UC-GENOME: Urothelial Cancer-GENOmic Analysis to iMprove Patient Outcomes and rEsearch: Hoosier Cancer Research Network GU15-217
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.
Trial of Strategies to Communicate Genetic Information to Different Ethnic and Racial Subpopulations
Any patient referred to the breast cancer and genetic risk counseling clinics in either of
the two sites will be eligible to participate as long as they meet the inclusion and
exclusion criteria. The research assistant in each site will meet with the patients and
explain about the study goals and procedures and ask them to participate in the study. Those
interested will be enrolled into the study after obtaining informed consent. For those who
refuse to participate, reasons for refusal will be requested and catalogued. All study
participants will be followed and the study measures will be tracked at Days 0, 30, 180 and
365. In addition, health care utilization (ER Visits, Hospitalizations, clinic visits,
screening tests and procedures) will be tracked both through the electronic medical records
and patient interviews (as some patients may seek care in other hospitals for emergencies
etc.). Investigators currently do follow-up phone interviews routinely with our patients.
Study measures will be administered as described above. For those who drop out from the
study, reasons for withdrawal from the study will be explored and catalogued.
Procedures for Treatment Compliance and Treatment Non-completers:
(i) Compliance Procedures: Investigators will monitor degree of compliance with whether study
measures were completed on Days 0,7,30 & 365 intervention. Analyses will be done following
the intent-to-treat principle.
(ii) Treatment Non-completers: For those who drop out from the study after Day 0, reasons for
withdrawal from the study will be explored and catalogued. They will be asked for feedback
about the study intervention and satisfaction with the experience (or the lack thereof).
Procedures for Data Collection: The participants will have the option of submitting the data
in person or by phone to the project research associate. The PI will meet with the study
personnel at least on a weekly basis to continuously monitor their performance and to ensure
adherence to study methodology.
There are risks, discomforts, and inconveniences associated with any research study. These
deserve careful thought. Participants should talk with the Protocol Director for any
questions. Risks of answering the survey instruments and interview questions are minimal and
may occasionally cause distress.
Audio recording of the patient interviews. Investigators will create verbatim transcripts to
be analyzed using qualitative methods. Recordings will be stored for a period of 20 years and
then erased.
Immune Checkpoint Inhibitor Toxicity (I-CHECKIT): A Prospective Observational Study
PRIMARY OBJECTIVE:
I. To both develop and independently validate a risk prediction model for Common Terminology
Criteria for Adverse Events (CTCAE) grade 3 or higher non-hematological immune-related
adverse events (irAEs) in the first year of immune checkpoint inhibitor (ICI)-based therapy
for the treatment of solid tumors.
SECONDARY OBJECTIVES:
I. To prospectively assess the incidence of any grade of non-hematological irAEs and grade 4
hematological irAEs on ICI-based therapy.
II. To observe the trajectory of patient-reported quality of life and health preferences over
12 months.
III. To observe the trajectory of patient-reported adverse events over 12 months using serial
assessment with select Patient-Reported Outcomes version of the Common Terminology Criteria
for Adverse Events (PRO-CTCAE) measures.
IV. To measure the burden of chronic, grade 1 and 2 toxicities using methods such as toxicity
over time (ToxT).
V. To track patterns of treatment of irAEs and patterns of toxicity resolution.
TRANSLATIONAL MEDICINE OBJECTIVES:
I. To evaluate the cytokine toxicity (CYTOX) score, a composite measure derived from 11
different cytokine levels, both prior to ICI-based therapy and after 1 cycle of ICI-based
therapy as a predictive signature for the development of irAEs.
II. To establish a repository of archival tissue and blood/serum specimens for potential
predictive and/or prognostic markers of irAE risk.
ADDITIONAL OBJECTIVE:
I. To assess the feasibility of using electronic (e)PRO in a multi-center clinical trial
setting.
OUTLINE:
Patients undergo collection of a tissue sample at the start of their routine cancer
treatment. Patients complete questionnaires at the start of cancer treatment, weeks 4, 12,
24, and 52. Patients will have the option of providing blood samples at several time points
during the study.
Blue Light Cystoscopy With Cysview® Registry
Data will be captured on specific patient types undergoing Blue Light Cystoscopy with Cysview
for known or suspected non-muscle invasive bladder cancer. Specific clinical questions will
be asked.
1. What is the incremental detection rate with Blue Light Cystoscopy with Cysview over
conventional white light cystoscopy in each of the seven (7) patient populations? Does
this translate into lower recurrence/progression rate?
2. How do the six (6) tumor variables used in the European Association of Urology (EAU)
risk tables (primary/secondary, recurrence rate, size, multifocality, grade, and history
of carcinoma in situ (CIS))6 affect this incremental rate?
3. How does an abnormal cytology or positive or negative fluorescent in situ hybridization
(FISH) affect the likelihood that Blue Light Cystoscopy with Cysview will detect more
cancers than white light?
4. What are the performance characteristics of Blue Light Cystoscopy with Cysview within
eight (8) weeks of Bacillus Calmette-Guérin (BCG) with respect to improved tumor
detection and false positive rate compared to conventional white light cystoscopy?
