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.
Medtronic CoreValve® U.S. Expanded Use Study
The primary objective of the study is to evaluate the safety and effectiveness of the
Medtronic CoreValve® System (MCS) in a subset of subjects excluded from the U.S. Extreme
Risk Pivotal Trial population due to one or more additional co-morbidities, as measured by a
composite of all-cause death or major stroke at 12 months, in the treatment of symptomatic
severe aortic stenosis in subjects necessitating aortic valve replacement. Subjects enrolled
in this study have a predicted operative mortality or serious, irreversible morbidity risk
of ≥50% at 30 days associated with surgical aortic valve replacement.
Surveillance Monitoring for ART Toxicities Study in HIV Uninfected Children Born to HIV Infected Women
Many antiretroviral therapy (ART) medications given to a pregnant woman cross the placenta
and can be detected in the amniotic fluid and cord blood resulting in substantial fetal
exposure. Therefore, there is concern about toxicity of the drugs in the fetus and infant. It
is noteworthy that none of the currently approved ART medications for the prevention of
maternal to fetal transmission of HIV are in Food and Drug Administration (FDA) Pregnancy
Category A (no fetal risk ascertained in adequately controlled human studies). Thus, there is
continued need to examine the toxicity of ART in HIV transmission prevention for the
short-term toxicity of newer agents and combinations as well as the unanswered questions of
longer term toxicity and subtle adverse effects.
The study will use a registry approach to conduct active surveillance among children < 12
years of age at enrollment. Occurrences of abnormalities from ART exposure in utero and/or in
the first two months of life will be sought in multiple domains, including metabolic, growth,
cardiac, neurologic, neurodevelopmental, behavior, language, and hearing. Clinical and
laboratory data will be examined for abnormalities through a hierarchy of evaluations:
adverse events (AE) will be identified → selected AEs will trigger predefined additional
evaluations → significant observations will be defined as cases → a pattern of significant
study-wide cases will be defined as signals. The incidence of these events of interest will
be monitored over time and by ART regimen, and compared with historical data that may be
suggestive of a signal. Some signals may be testable using existing and/or previously
collected data, while other signals may indicate the need for additional hypothesis-driven
studies outside of SMARTT.
The objectives of SMARTT are:
1. To estimate the occurrence of potential ART-related toxicities through an ongoing
surveillance system among HIV-uninfected children born to mothers with HIV infection
with and without exposure to ART in utero and/or in the first two months of life and
compare the occurrences of these outcomes with other sources of data as well as by ART
exposures; and
2. To actively encourage hypothesis-driven studies to confirm that the signals are due to
ART exposure in utero and/or in the first two months of life. Note that the full design
and execution of these studies may be beyond the scope of the SMARTT study but will be
facilitated by SMARTT.
The specific aims of SMARTT are:
1. To create a Static Surveillance Cohort to extend domain-specific data collection in
children either 1) previously enrolled in any of the approved studies for enrollment
into SMARTT; 2) previously enrolled in another pediatric HIV/AIDS cohort study with
SMARTT Protocol Chair approval, or 3) not previously enrolled in an approved study but
with equivalent data available in the medical record;
2. To create a Dynamic Surveillance Cohort to examine domain-specific data of children
newly exposed to ART in utero and/or in the first two months of life;
3. To create a Young Adult Cohort to study long-term outcomes in SMARTT participants
formerly enrolled in the Static and Dynamic cohorts.
4. To identify a set of "triggers" for each domain that define a "signal" of possible ART
toxicity and compare the occurrence of these signals with previously collected data and
by ART exposure; and
5. To encourage and facilitate the development of hypothesis-driven studies to evaluate
whether a "signal" is the result of ART exposure in utero and/or in the first two months
of life.
A multicentre, multinational, randomised, parallel-group, placebo-controlled (double blind) and active-controlled (open) trial to compare the efficacy and safety of once weekly dosing of NNC0195-0092 with once weekly dosing of placebo and daily Norditropin FlexPro in adults with growth hormone deficiency for 35 weeks, followed by a 53-week open-label extension period
Rationale: The aim of the project is to develop a long-acting once-weekly GH product which is a safe and efficacious but has greater convenience and thus potentially better compliance compared to standard once daily GH treatment.
Intervention: Subjects will receive subcutaneous injection of study drug ( NNC0195-0092, Norditropin FlexPro or placebo. ) and being monitored efficacy and safety with AE, MRI, DEXA scan, Vital signs, Hts and weights, Hematology, Biochemistry, thyroid function, Hormones ,ECG and Eye exams.
