University of Michigan Clinical Sequencing Exploratory Research (CSER)

Overview. The personalization of therapy for cancer will require molecular characterization of unique and shared genetic aberrations. In particular, patients who have a sarcoma or other rare cancers and are candidates for clinical trials could potentially benefit by identifying eligibility for "targeted" drugs based on the "actionable" genes in their specific tumor. Growing technological advances in genomic sequencing has now made it possible to consider the use of sequence data in a clinical setting. For instance, comprehensive testing that includes whole exome and transcriptome sequencing may identify biomarkers for predictive or prognostic purposes and thereby inform treatment choices and prevention strategies. Thus, the translation of high throughput next generation sequencing would support a "personalized" strategy for cancer. However, the translation of clinical sequencing bears unique challenges including identifying patients who could benefit, developing informed consent and human subjects protections, outlining measurable outcomes, interpreting what results should be reported and validated, and how results should be reported. In addition, we know very little about how patients and clinicians will respond to the potentially confusing and overwhelming amount of information generated by genomic sequencing, and we lack model processes for clinically evaluating and presenting these data. For the promise of our innovative biotechnologies to be realized, "translational genomics" research that evaluates genomic applications within real-world clinical settings will be required. This proposal brings together expertise at the University of Michigan including clinical oncology, cancer genetics, genomic science/bioinformatics, clinical pathology, social and behavioral sciences, and bioethics in order to implement this clinical cancer sequencing project. Three integrated Projects have the following themes: Project 1) "Clinical Genomic Study" will identify patients with a rare cancer (i.e., 15 out of 100,000 individuals per year) who are eligible for clinical trials, consent them to the study, obtain biospecimens (tumor tissue, germline tissue), store clinical data, and assemble a multi-disciplinary Sequencing Tumor Board to deliberate on return of actionable or incidental genomic results; Project 2) "Sequencing & Analysis" will process biospecimens and perform comprehensive sequencing and analysis of tumors to identify point mutations, copy number changes, rearrangements/gene fusions, and aberrant gene expression; Project 3) "Ethics & Psychosocial Analysis" will observe the expert review process for evaluating sequence results and will examine the clinician and patient response to the informed consent process, delivery of genomic sequence results, and use of genomic results.

• Study Design:
  • Case Set
• Study Type:
  • Case Set
• Total number of consented subjects: 602
• Subject Sample Telemetry Report (SSTR)

5.0 ELIGIBILITY
5.1 Patient population
This protocol is designed to collect biospecimens with annotated clinical data from patients with advanced or refractory cancer.

5.2 5.2 Inclusion Criteria: (Must satisfy all criteria and either #3 or #4)

1. A histologically or cytologically confirmed diagnosis of cancer
2. Patients with any advanced or refractory malignancy
3. Patients are undergoing standard of care surgeries or procedures where specimens will be first used for routine pathologic assessment and only then will leftover tissue be used for research purposes
   OR
4. Patients must have tumor suitable for biopsy (as assessed by trained specialists in interventional radiology) and Patients are medically fit to undergo a tissue biopsy or surgical procedure to get tumor tissue OR If Patients do not have a tumor suitable for biopsy but have another tissue available for molecular evaluation
5. Older than or equal to 18 years of age
6. Procedure-specific signed informed consent prior to initiation of any study-related procedures
7. Women and minorities are included in this protocol
8. Patients with multiple malignancies remain eligible
9. Patients with an inherited cancer syndrome or a medical history suggestive of an inherited cancer syndrome remain eligible

5.3 Exclusion Criteria:

1. It is the enrolling study physician's discretion to decide if a patient is not fit enough to undergo tissue biopsy
2. Patients who are incarcerated are not eligible to participate
3. Women who are pregnant

5.4 Women of childbearing age
For women of childbearing age, there are no screening requirements. We note that most patients entering this study are seeking eligibility for therapy or other clinical trial, in which case they are generally asked to avoiding becoming pregnant and even exercise some form of contraception by their medical oncologist. For women of childbearing age, their referring medical oncologist will discuss necessity or role for appropriate contraception. This is not part of the study activity, nor is it required for participation.

• Primary Phenotype: Neoplasms
• Breast Neoplasms
• Sarcoma
• Prostatic Neoplasms
• Aromatase Inhibitors

• Principal Investigator
  • Arul Chinnaiyan, MD PhD. Michigan Center for Translational Pathology, University of Michigan, MI, USA.
• Funding Source
  • 1UM1HG006508. NHGRI, NCI, National Institutes of Health, Bethesda, MD, USA.