UC-GENOME: Urothelial Cancer-GENOmic Analysis to iMprove Patient Outcomes and rEsearch

OUTLINE: This is a multi-center study.

STUDY PLAN:

SUBJECT IDENTIFICATION AND CONSENT:

Sites may approach all subjects who attend an appointment for evaluation of metastatic
urothelial cancer for inclusion. Study staff review consent documents with potential subjects
and answer any and all questions. If a subject desires additional time or wishes to delay
enrollment in the study, he/she is given a copy of the consent document and informed about
how to ask questions or enroll at a later date. If the subject chooses to participate in the
study, he or she signs the consent, and is given a copy for his or her own records.

BIOSPECIMEN COLLECTION AND PROCESSING:

When subjects are consented for entry into this study, they consent to access of any archival
tumor tissue (whether from the primary or any metastatic site) for genetic analysis. This
tissue is not de-identified at the time of testing so that a subject specific report may be
generated and sent to the treating physician. Further, subjects consent to the indefinite use
of their specimens and linked clinical information for ongoing or future biomedical research.
Additionally, sites inform subjects during the consent process that researchers may use their
information for genetic research including research on somatic or germline mutations. The
specimens and report provided to HCRN are de‐identified and future analyses will be performed
on coded (de-identified) data/specimens.

Collection of Archived Tumor Samples:

- After the subject is consented, sites will request primary and/or metastatic archived
tumor tissue. The tissue specimen sent may come in the form of a block or slides. Needle
biopsy is also acceptable.

- Each institution can use its own standard operating procedure for the preparation of the
FFPE material. Each participating site will ship specimens accessed under GU15-217
directly to the lab performing the NGS analysis. Sites will also request corresponding
pathology report(s). A de-identified pathology report will then be sent to HCRN with the
tissue.

Collection of Blood for Research Purposes Only:

- Each subject will have 47 mL of blood collected and banked for future testing. 10mL of
the sample will be used for plasma for banking. 17 mL of the sample will be used for
PBMC isolation and cryopreservation. 20mL of the sample will be used for plasma for
cfDNA. Any DNA analysis of blood (including possible germline analysis) is for research
purposes only and will be performed on coded (de-identified) samples.

Report Generation:

- The subject specific report generated includes a summary of genomic alterations
highlighting those variations considered potentially actionable, a concise discussion of
the molecular analyses, a list of potential clinical trials incorporating relevant
targeted agents, and potential therapeutic options based on the specific alterations
discovered along with associated levels of evidence for each. The selection of clinical
trials and levels of evidence provided are based on extensive review and analysis of the
literature as well as a BCGC convened panel of experts in bladder cancer. This BCGC
expert panel will work with the NGS lab to ensure that all potential clinical trials are
represented in the individual subject reports.

Storage for Future Research:

- The BCAN Biobank at Hoosier Cancer Research Network (HCRN) will store DNA and RNA
isolated for the study, additional FFPE and any biospecimens remaining after the NGS. If
at any point a subject wishes to withdraw from the study, the subject will contact their
study physician. HCRN will destroy any specimens that it may link to the subject. Once
specimens have been stripped of all identifying information or links to identifying
information they cannot be recalled to be destroyed.

COMMUNICATION OF NGS RESULTS TO PROVIDER AND SUBJECT:

After NGS testing is complete, a subject specific report will be provided to the subject's
treating physician either in hard copy and/or via on-line portal (typically within 14
business days from receipt of tumor tissue) and a de-identified report to HCRN. If an
addendum is made to a report, an updated report will be provided to the treating physician
and HCRN in the manner described above. During the informed consent process, sites inform
each subject that his or her physician will communicate results of the genetic testing on
their tumor specimens. Along with the results that are communicated, the subjects' treating
physician will explain the implications of their testing results, including whether their
genetic profiles render them potentially eligible for a specific therapy or clinical trial.

Sites also inform subjects that researchers will store any specimens remaining after genetic
profiling of their tumor is complete. Storage continues indefinitely for future biomedical
research. This may include development of commercial products from their specimens.

Sites must explain to subjects that although a blood sample is being obtained, this study is
not aimed at discovering germline mutations. Sites must emphasize that genetic analyses
performed within this study should not be construed as genetic testing for genetic mutations
associated with hereditary cancer susceptibility. Nevertheless, because NGS may be performed
on blood, it is possible that a germline mutation that predisposes a subject to cancer will
incidentally be discovered. Subjects will not receive any information about such mutations,
however, as this analysis will be performed on de-identified samples.

ABSTRACTION OF MEDICAL RECORDS:

Research staff at each site abstracts clinical information from each subject and enters the
information into the web based clinical research platform (EDC system). Data abstracted
includes details on the following: demographics, cancer diagnosis, cancer stage, surgical and
medical management, any treatment decisions made in response to the NGS results communicated
to the physician and any response/longer term outcome data as a result of these treatment
decisions.

ACCESS TO DATA/SPECIMENS FOR FUTURE RESEARCH:

The database links coded clinical and genetic data, creating a biospecimen and data
repository. These data, along with biospecimens stored at HCRN, will ultimately be available
for researchers with BCGC-approved and IRB-approved studies allowing access to these
data/specimens, and with HCRN managing the data, protecting the confidentiality of study
subjects.

Inclusion Criteria:

Subjects must meet all of the following applicable inclusion criteria to participate in
this study:

- IRB-approved written informed consent and Health Insurance Portability and
Accountability Act of 1996 (HIPAA) authorization for release of personal health
information; NOTE: HIPAA authorization may be included in the informed consent or
obtained separately.

- Age ≥ 18 years at the time of consent.

- Histologically or cytologically confirmed urothelial cancer of the bladder, urethra,
ureter, or renal pelvis.

- Metastatic urothelial cancer as defined by M1 (distant metastatic disease) and/or N3
(nodes outside of the true pelvis) at the time of registration.

- Tumor tissue available and suitable for molecular analyses from at least one of the
following sources:

- Tissue previously stored at enrolling institution

- Tissue previously stored at an outside institution (other than enrolling
institution)

- The tissue specimen may come in the form of a block or slides accessed under UC-GENOME
from enrolled subjects. Needle biopsy is also acceptable. Details regarding collection
requirements, processing and shipping can be found in the Correlative Laboratory
Manual (CLM).

- Willing to provide access to tissue and blood for future research, including genetic
studies.

Exclusion Criteria:

Subjects meeting any of the criteria below may not participate in the study:

- Unwilling or unable to provide informed consent.

- Affected by dementia, altered mental status, or any psychiatric or co-morbid condition
that would prohibit the understanding or rendering of informed consent, as determined
by treating physician.