Inclusion Criteria

- ELIGIBILITY CRITERIA FOR INITIAL ENROLLMENT:

- Patients with histologically confirmed advanced NSCLC, SCLC and thymic malignancies
for whom surgical resection or multimodality therapy with curative intent is not
feasible. For patients with Stage III NSCLC, who can be encompassed by a radiation
port, definitive XRT should have been performed first when possible.

- Individuals who meet the eligibility criteria for EGFR germline mutation testing but
who do not have advanced cancer as defined in 3.1.1 may enroll for EGFR germline
mutation testing only and will not be eligible for the treatment or NOS arms.

- Patients with advanced cancer must meet one of the following criteria (does not apply
to firstdegree relatives or individuals with pre-invasive histology enrolling only
for EGFR germline mutation testing):

- Patients must have biopsiable disease and be willing to undergo biopsy for
molecular profiling

OR

-Patients must have enough and adequate archival material from a previous biopsy to
perform molecular profiling analyses. The adequacy of the material provided will be
determined by the principal investigator in conjunction with the laboratories performing
the molecular profiling analyses

OR

- Patients must have previously undergone a successful molecular profiling of their
tumor with mutation analysis of the genes described in section 5.2, as part of this
protocol (crossover patients) or other molecular profiling protocols such as the Lung
Cancer Mutation Consortium protocol among others.

- Age greater than or equal to18 years.

ELIGIBILITY CRITERIA FOR ENROLLMENT INTO THE TREATMENT ARMS

Please refer to section 3.3 of the protocol for eligibility criteria for enrollment in the
specific molecular profile / treatment arms of this protocol.

INCLUSION CRITERIA:

1. Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as >
20 mm with conventional techniques or as > 10 mm with spiral CT scan.

-Target lesions cannot be selected within previously irradiated areas, if not newly
arising or clearly progressing after irradiation as proven by repeat scanning.

2. Life expectancy of greater than 3 months.

3. Performance status (ECOG) <= 2 (See Appendix C).

4. Patients must have normal organ and marrow function as defined below:

- leukocytes: > 1,500/mcL

- absolute neutrophil count: > 1,000/mcL

- platelets: > 100,000/mcL

- total bilirubin*: < 1.5 times the institutional upper limit of normal

--For patients with Gilbert's syndrome or levels of indirect bilirubin above the
upper limit of normal, direct bilirubin will be used for eligibility and should
be < 1.5 times the institutional upper limit of normal.

- AST(SGOT)/ALT(SGPT): less than 3 times the institutional upper limit of normal

- Creatinine: less than or equal to1.5 times the institutional upper limits of
normal

OR creatinine clearance > 50 mL/min/1.73 m(2) for patients with creatinine levels
above 1.5 times the institutional normal.

5. Patients must have recovered from toxicity related to prior therapy (chemotherapy,
surgery or radiation) to grade <= 1 (defined by CTCAE: The NCI Common Terminology
Criteria for Adverse Events Version 4(CTCAE) will be used for toxicity and adverse
event reporting. All appropriate treatment areas have access to a copy of the CTCAE
version 4.0. A copy of the CTCAE version 4.0 can be downloaded from the CTEP web site
(http://ctep.cancer.gov).

6. The effects of most of the therapeutic agents used in this trial on the developing
human fetus at the recommended therapeutic doses are unknown. For this reason and
because some agents are known to be teratogenic, 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 continue for at least 16 weeks after completing the study to avoid
pregnancy and/or potential adverse effects on the developing embryo. Should a woman
become pregnant or suspect she is pregnant while participating in this study, she
should inform her treating physician immediately. Because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother with targeted therapies, breastfeeding should be discontinued if the mother is
treated with targeted therapies.

7. Ability to understand and the willingness to sign a written informed consent
document.

EXCLUSION CRITERIA:

1. Patients who have had major surgery, chemotherapy or radiotherapy within 2 weeks
prior to entering the study or those who have not recovered from adverse events due
to agents administered more than 2 weeks earlier.