Objectives or purpose: The primary objective is to access the efficacy and the secondary objective is to evaluate the clinical safety.
Study population or sample characteristics: This study is aiming for subjects who is between age of 23-79 with diagnosis of GHD who has no history of or active malignant disease.
Study methodology: Two hundred and eighty will be randomized in a 2:2:1 (NNC0195-0092: Norditropin FlexPro: placebo) ratio. The trial will compare the efficacy and safety of once weekly dosing of NNC0195-0092 with once weekly dosing of placebo and daily dosing of Norditropin FlexPro in adults with GHDs during the 35-week period (8 week dose titration, 26 week fixed dose treatment followed by 1 week washout), with a 53-week extension period (8 week dose titration, 44 week fixed dose treatment followed by 1 week washout). After the main trial period placebo subjects will be switched to NNC0195-0092 treatment and Norditropin FlexPro subjects will be randomised 1:1 to NNC0195-0092 or Norditropin FlexPro.
Study endpoints or outcomes: The primary endpoint will be at week 34 for the main trial and the secondary endpoint will be at 86 weeks for the extension period of trial. The study is looking for the outcome of changing in truncal fat mass and truncal lean body mass after the treatment, as well as to evaluate the safety of this drug.
Follow-up: Follow up visit will be scheduled 2 weeks after last treatment.
Statistics and plans for analysis: For each of the complete data sets, the change from baseline to 34 weeks is analysed using an ANCOVA model with treatment, GHD onset type, sex, region, DM and sex by region by DMinteraction as factors and the baseline truncal fat value as a covariate. From the pooled estimates, the treatment difference at Week 34 between NNC0195-0092 and placebo willbe estimated and the corresponding 95% CI and p-value will be calculated.Superiority of NNC0195-0092 over placebo will be considered confirmed if the upper boundary of
the two-sided 95% CI of the treatment difference (NNC0195-0092 placebo) is below 0. Sensitivity analysis will also be completed. Two partial database locks are planned during the trial.
Very Early Intensive Treatment of HIV-Infected Infants to Achieve HIV Remission: A Phase I/II Proof of Concept Study
The purpose of this study is to explore the effects of early intensive antiretroviral therapy
(ART) on achieving HIV remission (HIV RNA below the limit of detection of the assay) among
HIV-infected infants.
The study will enroll two cohorts. Cohort 1 will include infants at high risk for in utero
HIV infection. Cohort 2 will include in utero HIV-infected, ART-started infants.
Three early intensive therapy regimens will be assessed. Regimen 1L will include 2 nucleoside
reverse transcriptase inhibitors (NRTIs) plus nevirapine (NVP) plus lopinavir/ritonavir
(LPV/r). Regimen 2R will include 2 NRTIs plus NVP plus raltegravir (RAL). Regimen 2RV will
include 2 NRTIs plus NVP plus RAL plus VRC01 monoclonal antibody.
The study will be conducted in four steps. In Step 1, Cohort 1 infants will be enrolled for
evaluation of HIV infection and initiation of early intensive therapy within 48 hours of
birth. Infants in whom in utero HIV infection is excluded will switch from the study regimen
to standard perinatal prophylaxis per local guidelines within two weeks; these infants will
continue in Step 1 safety monitoring for two additional weeks, undergo final HIV testing at
approximately 12 weeks of age, and then exit the study. Infants in whom in utero HIV
infection is confirmed will enter Step 2 at least two weeks after enrollment in Step 1.
In Step 2, Cohort 1 infants identified with in utero HIV infection and Cohort 2 infants will
receive the study regimen for up to 288 weeks. Beginning at Step 2 Week 84, children who
achieved HIV RNA suppression by Week 24, and maintained suppression thereafter, with no HIV
RNA detected at or after Week 48, will be evaluated for possible treatment cessation.
In Step 3, children in Step 2 who meet criteria for treatment cessation will stop ART, and be
closely monitored for viral rebound for up to five years.
In Step 4, children who experience viral rebound in Step 3 or meet other Step 4 inclusion
criteria will re-initiate ART, and be closely monitored for viral re-suppression on ART until
five years of age or six months after re-suppression, whichever is later.
HIV-uninfected infants will be followed for 12 weeks. HIV-infected infants will be followed
for up to 288 weeks in Step 2 (on ART); those entering Step 3 will be followed for primary
endpoint ascertainment at 48 weeks and for up to a total of five years (off ART) in this
step.
