16M-14-1: Phase 1b/2, Multicenter, Open-label Study of Oprozomib and Dexamethasone in Patients with Relapsed and/or Refractory Multiple Myeloma
Multiple myeloma is a type of blood cancer caused by the transformation and uncontrolled multiplication of plasma cells (a type pf blood cell). It is the second most common hematological malignancy and is invariably fatal. Myeloma cells expand in the bone marrow causing skeletal destruction, high calcium levels, kidney failure and anemia.
The study population will consist of multiple myeloma patients requiring therapy who have relapsed and/or are refractory to their last therapy and have been treated with at least 1, but not more than 5 lines of multiple myeloma therapy.
The study drug, oprozomib works by preventing the breakdown of certain proteins in cells, causing the cells to die. Studies with oprozomib have been able to demonstrate the treatment potential for blocking proteasomes (protein complexes) in multiple myeloma. These proteasomes main function is to degrade unneeded or damaged proteins.
The primary objective of Phase 2 is to estimate the overall response rate.
This study is an open-label, Phase 1b/2, multicenter study in which participants will receive oprozomib administered orally, once daily, in combination with dexamethasone as follows:
Days 1, 2, 8, and 9 of a 14-day cycle;
Treatment will be administered in 14-day cycles until disease progression, unacceptable toxicity, or study treatment discontinuation for any reason.
USC will only participate in Phase 2. The Phase 2 portion of this study will be initiated at the sponsors discretion using the recommended dose determined from 1 or both dosing schedules. The total study duration is expected to be approximately 26 months.
SEPTA Trial: Stockholm3 Validation Study in a Multi-Ethnic Cohort for ProsTAte Cancer
Study Design and Procedures:
The research coordinator will explain the information contained within the consent.
Additionally, patient's blood will be drawn prior to their biopsy.
Prior to the biopsy, blood will be collected in x2 ethylenediaminetetraacetic acid (EDTA) 4
ml tubes after obtaining consent from the subjects. One tube will be immediately centrifuged
(10 minutes at 2000G) and plasma decanted to a tube without additives (this typically
produces 1.5 ml of plasma). The decanted tube (with plasma) and the remaining EDTA tube (with
whole blood) is then frozen and stored at the designated participating institutional site. It
will be stored at -20 Celsius until being shipped. The SEPTA specific blood collection is
followed by the following collaborators: Uropartners, University of Illinois at Chicago,
University of Chicago, Rush Medical Center, Montefiore, University of Texas Health Science
Center of San Antonio, Urology Clinics of North Texas, University of Southern California Keck
School of Medicine, Los Angeles County Hospital, Stanford University.
Additional samples from University Health Network (Toronto), Northwestern Medicine, John H.
Stroger, Jr. Hospital of Cook County, and Cook County Health System (Chicago) will be
included from biobanked sources which were prospective collected meeting inclusion and
exclusion criteria.
Patient data will be stored in a REDCap database, hosted on Sweden's secure server. Data will
be stored for the duration of the study, and 5 years afterwards for data analysis purposes.
Consented patients will be tracked by patient logs by each participating institution. The
medical record number will be collected to keep a consistent identifier for data collection
by key site personnel. Once all the patient data is recorded the data will be exported from
REDCap with the MRN removed. There will be no patient identifiers used at the Karolinska
Institute or A3P lab. The following PHI and non-PHI information will be logged of the
patient:
PHI:
Medical record number (MRN)
Non-PHI Demographic data
- Stockholm3 Identification number
- Race
- Zip code
Clinical data
- Total PSA
- Age on sampling date [years]
- Family history of prostate cancer
- Use of 5-alpha reductase inhibitors
- Earlier biopsy conducted
- Prostate volume [Prostate volume as measure with US]
- Digital rectal exam status [Benign/normal, Nodule/induration felt, Asymmetry, Not
performed]
AND
Outcome data - Results from biopsy performed immediately after blood venipuncture, i.e.:
Results will be separated into targeted biopsy cores and systematic biopsy cores
- Gleason Score 1
- Gleason Score 2
- Gleason Sum
- Cancer length (mm) (total and highest grade)
- Number of cores
- Number of positive cores
- Time to perform biopsy after blood draw [days]
- Results from MRI, i.e. Prostate Imaging Reporting & Data System (PIRADS) (0, 1, 2, 3, 4,
5)
Permitted use:
To run the Stockholm3 test defined by Gronberg et al AND Ancestry informative genetic markers
Samples will be shipped to the Uppsala based laboratory (A23 Laboratory) in Sweden for
analysis. Each patient will have two blood samples (plasma and whole blood) and will be
frozen at -20 Celsius. The blood samples will then be tested for quantitative levels of serum
protein levels and DNA will be extracted from white blood cells and will be tested for gene
and small nucleotide polymorphic (SNPs) germline mutations and variants .
