- INCLUSION CRITERIA

3.1.1 Tumor

Patients with sporadic (non NF-1 associated), histologically diagnosed pilocytic
astrocytoma who have pre- treatment tumor tissue available for BRAF analysis are eligible.
NF-1 patients with radiographic evidence of low grade glioma, with or without histological
diagnosis are also eligible. Patients will be assigned to one of 4 strata following
enrollment.

- Stratum 1: Patients with progressive, recurrent or refractory pilocytic astrocytoma
with pre-trial tumor material available and with a BRAF aberration i.e. BRAF (V600E)
mutation and/or BRAF KIAA1549 fusion as determined by IHC and FISH, respectively.

- Stratum 2: Patients with progressive, recurrent or refractory pilocytic astrocytoma
with pre-trial tumor material available and without a BRAF aberration i.e. BRAF
(V600E) mutation and/or BRAF KIAA1549 fusion as determined by IHC and FISH,
respectively.

- Stratum 3: Patients with Neuro-fibromatosis 1 (NF-1) associated progressive,
recurrent or refractory low grade glioma (WHO Grade I & II), with or without tissue

- Stratum 4: Non-NF-1 recurrent or refractory pilocytic astrocytoma patients who cannot
be classified into Stratum 1 or 2 due to inadequate tissue quality or assay failure.

3.1.2 Patients must have bi-dimensionally measureable disease defined as at least one
lesion that can be accurately measured in at least two planes in order to be eligible for
this study.

3.1.3 Prior Therapy

Patients must have received prior therapy other than surgery and must have fully recovered
from the acute toxic effects of all prior chemotherapy, immunotherapy, biologic therapy or
radiotherapy prior to entering this study.

3.1.3.1 Myelosuppressive chemotherapy: Patients must have received their last dose of
known myelosuppressive anticancer chemotherapy at least three weeks prior to study
registration or at least six weeks if nitrosourea.

3.1.3.2 Biologic agent: Patient must have received their last dose of the biologic agent
(Bullet) 7 days prior to study registration.

--For biologic agents that have a prolonged half-life, at least three half-lives must have
elapsed prior to registration

3.1.3.3 Monoclonal antibody treatment: At least three half-lives must have elapsed prior
to registration.

Note: A list of the half-lives of commonly used monoclonal antibodies is available on the
PBTC webpage under Generic Forms and Templates.

3.1.3.4 Radiation: Patients must have:

- Had their last fraction of local irradiation to primary tumor (Bullet)12 months prior
to registration; investigators are reminded to review potentially eligible cases to
avoid confusion with pseudo-progression.

- Had their last fraction of craniospinal irradiation (> 24Gy) > 3 months prior to
registration

3.1.3.5 Corticosteroids: Patients who are receiving dexamethasone must be on a stable or
decreasing dose for at least 1 week prior to registration.

3.1.3.6 Growth factors: Patients must be off all colony-forming growth factor(s) for at
least 1 week prior to registration (filgrastim, sargramostim, erythropoietin) and at least
2 weeks for long-acting formulations.

3.1.4 Age

Patient must be greater than or equal to 3 but less than or equal to 21 years of age at
registration.

3.1.5 BSA

Patients must have BSA greater than or equal to 0.55 m(2).

3.1.6 Neurological Status

Patients with neurological deficits should have deficits that are stable for a minimum of
1 week prior to registration.

3.1.6.1 Patients must be able to swallow capsules

3.1.7 Performance Status

Karnofsky Performance Scale (KPS for > 16 yrs. of age) or Lansky Performance Score (LPS
for less than or equal to 16 years of age) greater than or equal to 60 assessed within two
weeks prior to registration.

3.1.8 Organ Function

Patients must have normal organ and marrow function documented within 14 days of
registration and within 7 days of the start of treatment as noted below:

- Absolute neutrophil count greater than or equal to 1,000/ L (unsupported)

- Platelets greater than or equal to 100,000/ L (unsupported)

- Hemoglobin greater than or equal to 8 g/dL (may be supported)

- Total bilirubin < 1.5 times upper limit of normal for age

- AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X institutional upper limit of normal
for age

- Creatinine clearance or radioisotope GFR greater than or equal to 70 ml/min/1.73m(2)
or a serum creatinine based on age as follows:

- Age(years) less than or equal to 5, Maximum Serum Creatinine (mg/dL) 0.8

- Age(years) > 5 but less than or equal to 10, Maximum Serum Creatinine (mg/dL) 1

- Age(years) > 10 but less than or equal to 15, Maximum Serum Creatinine (mg/dL)
1.2

- Age(years) > 15, Maximum Serum Creatinine (mg/dL) 1.5

- Sodium, Potassium within the institutional limits of normal

- Calcium and Magnesium above the institutional lower limit of normal

- Albumin greater than or equal to 3g/dL

3.1.9 Cardiac Function

Adequate cardiac function defined as:

- LVEF greater than or equal to 50%

- QTc interval less than or equal to 450 msecs

3.1.10 Hypertension

- Patients, 3-17 years of age must have a blood pressure that is less than or equal to
95th percentile for age, height and gender at the time of registration.

--The normal blood pressure by height, age and gender tables can be accessed in the
Generic Forms section of the PBTC members webpage.

- Patients who are greater than or equal to 18 years of age must have a blood pressure
that is < 140/90 mm of Hg at the time of registration.

Note: If a BP reading prior to registration is above the 95th percentile for age, height
and gender it must be rechecked and documented to be less than or equal to the 95th
percentile for age, height and gender prior to patient registration.

3.1.11 Pregnancy Status

Female patients of childbearing potential must not be pregnant or breast-feeding. Female
patients of childbearing potential must have a negative serum or urine pregnancy test.

3.1.12 Pregnancy Prevention

The effects of AZD6244 on the developing human fetus are unknown. For this reason, women
of child-bearing potential and men must agree to use adequate contraception (hormonal or
barrier method of birth control; abstinence) prior to study entry and for the duration of
study participation, and for four weeks after dosing with AZD6244 ceases. Women of
child-bearing potential must have a negative pregnancy test prior to entry. Should a woman
become pregnant or suspect she is pregnant while she or her partner is participating in
this study, she should inform her treating physician immediately. Please note that the
AZD6244 manufacturer recommends that adequate contraception for male patients should be
used for 16 weeks post-last dose due to sperm life cycle.

3.1.13 Informed Consent

Ability to understand and the willingness to sign a written informed consent document
according to institutional guidelines.

EXCLUSION CRITERIA

3.2.1 Patients with any clinically significant unrelated systemic illness (serious
infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), likely
interfere with the study procedures or results.

3.2.2 Patients who are receiving any other anticancer or investigational agents.

3.2.3 Patients with uncontrolled seizures

3.2.4 Previous MEK inhibitor use such as PD-0325901; CI1040; AS73026; GDC 0973; ARRY43182;
GSK110212.

3.2.5 Prior treatment with a BRAF inhibitor such as Venurafenib or Debrafenib

3.2.6 Patients with other factors that increase the risk of QT prolongation or arrhythmic
events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome)
that meets New York Heart Association (NYHA) class II or above (APPENDIX B)

3.2.7 Required use of a concomitant medication that can prolong the QT interval. See
APPENDIX C for a table of medications with the potential to prolong the QTc interval.

3.2.8 History of allergic reactions attributed to compounds of similar chemical or
biologic composition to AZD6244.

Minimum Eligible Age: 3 Years

Maximum Eligible Age: 21 Years

Eligible Gender: Both