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An Exploratory Pharmacodynamic Study of XL765 and XL147 Administered as Single Agents to Subjects With Recurrent Glioblastoma Who Are Candidates for Surgical Resection

Phase 1
18 Years
Not Enrolling
Glioblastoma, Astrocytoma, Grade IV

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Trial Information

An Exploratory Pharmacodynamic Study of XL765 and XL147 Administered as Single Agents to Subjects With Recurrent Glioblastoma Who Are Candidates for Surgical Resection

Inclusion Criteria:

1. The subject has histologically confirmed diagnosis of primary GB for which the
subject has received prior treatment, including radiation and/or chemotherapy, and
will be undergoing a second surgical resection.

2. The subject has available archival tumor tissue from the time of initial diagnosis of
GB that is designated for central laboratory analysis.

3. The subject is ≥ 18 years old.

4. The subject has a Karnofsky performance status (KPS) ≥ 60%.

5. The subject has adequate organ and marrow function.

6. The subject has adequate fasting plasma glucose levels and glycosylated hemoglobin

7. The subject is capable of understanding and complying with the protocol requirements
and has signed the informed consent document.

8. Sexually active subjects (men and women) must agree to use medically-accepted barrier
methods of contraception during the course of the study and for 3 months after the
last dose of study drug, even if oral contraceptives are also used. All subjects of
reproductive potential must agree to use both a barrier method and a second method of
birth control.

9. Women of childbearing potential must have a negative pregnancy test at screening.

Exclusion Criteria:

1. The subject has confirmed secondary GB (ie, had a pathology-confirmed lower-grade
glioma that subsequently recurred as a higher grade glioma).

2. The subject's tumor has a predominance of WHO Grade IV oligoastrocytoma.

3. The subject has received radiation therapy for GB within 12 weeks (≤ 84 days) before
their first dose of study drug treatment.

4. The subject has received specific types of anticancer therapy (should be discussed
with the treating physician)

5. The subject has not recovered to National Cancer Institute (NCI) Common Terminology
Criteria for Adverse Events (CTCAE) version 4.0 Grade ≤ 1 from AEs due to surgery,
radiation, antineoplastic agents, investigational drugs, or other medications that
were administered before screening (except Grade 2 alopecia and Grade 2

6. The subject is receiving > 1 mg/day warfarin (or equivalent of other coumarin
derivatives) and is unable to switch to low molecular weight heparin within 14 days
before the first dose of study drug.

7. The subject is receiving enzyme-inducing anti-epileptic agents (EIAED; eg,
carbamazepine, phenytoin, phenobarbital, or primidone) or valproic acid and is unable
to convert to EIAED anti-seizure agents within 14 days before the first dose of study

8. The subject has uncontrolled intercurrent illness including, but not limited to:

- Ongoing or active infection

- Hypertension (consistent blood pressure readings of > 140 mmHg systolic or > 100
mmHg diastolic) despite optimal treatment

- Significant cardiac arrhythmias, or a recent history of serious disease, such as
either symptomatic congestive heart failure or unstable angina pectoris within 3
months, or the following events within 6 months: myocardial infarction, stroke,
or transient ischemic attack.

- Inherited or acquired bleeding diathesis

9. The subject has a baseline corrected QT interval (QTc) > 460 ms.

10. The subject is unable to undergo repeated magnetic resonance imaging (MRI) scans for
any reason (eg, cardiac pacemaker or ferromagnetic metal implants).

11. The subject is known to be positive for the human immunodeficiency virus (HIV). Note:
HIV testing is not required for eligibility.

12. The subject has impairment of gastrointestinal function or gastrointestinal disease
that may significantly alter the absorption of study treatment (eg, ulcerative
disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small
bowel resection).

13. The subject is pregnant or breastfeeding.

14. The subject has a previously identified allergy or hypersensitivity to components of
the study treatment formulation.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To explore the biological effect of XL765 and XL147 measured by modulation of PI3K/ mTOR pathway readouts in GB tumor tissue

Outcome Time Frame:

Assessed between 10 and 28 days after initiation of study drug

Safety Issue:


Principal Investigator

Clinical Sciences & Operations

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

January 2011

Completion Date:

June 2012

Related Keywords:

  • Glioblastoma
  • Astrocytoma, Grade IV
  • Astrocytoma
  • Glioblastoma



Investigational Site Number 840001 Vallejo, California  94589
Investigational Site Number 840003 San Diego, California  92123
Investigational Site Number 840004 Boston, Massachusetts  02115
Investigational Site Number 840002 New York, New York  10021