Genotyping will be performed using custom genotyping assays. Plasma will be used for protein
analysis. Plasma protein analysis will be performed using a custom protein assays including
total and free PSA, human glandular kallikrein 2 (hK2), microseminoprotein-beta (MSMB), and
Macrophage inhibitory cytokine 1 (MIC-1). PSA will be tested with a commercial assay.
Based on the results from the plasma protein analysis, the genetic analysis and clinical
data, the Stockholm3 Risk Score will be calculated. The participants' samples will be treated
in accordance with the regulations of Sweden at the laboratory based in Uppsala, Sweden.
Results of the tests will not be shared with the patient, nor will the results change or
impact medical decisions.
Expected Risks/Benefits
Anticipated Risks:
As this is retrospective analysis of deidentified patient information as well as deidentified
biospecimens, there are few anticipated risks. A confidentiality breach as well as loss of
privacy are possible, however every effort will be made to minimize this risk.
Anticipated Benefits:
Participants will advance scientific and clinical knowledge. Participants will also receive a
small payment for the time and involvement in the study.
Data Collection and Management Procedures
This study will utilize REDCap (Research Electronic Data Capture), a software toolset and
workflow methodology for electronic collection and management of clinical and research data,
to collect and store data. The Karolinska Institute Information Technology (KI-IT) Department
will be used as a central location for data processing and management. REDCap is hosted by
KI-IT in the Biomedicum (Solnavägen 9, Solna, Sweden 17165)
Data Analysis
Data analysis will be performed by the PI, co-investigators and/or key research personnel.
Quality Control and Quality Assurance
Key research personnel will be responsible for ensuring all data collected adheres to the
protocol.
Data and Safety Monitoring
This study is minimal risk and all efforts will be made to ensure there are no
confidentiality breaches as well as no loss of privacy.
Statistical Considerations
Power analysis This study is being conducted among several sites and thus pooled analysis
will be performed. Based on the framework developed a two-sided alpha of 0.05, 250 men in
each ethnicity gives 80% power to detect 10 percentage points differences in sensitivity
and/or specificity of the Stockholm3 test across different ethnicities. Pooled data from
several sites will allow for comparison between non-Hispanic White, Africa/Black, Asian, and
Hispanic White men. Within each ethnicity group of 250 men, the same sample size gives a 90%
power for detecting differences in area under curve (AUC) between Stockholm3 and PSA for
detection of PC that are at least 10 percentage points (primary aim).
Goal accruement is 500 men within each race/ethnicity, interim analysis will be performed
when 250 men in each race/ethnicity is enrolled.
Data Analysis Descriptive univariate statistics will be used to compare groups. Binary
endpoints will be assessed with a logistic regression model. Statistical analysis will
involve logistic regression modeling, AUC calculation, calibration analyses and calculation
of basic performance characteristics (sensitivity, specificity and predictive values).
Regulatory Requirements
Informed Consent The participants indicate their consent to participate in the study by
signing informed consents for accessing medical records, conducting genetic research and
undergoing venipuncture for blood samples.
Subject Confidentiality Data used for this study will be stored in REDCaps and all data
transferred between institutions will remain deidentified throughout the study.
Unanticipated Problems Any unanticipated problems will be immediately reported to the
Site-specific ethical review board by designated research personnel.
Prospective Randomized Comparison of Robotic Versus Open Radical Cystectomy
PRIMARY OBJECTIVES:
I. To compare RRC to ORC in terms of the difference in European Organization for Research and
Treatment of Cancer (EORTC) Quality of Life Questionnaire Core (QLQC)30 quality of life
instrument assessed at baseline to day 30 after radical cystectomy (RC).
II. To compare RRC to ORC in terms of the 90-day high-grade complication rate (where high
grade is defined as Clavien-Dindo grade 3-5).
III. To compare the peri-operative cost of the RC procedure, as defined as from the day of
hospital admission to the day of hospital discharge.
SECONDARY OBJECTIVES:
I. To estimate the differences between RRC and ORC in terms of the following quality of life
outcomes: Narcotic requirements prior to RC, during hospital stay and on days 7, 14, 30, 6
weeks, and 3, 6, 9 and 12 months; Visual Analog Scale (VAS) pain score prior to RC and on
days 7, 14, 30, 6 weeks, and 3, 6, 9 and 12 months; the EORTC-QLQ-30 prior to RC and at 3, 6,
9, and 12 months; the bladder cancer index (BCI) at 30 days and 3, 6, 9, and 12 months; the
Sexual Health Inventory for Men (SHIM) prior to RC and at 3, 6, 9, and 12 months; the World
Health Organization (WHO) Quality of Life (QOL) questionnaire prior to RC and at 30 days and
3, 6, 9, and 12 months.