A Phase 3, Randomized, Double Blind, Placebo And Active‑Controlled, Multicenter, Parallel‑Group Study Of The Analgesic Efficacy And Safety Of Tanezumab In Adult Subjects With Chronic Low Back Pain
This is a randomized, double blind, placebo and active controlled, multicenter, parallel
group Phase 3 study of the efficacy and safety of tanezumab when administered by SC
injection for up to 56 weeks in subjects with chronic low back pain. Approximately 1800
subjects will be randomized to 1 of 4 treatment groups in a 2:2:2:3 ratio (ie, 400 subjects
per treatment group for the placebo, tanezumab 5 mg and tanezumab 10 mg treatment groups and
600 subjects in the tramadol PR treatment group). Treatment groups will include: 1.) Placebo
administered SC at an 8 week interval plus placebo matching tramadol PR up to Week 16. At
the Week 16 visit, subjects in this group who meet the efficacy responder criteria will be
switched in a blinded fashion in a 1:1 ratio to either tanezumab 5 mg or tanezumab 10 mg
administered SC at an 8 week interval plus placebo matching tramadol PR to Week 56;
2.)Tanezumab 5 mg SC administered at an 8 week interval plus placebo matching tramadol PR to
Week 56; 3.) Tanezumab 10 mg SC administered at an 8 week interval plus placebo matching
tramadol PR to Week 56; 4.) Oral tramadol PR plus placebo administered SC at an 8 week
interval to Week 56. The study is designed with a total duration (post randomization) of up
to 80 weeks and will consist of three periods: Screening (up to a maximum of 37 days;
includes a Washout Period and an Initial Pain Assessment Period), a Double blind Treatment
Period (comprised of a 16 week Primary Efficacy Phase and a 40 week Long Term Safety and
Efficacy Phase), and a Follow up Period (24 weeks). The Screening Period (beginning up to 37
days prior to Randomization) includes a Washout Period (lasting 2 32 days), if required, and
an Initial Pain Assessment Period (the 5 days prior to Randomization/Baseline). Prior to
entering the study, subjects must have a documented history of previous inadequate treatment
response to medications in 3 different categories of agents commonly used to treat and
generally considered effective for the treatment of chronic low back pain.
Inspire Upper Airway Stimulation Post-FDA Approval Study
The purpose of this study is to obtain additional long-term safety and efficacy data on the use of the Inspire Upper Airway Stimulation System to treat obstructive sleep apnea.
Assessing the safety and efficacy of Macitentan in patients with portopulmonary hypertension
Several drugs (blood vessel dilators), including macitentan, are currently approved for the treatment of pulmonary arterial hypertension (PAH) in many parts of the world. These drugs have significantly improved the outcome of the condition. However, none of these treatments have been evaluated in portopulmonary hypertension, a form of PAH caused by liver disease. The purpose of this study is to assess the safety and effectiveness of macitentan in portopulmonary hypertension by looking at several clinical indicators, including the pressures within the arteries of the lungs and a person’s capacity for exercise.
Recruiting | High Blood Pressure / Hypertension | Not Multisite
An Open-Label, Phase 1/2A Dose Escalation Study of Safety and Efficacy of NEO100 in Recurrent or Progressive Grade III or Grade IV Gliomas With IDH1 Mutation
Perillyl alcohol has previously been tested in 15 clinical studies in > 600 subjects This
includes 13 studies in 255 subjects using oral administration sponsored by the National
Cancer Institute and two studies in > 350 subjects using intranasal administration in Brazil.
NEO100 is a highly purified (>99%) form of perillyl alcohol. Studies in Brazil suggest
improved survival for patients with recurrent glioblastoma. Doses of 96 mg qid, 144mg qid,
192mg qid, and 288 mg qid administered intranasally to patients with recurrent GBM for up to
6 months, disease progression or death. From 3 to 6 patients will be evaluated after first
cycle (28 days) until MTD is reached. MRI with gadolinium will be at base line, and at the
beginning of even cycles. A total of 25 patients will be treated at the MTD. PK studies will
be conducted during Phase 1 at first dosing, and after first dose of 3rd cycle.
A Placebo-controlled Study of a Targeted Immune Therapy Drug in Subjects with Moderate to Severe Ulcerative Colitis (UC)
The primary objective of this study is to study the effectiveness of a novel targeted immune therapy (biologic) called LY3074828 in treating moderate to severe ulcerative colitis. This study will take place over 120 weeks and all study visits and procedures will be provided at no cost to you. During the initial part of this study, patients will either receive LY3074828, or placebo ("dummy" treatment). Patients who receive placebo initially will have the opportunity to receive the study drug LY3074828 later in the study.
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