IMPACT 2: Randomized Study Evaluating Molecular Profiling and Targeted Agents in Metastatic Cancer

If you agree to take part in this study, a sample of tumor tissue will be collected as part
of a biopsy. The type of biopsy you receive will depend on the disease site. The study doctor
will describe the procedure and its risks to you before the biopsy.

If you have tumor tissue available from a procedure performed within the last year and you
have received no anti-cancer therapy since that time, samples from this procedure may be able
to be used for molecular profiling. In this case, you would not need to have a biopsy. The
study doctor will discuss with you whether your leftover sample can be used.

The tumor tissue will be sent to Foundation Medicine for molecular profiling. Then, the
results will be used to determine if there is a genetic abnormality for which a targeted
therapy is available. The planned time to get this information is 3 weeks, or possibly longer
if needed. As with other cancer studies, this may take more time to determine. If you have
previously untreated cancer your doctor may treat you with standard therapy, excluding
targeted therapy. In this case, results of your molecular profiling will be used for further
treatment if your disease gets worse.

A) If there is no abnormality, your doctor will treat you according to what he/she thinks is
in your best interest. The results of molecular profiling will be given to you at the time
the results become available.

B) If there is an abnormality and there is an FDA-approved drug for the tumor type, you will
be offered that treatment. The results of molecular profiling will be given to you at the
time the results become available.

C) If there is an abnormality and there is no FDA-approved drug for the abnormality and the
tumor type, you will then be randomly assigned (as in the flip of a coin) to 1 of 2 study
groups.

You will have an equal chance of being assigned to either group:

- If you are in Group 1, you will receive a targeted therapy against the abnormality.

- If you are in Group 2, you will receive a standard-of-care therapy.

Neither you nor your study doctor will be able to choose to which group you are assigned. The
results of molecular profiling will be given to you before you are randomly assigned to a
treatment group. If at any point the disease appears to get worse, you will be able to cross
over to the other study group and be assigned to that therapy.

Blood (about 2 teaspoons) will be drawn to look for genetic changes in your blood.

All Patients:

The therapy you will receive may consist of either a commercially available drug/therapy or a
clinical study in which you will be asked to be enrolled. In either case, the disease will be
followed as part of the standard of care (imaging scans, blood draws, biopsies, and so on).
These procedures will not be performed as part of this study. However, their results and
other entries in your medical record will be checked as part of this study to learn if the
disease is getting worse, getting better, or staying the same.

Length of Study:

Your medical records and your health will continue to be reviewed from the time that you sign
this consent until any time that the disease appears to get worse (unless you cross over to
another study group).

Inclusion Criteria:

1. Patients with metastatic cancer.

2. Patients may have received unlimited lines of prior therapy.

3. Prior to randomization, patients with metastatic disease must have been treated with
established standard-of-care therapy, or physicians have determined that such
established therapy is not sufficiently efficacious, or patients have declined to
receive standard-of-care therapy.

4. The patient has measurable disease.

5. The patient has Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

6. The patient has biopsy-accessible tumor. For patients who had no prior anticancer
therapy and had surgical resection within a year and tumor tissue is immediately
available, that tumor will be analyzed and no biopsy will be needed.

7. The patient has normal organ and marrow function, defined as absolute neutrophil
count>/= 1,000/µl; platelets >/=100,000/µl (unless these abnormalities are due to bone
marrow involvement).

8. The patient has adequate hepatic function as defined by a total bilirubin level x the upper limit of normal (ULN), unless the patient has known Gilbert's disease, and
alanine aminotransferase (ALT)/ serum glutamic pyruvic transaminase levels (SGPT) 2.5 X ULN (unless the patient has liver metastases).

9. The patient has serum creatinine clearance >/= 50 ml/min by the Cockcroft-Gault
formula.

10. If the patient has brain metastasis, they must have been stable (treated and/or
asymptomatic) and the patient must have been off steroids for at least 2 weeks.

11. The patient is >/=18 years of age.

12. The patient has provided signed informed consent.

13. Patients with a previous malignancy (other than the patients' known cancer) that were
treated successfully and are disease-free for at least 3 years are allowed.

14. Patients with a history of basal cell carcinoma of the skin or pre-invasive carcinoma
of the cervix are eligible.

15. Women of childbearing potential 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. Childbearing potential will be defined as women who have had
menses within the past 12 months and who have not had a tubal ligation, hysterectomy,
or bilateral oophorectomy. Should a woman become pregnant or suspect that she is
pregnant while participating in this study, she should inform her treating physician
immediately.

16. Male subjects must agree to use effective contraception or abstinence while on study
and for 90 days after last dose of study drug.

Exclusion Criteria:

1. Patients who are randomized to the control arm must not receive therapy based on prior
molecular profiling.

2. The patient has received chemotherapy, surgery, or radiotherapy (for therapeutic
purposes) within 3 weeks of initiating study treatment (4 weeks for bevacizumab or
investigational drugs) or the patient has not recovered (grade ≥2 from side effects of
the previous therapy). Patients who receive palliative radiation therapy can be
treated immediately after completion of radiation therapy.

3. The patient has cardiac conditions as follows: uncontrolled hypertension (BP >
160/100) despite optimal therapy, uncontrolled angina, ventricular arrhythmias,
congestive heart failure (New York Heart Association Class II or above), prior or
current cardiomyopathy, 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. The patient has peripheral neuropathy >/= grade 2.

5. The patient is pregnant (confirmed by serum b-HCG, if applicable) or is breastfeeding.

6. The patient has concurrent severe and/or uncontrolled medical disease that could
compromise participation in the study (i.e., uncontrolled diabetes, severe infection
requiring active treatment, severe malnutrition, chronic severe liver or renal
disease).

7. The patient has refractory nausea and vomiting or chronic gastrointestinal diseases
(e.g., inflammatory bowel disease) or has had significant bowel resection that would
preclude adequate absorption (for oral therapy only).

8. The patient is unable to swallow capsules and/or has a surgical or anatomical
condition that precludes swallowing and absorbing oral medication on an ongoing basis
(for oral therapy only).

9. Any other condition that would, in the investigator's judgment, contraindicate the
patient's participation in the clinical study due to safety concerns or compliance
with clinical study procedures.