2. Patients may not be receiving any other investigational agents or other medications
for the treatment of their malignancy.

3. Patients with symptomatic brain metastases should be excluded from this clinical
trial because of their poor prognosis and because they often develop progressive
neurologic dysfunction that would confound the evaluation of neurologic and other
adverse events. However, patients who have had treatment for their brain metastases
and whose brain metastatic disease status has remained stable for at least 1 week
after the end of brain radiation may be enrolled to undergo molecular profiling at
the discretion of the principal investigator. In addition, brain metastatic disease
should be stable for at least 4 weeks, before the patients can be enrolled in any of
the experimental treatment arms.

4. Patients with any condition (e.g., gastrointestinal tract disease resulting in an
inability to take oral medication or a requirement for IV alimentation, prior
surgical procedures affecting absorption, or active peptic ulcer disease) that
impairs their ability to swallow and retain tablets are excluded.

5. Any uncontrolled medical illness that precludes the patient from undergoing a biopsy
for molecular profiling and / or receiving treatment under one of the experimental
arms of the study should be excluded. These conditions include but are not limited
to:

- Ongoing or uncontrolled, symptomatic congestive heart failure (Class III or IV
as defined by the NYHA functional classification system (see Appendix D).

- Uncontrolled hypertension

- Unstable angina pectoris

- Cardiac arrhythmia

- Uncontrolled diabetes

- Uncontrolled psychiatric illness/social situations that would limit compliance
with study requirements.

6. Patients with QTc prolongation (defined as a QTc interval equal to or greater than
500 msec) or other significant ECG abnormalities are excluded.

7. Caution should be used if patients are required to use a concomitant medication that
can prolong the QT interval and efforts should be made to switch to a different
medication before the patient begins treatment under an experimental arm. See
Appendix E for a table of medications with the potential to prolong the QTc interval.
A comprehensive list of agents with the potential to cause QTc prolongation can be
found at: http://www.azcert.org/medical-pros/drug-lists/bycategory.cfm

8. The eligibility of patients taking medications that are potent inducers or inhibitors
of that enzyme will be determined following a review of their case by the Principal
Investigator. (A list of potent CYP3A4 inducers or inhibitors can be found in
Appendix F). Every effort should be made to switch patients taking such agents or
substances to other medications before they begin treatment with one of the
experimental drug included in this protocol, particularly patients with gliomas or
brain metastases who are taking enzyme-inducing anticonvulsant agents. A
comprehensive list of medications and substances known or with the potential to alter
the pharmacokinetics of sunitinib through CYP3A4 is provided in Appendix F.

9. Patients with tumor amenable to potentially curative therapy as assessed by the
investigator.

10. Pregnant women are excluded from this study because many of the FDA approved agents
and investigational agents in this trial have the potential for teratogenic or
abortifacient effects. Because there is an unknown but potential risk for adverse
events in nursing infants secondary to treatment of the mother with these agents,
breastfeeding should be discontinued if the mother is treated in this protocol. These
potential risks may also apply to other agents used in this study.

SPECIFIC ELIGIBILITY CRITERIA FOR ENROLLMENT IN TREATMENT ARMS

The following is a description of the eligibility criteria required to be enrolled in the
specific molecular profile based treatment arms of this study which include: Erlotinib,
AZD6244, MK-2206, Lapatinib and Sunitinib arms. This is in addition to the general
eligibility and exclusion criteria described in sections 3.1 and 3.2.

ERLOTINIB ARM

INCLUSION CRITERIA:

1. Patients must have an EGFR TKI sensitizing mutation as determined by analysis of the
primary tumor or a metastatic site in a CLIA certified laboratory.

2. Patients with SCLC or thymic malignancies must have been treated with at least 1
previous standard of care chemotherapy regimen or refuse to be treated with
conventional chemotherapy agents.