5. What is the incremental Blue Light Cystoscopy with Cysview detection rate over random
bladder biopsies alone in patients being evaluated for routine three month restaging
(group 4) or occult disease (group 5)?
6. What are the performance characteristics of Blue Light Cystoscopy with Cysview after
repeated Blue Light Cystoscopy with Cysview evaluations with respect to improved tumor
detection, false positive rate and safety compared to conventional white light?
7. Does an abnormal urinalysis help identify patients with inflammation more likely to have
false positive Blue Light Cystoscopy with Cysview results?
8. What is the practical learning curve for becoming "proficient" with Blue Light
Cystoscopy with Cysview?
9. What is the overall false positive rate with Blue Light Cystoscopy with Cysview?
10. Can Blue Light Cystoscopy with Cysview make the resection more complete? If yes, is this
due to improved margins and/or additional tumors seen under blue light?
The Blue Light Cystoscopy with Cysview Registry is a web-based program supported by Global
Vision Technologies. Data will be captured longitudinally over five (5) years on patients
from each enrolled site. Each center will enter their respective site's patient data
electronically.
Proleukin Observational Registry to Evaluate the Treatment Patterns and Clinical Response in Malignancy
The PROCLAIM Registry is a US-based, multicenter Registry designed to establish a high
quality observational database of real-world clinical data on HD IL-2 when used to treat
patients with mRCC, mM or other malignancies. The Registry will not, in any way, suggest
changes in the treatment or management of the patients enrolled in the Registry. Therefore,
physicians will continue to manage and treat patients according to standard of care and their
own judgment.
The PROCLAIM Registry will start with a retrospective pilot data collection from a
de-identified finite number of patient cases abstracted from their existing medical charts.
The features collected will be identical to those planned for the prospective registry. The
resulting database will be used to formulate hypotheses to be tested using the prospective
registry database. Patients utilized in the retrospective analysis will be excluded from the
prospective portion of the Registry.
In the prospective portion of the Registry, sites will enroll patients who are expected to
start a course of HD IL-2 therapy. Once enrolled, the patient must receive at least one dose
of HD IL-2 to remain in the Registry. Patients will be treated and followed according to the
site's standard of care. This Registry will in no way induce changes in the management of
individual patients. Clinical data features will be entered into an Electronic Data Capture
(EDC) system, and organized into a registry database.
The data contained in the registry database will be observational data. The PROCLAIM Registry
does not stipulate patient care, specific visits or interventions but merely surveys
standardized parameters regarding HD IL-2 and associated therapies as they are applied by
treatment centers. The collection of standard data over time permits the evaluation of trends
in patient survival and subsequent therapy exposure. The database will be used to answer
future queries formulated by researchers.
CISTO: Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer
Most bladder cancer patients (74%) present with NMIBC where the cancer is limited to the
lining or support layer of the bladder. High-grade NMIBC is treated initially with endoscopic
resection and intravesical immunotherapy, followed by bladder instillations of BCG. Most
patients with high-risk, high-grade NMIBC are able to retain their bladders and avoid more
invasive treatments. However, 24-61% of patients will have their cancers recur within 12
months of treatment with BCG (BCG failures), and they have limited treatment options.
National guidelines recommend consideration between two alternatives: additional medical
management and radical cystectomy (removal of the bladder). Selecting between these options
involves weighing the risk of progression of bladder cancer and loss of a window of potential
cure versus the risk of morbidity and loss of quality of life (QOL) with bladder removal.
This complex decision-making engages patients and their caregivers, who may be impacted by
the urinary, sexual, and bowel dysfunctions that can occur with NMIBC treatment.
The investigators will evaluate this research question on a large scale in real world
practice settings including academic and community-based practices and examine
patient-centered outcomes. The investigators have engaged stakeholders with diverse
perspectives relevant to this research question, including patients, caregivers, national
patient advocacy organizations, national medical specialty organizations, guideline
developers, health care payers, and industry. By engaging broad expertise relevant to this
research question, the investigators will ensure that the study results will help NMIBC
patients whose cancer recurs after BCG treatment make more informed decisions that improve
the health outcomes that are important to them.
CISTO is an observational study that will not affect the treatment that patients chose.
Patient surveys will occur at study entry and at follow-up assessments for up to four years.
There will also be a qualitative sub-study that will include interviews of approximately 50
patients and 25 caregivers recruited from the observational cohort study.
Clinical Validation of the InterVenn Ovarian CAncer Liquid Biopsy (VOCAL)
This is a prospective, international, multi-center, observational study with a goal of
collecting de-identified samples and data from 1,200 women with a known pelvic mass.
Participants will consent to baseline and follow-up data and biospecimen collections.
Evaluation of Regional Gadolinium Retention in the Brain Using QSM With Correlation to Regional DCE MRI Permeability Using GOCART Technique in Intracranial Neoplasm Patients Receiving Gadobenate Dimeglumine (MultiHance) or Gadoterate Meglumine (Dotarem)
PRIMARY OBJECTIVES:
I. To obtain preliminary data (e.g. mean, variance, distribution) in the regional brain
parenchymal changes associated with gadolinium (Gd) deposition during 8 to 18 months period
after administration of gadolinium based contrast agents (GBCA) to Gd naive intracranial
neoplasm patients who will be randomized to gadobenate dimeglumine (MultiHance) or gadoterate
meglumine (Dotarem).