II. To estimate the differences between RRC and ORC in terms of the following surgical and
complication outcomes: all complications occurring intraoperatively, during postoperative
hospitalization and during the 90 days post cystectomy assessed at 7, 14, and 30 days; at 6
weeks and at 3 months-graded according to the Clavien-Dindo classification; all
complications, all grade 3+ complications, and all grade 4+ complications; time to oral
intake; estimated blood loss during surgery, number of transfusions on the day of surgery;
drop in hematocrit at 24 hours; lymph node yield; and positive surgical margin.
III. To estimate the differences between RRC and ORC in terms of the following cost-related
outcomes: operation room time; number of disposables used; pharmacy costs; length of hospital
stay; admission to intensive care unit (ICU) prior to discharge & length of stay in ICU;
number of hospital readmissions within 30 and 90 days (3 months); necessary tests/procedures
to treat complications during hospitalization and within 30 and 90 days.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients undergo RRC at day 0.
ARM II: Patients undergo ORC at day 0.
After completion of study treatment, patients are followed up at 7 days, 30 days, 6 weeks,
and at 3, 6, 9, and 12 months.
A Prospective Observational Cohort Study to Assess miRNA 371 for Outcome Prediction in Patients With Newly Diagnosed Germ Cell Tumors
PRIMARY OBJECTIVE:
I. To estimate the positive predictive value within each of the early stage testicular
seminoma and nonseminoma groups using plasma miRNA 371 expression at relapse to detect germ
cell malignancy.
SECONDARY OBJECTIVES:
I. To bank prospectively obtained serial liquid biospecimens for low and moderate risk of
relapse patients annotated by patient level clinical data.
II. To bank prospectively collected, clinically annotated specimens for high risk patients
and non-testicular primary patients in collaboration with Children's Oncology Group study
AGCT 1531.
OUTLINE:
Patients undergo collection of blood every 3-6 months for up to 3 years.
A Randomized Phase 2 Study of Atezolizumab With or Without Selinexor in Alveolar Soft Part Sarcoma (AXIOM)
PRIMARY OBJECTIVE:
I. Determine the overall response rate (by Response Evaluation Criteria in Solid Tumors
[RECIST] version [v]1.1) for selinexor in combination with atezolizumab in immune checkpoint
inhibitor (ICI)-naive patients with alveolar soft part sarcoma (ASPS).
SECONDARY OBJECTIVE:
I. Assess the number of activated CD8+ T cells infiltrating the tumor before and after
atezolizumab + selinexor combination treatment, and correlate treatment-induced changes with
clinical response.
EXPLORATORY OBJECTIVES:
I. Compare RECIST v 1.1 versus (vs) immune RECIST (iRECIST) in patients with ASPS on
atezolizumab + selinexor.
II. Examine changes in PD-1/PD-L1 expression in the tumor microenvironment before and after
atezolizumab + selinexor treatment, and correlate treatment-induced changes with clinical
response.
III. Evaluate potential associations between atezolizumab + selinexor activity and tumor
genomic alterations.
OUTLINE: This is a randomized phase 2 trial that incorporates a safety run-in of the
selinexor in combination with atexolizumab. After the safety run-in phase, patients are
randomized to 1 of 2 arms. Patients with advanced soft tissue sarcoma are assigned to Arm I.
ARM I: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 8 of cycle
1, and then on day 1 of subsequent cycles. Patients also receive selinexor orally (PO) once
weekly (QW) on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of
disease progression or unacceptable toxicity. Patients also undergo biopsy at baseline, cycle
1 day 8 and cycle 3 day 1, computed tomography (CT) and magnetic resonance imaging (MRI) at
baseline, end of cycle 2, and every 2 cycles thereafter, and collection of blood samples
throughout the study.
ARM II: Patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Cycles
repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients
with disease progression may crossover to Arm I. Patients also undergo biopsy at baseline and
cycle 3 day 1, CT and MRI at baseline, end of cycle 2, and every 2 cycles thereafter, and
collection of blood samples throughout the study.
After completion of study treatment, participants are followed up for 30 days.
An Open Label Multicentric Phase 1 Study of Oral PI3K/mTOR Inhibitor P7170 in Patients With Advanced Refractory Solid Tumors.
An open label multicentric Phase 1 study of oral PI3K/mTOR inhibitor P7170 in patients with
advanced refractory solid tumors.The study will follow an Accelerated Titration Design (ATD)
with 100% dose increments until significant toxicity as described below; followed by standard
dose titration with 40% dose increments. Dose and schedule (alternate dosing regimen eg. OD,
BID, intermittent) will be determined by the dose escalation outlined in the protocol and
considering pharmacokinetics of the study drug determined from earlier cohorts.
Not recruiting | Any Cancer Condition or Solid Tumor | Multisite
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