EXCLUSION CRITERIA:

1. Previous anti-EGFR TKI therapy

2. Patients with a known EGFR TKI resistant mutation.

3. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to Erlotinib.

AZD6244 ARM

INCLUSION CRITERIA:

1. Patients must have one of the following as determined by analysis of the primary
tumor or a metastatic site in a CLIA certified laboratory:

- KRAS mutation or

- NRAS mutation or

- HRAS mutation or

- BRAF mutation

2. Patients must have been treated with at least 1 previous standard of care
chemotherapy regimen or refuse to be treated with conventional chemotherapy agents.

EXCLUSION CRITERIA:

1. Any prior exposure to MEK, Ras, or Raf inhibitors .

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

3. Cardiac conditions as follows:

- Uncontrolled hypertension (BP greater than or equal to 150/95 despite optimal
therapy)

- Heart failure NYHA Class II or above (See Appendix D)

- Prior or current cardiomyopathy

- Baseline LVEF less than or equal to 50%.

- Atrial fibrillation with heart rate > 100 bpm

- Unstable ischaemic heart disease (MI within 6 months prior to starting
treatment, or angina requiring use of nitrates more than once weekly).

4. Laboratory values as listed below (SI units):

- Absolute Neutrophil Count (ANC) < 1.5x109/L (1500 per mm(3))

- Platelets < 100x109/L (100,000 per mm(3))

- Hemoglobin (Hgb) < 9.0 g/dL

- Serum bilirubin > 1.5 times the upper limit of normal (ULN)

- Aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT) >
2.5 times the ULN (greater than or equal to 5 ULN in presence of liver
metastases).

MK2206 ARM

INCLUSION CRITERIA:

1. Patients must have one of the following as determined by analysis of the primary
tumor or a metastatic site in a CLIA certified laboratory:

- PI3KCA mutation or

- PI3KCA gene amplification by FISH (gene to chromosome ration > 2) or

- AKT mutation or

- PTEN mutation

2. Patients must have been treated with at least 1 previous standard of care
chemotherapy regimen or refuse to be treated with conventional chemotherapy agents.

EXCLUSION CRITERIA:

1. Previous AKT inhibitor therapy.

2. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to MK-2206.

3. Preclinical studies demonstrated the potential of MK-2206 for induction of
hyperglycemia in all preclinical species tested. Patients with diabetes or in risk
for hyperglycemia should not be excluded from trials with MK-2206, but the
hyperglycemia should be well controlled on oral agents before the patient enters the
trial.

LAPATINIB ARM

INCLUSION CRITERIA:

1. Patients must have one of the following as determined by analysis of the primary
tumor or a metastatic site in a CLIA certified laboratory:

- ERBB2 mutation or

- ERBB2 gene amplification by FISH (gene to chromosome ration > 2)

2. Patients must have been treated with at least 1 previous standard of care
chemotherapy regimen or refuse to be treated with conventional chemotherapy agents.

EXCLUSION CRITERIA:

1. Previous Lapatinib therapy.

2. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to lapatinib.

3. LVEF < 50%

SUNITINIB ARM

INCLUSION CRITERIA:

1. Patients must have one of the following as determined by analysis of the primary
tumor or a metastatic site in a CLIA certified laboratory:

- PDGFR-A mutation or

- PDGFR-A gene amplification by FISH (gene to chromosome ration > 2) or

- KIT mutation

2. Patients must have been treated with at least 1 previous standard of care
chemotherapy regimen or refuse to be treated with conventional chemotherapy agents.

EXCLUSION CRITERIA:

1. Previous sunitinib therapy

2. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to sunitinib.

3. Patients who require use of therapeutic doses of coumarin-derivative anticoagulants
such as warfarin are excluded. Note: Low molecular weight heparin is permitted
provided the patient's PT INR is < 1.5.

4. Patients with any of the following conditions are excluded:

- Serious or non-healing wound, ulcer, or bone fracture.

- History of abdominal fis...