II. To explore if areas of increased regional Gd deposition at individual level are
correlated with baseline regional DCE permeability metrics such as volume transfer
coefficient reflecting vascular permeability (kTrans), extracellular volume ratio reflecting
vascular permeability (ve) and plasma volume (vp) in intracranial neoplasm patients.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients undergo standard of care QSM and T1 weighted imaging (T1WI). Patients then
receive gadobenate dimeglumine intravenously (IV) and undergo GOCART DCE MRI over 60 minutes.
ARM II: Patients undergo standard of care QSM and T1WI. Patients then receive gadoterate
meglumine IV and undergo GOCART DCE MRI over 60 minutes.
After completion of study, patients are followed up at 8-18 months.
Evaluating Nutritional Preferences and Product Accessibility in Oral Nutritional Supplements for Oncologic Patients - A Cross-Sectional Survey Study at Norris Comprehensive Cancer Center
PRIMARY OBJECTIVES:
I. Identify how patients with cancer are obtaining nutrition to support medical management.
SECONDARY OBJECTIVES:
I. Examine associations of gastrointestinal side effects with specific diagnoses and
respective medical therapies.
II. Understand how patients access information regarding nutritional supplements.
III. Evaluate patient satisfaction with currently available oral nutritional supplements
(ONS).
IV. Identify patient preferences in formulating a novel nutritional supplement.
OUTLINE:
Participants attend an interview over 15 minutes and complete surveys.
Assessing Health Literacy and Interpreter Use in Radiation Oncology at LAC+USC Medical Center
PRIMARY OBJECTIVE:
I. To assess patient health literacy and understanding of critical radiation information
during consultation in Spanish and English speaking patient in the department of radiation
oncology at Los Angeles County (LAC) + University of Southern California (USC) utilizing a
patient survey administered after consultation.
SECONDARY OBJECTIVE:
I. Correlate findings of radiation comprehension and satisfaction with validated measures of
health literacy, acculturation, and socioeconomic status of patients.
TERTIARY OBJECTIVE:
I. To assess patient satisfaction of interpreter service in Spanish-speaking patients among
breast and prostate cancer patients receiving definitive radiation.
OUTLINE:
Patients complete a survey over 5-10 minutes about their understanding of radiation therapy.
Core Biopsies of Breast Tumor Tissue Repository
PRIMARY OBJECTIVES:
I. To develop a baseline and serial breast cancer core biopsy repository within the
University of Southern California (USC)/Norris Comprehensive Cancer Center Women's Cancer
Program.
II. To develop and maintain a secure clinical database of relevant demographic, clinical,
pathologic and longitudinal outcome characteristics of the samples to be banked.
III. To have an efficient process for the distribution of de-identified samples from the bank
to researchers with institutional review board (IRB)-approved protocols or exemptions for the
study of breast cancer-related questions. These studies would include analyses of tumor
proteins and nucleic acids, serum/plasma and germline deoxyribonucleic acid (DNA) and immune
cells in relationship to other baseline and follow-up clinical and pathological variables.
OUTLINE: Patients are assigned to 1 of 4 cohorts.
COHORT I (PATIENTS WITH NEWLY DIAGNOSED EARLY STAGE BREAST CANCER WHO WILL UNDERGO DEFINITIVE
SURGERY BEFORE ANY SYSTEMIC THERAPY): Patients undergo baseline and, if applicable, follow-up
core needle biopsies of breast cancer in the breast, regional nodes, and distant metastases.
Patients who experience a recurrence or progression after therapy undergo additional core
biopsies at the time of recurrence. Clinical and blood specimens will also be gathered.
COHORT II (PATIENTS WITH NEWLY DIAGNOSED BREAST CANCER WHO WILL RECEIVE STANDARD OF CARE
SYSTEMIC THERAPY BEFORE SURGERY OR PATIENTS WITH ADVANCED UNRESECTABLE DISEASE): Patients
undergo core biopsy, clinical, and blood sample collection as in Cohort I. Patients also
undergo biopsies at a specific time point following the initiation of standard systemic
therapy.
COHORT III (PATIENTS BEING EVALUATED FOR A SUSPICIOUS BREAST MASS THAT HAS A HIGH LIKELIHOOD
OF BEING CANCER): Patients undergo core biopsy, clinical, and blood sample collection as in
Cohort I. Patients who have Breast Imaging-Reporting and Data System (BIRADS) 4b, 4c, and 5
lesions may undergo up to 6 additional 6 core biopsies.
COHORT IV (PATIENTS WITH BREAST CANCER RECURRENCE OR PROGRESSION [LOCAL, REGIONAL, OR
DISTANT/METASTATIC]): Patients undergo core biopsy, clinical, and blood sample collection as
in Cohort I. Patients may also undergo 1-3 extra core biopsies.
After completion of study, patients are followed up every 6 months.
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