Biomarker Analysis for Patients With Metastatic Colorectal Cancer (MCC)

This is a short-term, prospective, feasibility study to determine how effectively
investigators can obtain biomarker analysis on patients with mCRC from whom informed consent
and authorization will be obtained. The study will be done in partnership with Quintiles.
Investigators will be collecting data on the number of clinically actionable biomarkers that
can be detected in each population and the number of trial actionable markers that can be
detected in these populations. Patients with recurrent metastatic disease (ie, first
diagnosis of metastatic disease following resection, last radiation, or last chemotherapy in
the adjuvant setting) will have their primary specimen sent for a biomarker analysis.
Actionable markers or genomic alterations will be FDA-approved companion diagnostic markers
and markers used for trial enrollment in metastatic colorectal cancer. Additional
information regarding FDA-approved companion diagnostic markers and markers used for trial
enrollment in indications other than mCRC will also be collected and reported.

Biospecimens from 25 patients who have had early recurrence (≤ 12 months) and 25 patients
who have had late recurrence (> 12 months) of their metastatic colorectal cancer will be
appropriately collected, processed, shipped, and tested. The frequency and sites of mutation
may be hypothesis generating to help identify those patients at higher risk for early
recurrence and aid in identifying future treatment options and in selecting better treatment
options for this poor prognostic group.

REGISTRATION PROCEDURES Written documentation of full, noncontingent IRB approval must be on
file before a patient can be registered. The registration process begins when the
coordinator has obtained a signed informed con-sent. Patient demographics will be into the
Clinical Trial Management System (CTMS); this is the Web-based intranet system for the
delivery of trial information across USOR. A unique patient number (UPN) will be assigned to
the patient at that time. Entering a patient into CTMS does not signify that the patient has
been registered in the study.

Once the patient has a UPN number, the coordinator can go to the Patient Report and select
the patient to be registered. Located to the left of the patient's UPN will be the letters
"Reg" in blue. The coordinator will click on the blue "Reg" to open up that patient's
information. Each page that needs to be completed will be in yellow. The site will answer
the questions on the Inclusions, Exclusions, and Prestudy Assessment pages. Once all
questions on each page are answered, that page will turn green. An ID number and study arm
will be directly assigned.

SAMPLE PROCUREMENT PROCEDURES USOR study sites will be supplied with tumor collection kits
through the US Oncology Investigational Product Center (IPC).

Biospecimens will have a date of shipment within 4 weeks of the patient signing the consent
in order to be enrolled in the study. Tissue will be sent to a central laboratory. Details
for shipping will be provided in the Clinical Trials Information (CTI) provided separately
by USOR.

Reference laboratory manual for tissue preparation and shipment instructions.

SAMPLE ANALYSIS AND CONFIDENTIALITY It is the intention of USOR and Quintiles that patient
confidentiality will be maintained throughout the procedure. USOR maintains rigorous
standards of confidentiality for clinical studies by coding samples with patient initials
and a unique identifier (UPN number/patient/study ID number) and study number. A patient is
in screening upon signing the ICF and registered in CTMS. A patient will be considered
enrolled in the study if a standard of care biospecimen is available for biomarker testing
with a shipment date within 4 weeks of ICF signature. If a standard of care biospecimen is
unavailable, for any reason, within 4 weeks the patient is deemed a screen failure.

BIOSPECIMEN ASSESSMENT High throughput sequencing utilizing the Life Technologies Ion
Torrent platform or similar alternative will be used. This methodology provides
high-quality deep sequencing coverage ideally suited for SNP detection and mutational
analysis. Point mutation identification analysis will include targeted whole exome
sequencing of tumor tissue that will cover several hundred human protein-coding exons.
Results from the profiling will be compiled and arranged according to relevancy to clinical
practice. All clinically actionable results will be provided back to the physician using the
same identifiers referenced above.

SAMPLE TESTING FAILURES Samples submitted for analysis will be from archived FFPE tissue.
Ability to perform the AmpliSeq testing may be limited based on the quality and quantity of
the sample available. Reasons for testing failures may be due to an inability to extract
sufficient quality and quantity of DNA, inability to create a sequencing library or
inability for a sample to sequence. Should a testing failure occur, the reason for the
testing failure will be recorded by the laboratory and reported back to the clinician. A
patient will have the opportunity, in discussion with their study physician, dependent on
space in the study and approval from the US Oncology Clinical Project Manager, be allowed to
re-submit one additional sample for sequencing. If a sample from a patient is a testing
failure after 2 testing attempts, the patient is considered a permanent testing failure and
will not be offered an opportunity to submit any additional samples.

Inclusion Criteria:

1. Has been re-staged to Stage IV colorectal cancer following recurrence after adjuvant
chemo-therapy treatment for Stage II or III disease

2. Primary tumor has been resected prior to the patient being diagnosed with Stage IV
disease

3. Able to submit archival tissue from the patient's resected primary tumor taken prior
to diagnosis of metastatic disease

4. Tumor tissue (biopsy or surgery) was retrieved within 4 weeks from the date of
signing the ICF and tested as outlined in the protocol:

• FFPE specimen (blocks or cut slides) currently in storage at a pathology lab. Such
tissue may be archival and stored, for no more than 5 years, being obtained at the
time for a standard of care diagnostic or research biopsy.

5. Is at least 18 years old

6. Is willing to allow access to clinical and demographic information

7. Has signed a Patient Informed Consent Form

8. Has signed a Patient Authorization Form (HIPAA)

Exclusion Criteria:

1. Is unable or unwilling to provide informed consent for collection and profiling of
tumor tissue

2. PATIENT HAS NOT RECEIVED PRIOR ADJUVANT TREATMENT FOR STAGE II OR III COLORECTAL
CANCER OR HAS BEEN ORIGINALLY DIAGNOSED WITH STAGE IV