least 12 months consecutive amenorrhea, in the
appropriate age group and without other known or suspected cause), or have been
sterilized surgically. Female patients of childbearing potential must agree to use two
forms of highly effective contraception methods (a primary and a secondary method)
during the study and for a period of 6 months following the last administration of the
study drug. Male patients and their female partners, who are of childbearing potential
and are not practicing total abstinence, must agree to use two forms of highly
effective contraception methods (a primary and a secondary method) during the study
and for a period of 6 months following the last administration of the study drug These
contraception methods include oral, transdermal, systemic or implant contraception
birth control, intra-uterine devices (IUD), abstinence and double barrier method such
as diaphragm with spermicidal gel or other recommended double barrier methods
screening.
11. Written informed consent form signed before any study test or procedure.
Exclusion Criteria:
1. Subject has received prior systemic CT or RT (Arm 1) or prior systemic CT other than
TMZ (Arm 2), biologic agents, or any other type of investigational agent for the
treatment of brain tumors.
2. Subjects who have progressed on TMZ are not eligible (pseudoprogression ruled out as
per usual clinical practice).
3. Subject has evidence of acute intracranial or intratumoral hemorrhage > Grade 1 by
MRI. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin
may enter the study.
4. Subject has serious intercurrent illness such as: hypertension despite optimal
treatment, or significant cardiac arrhythmias; or a recent history of serious disease
such as symptomatic congestive heart failure, or abdominal fistula or gastrointestinal
(GI) perforation within 6 months, prior to starting study treatment.
5. Subject has had major surgery within 28 days prior to starting study treatment (except
cancer resection surgery in arm 1), or had non water-tight dural closure during
previous surgery, or has unhealed wounds from previous surgery.
6. Subject has inherited bleeding diathesis or coagulopathy with the risk of bleeding.
7. Subject is pregnant or breastfeeding.
8. Subject is known to be positive for the human immunodeficiency virus (HIV) (a test for
HIV at screening is not required).
9. Subject has a previously-identified allergy or hypersensitivity to components of
either the LAM561 or TMZ formulations.
10. Subject is unable or unwilling to abide by the study protocol or cooperate fully with
the investigator or designee.
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