Using Light-Scattering Spectroscopy to detect advanced stage breast cancer
The purpose of this study is to determine the safety and effectiveness of an investigational device for the detection of breast cancer. The device is an optical probe that uses a technique called light scattering spectroscopy (LSS). LSS uses visible light reflected from the breast to provide information about the presence of cancer. When the probe lightly touches the nipple, it shines the light into the breast and collects the light that is reflected back. The results of the evaluation with the LSS probe will be compared to the results of routine tests such as mammograms, and the findings will decide if this device may be useful in detecting breast cancer.
Abiraterone Acetate Treatment for Prostate Cancer Patients With a PSA of More Than Four Following Initial Androgen Deprivation Therapy Phase II
OBJECTIVES:
Primary
- To assess the rate of achieving a prostate-specific antigen (PSA) of ≤ 0.2 ng/mL with
abiraterone acetate therapy in men with metastatic prostate cancer with a sub-optimal
response to androgen-deprivation therapy (ADT).
Secondary
- To assess the overall survival and objective progression-free survival of this group of
patients.
- To assess PSA partial response.
- To evaluate the qualitative and quantitative toxicity of abiraterone acetate.
OUTLINE: This is a multicenter study.
Patients receive abiraterone acetate orally daily on days 1-28. Courses repeat every 28 days
in the absence of disease progression or unacceptable toxicity.
Patients receive androgen blockade with GNRH agonist (goserelin acetate or leuprolide
acetate) or a GNRH antagonist (degarelix) per the treating physician and this will be given
continuously until evidence of disease progression. Bilateral surgical orchiectomy is also
acceptable.
After completion of study therapy, patients are followed up every 3 months for 1 year and
then every 6 months for up to 3 years.
Randomized, Phase II Study of Pembrolizumab (MK-3475) Versus Chemotherapy in Patients With Advanced Melanoma (KEYNOTE 002)
Two interim and one final statistical analyses were planned for and conducted during this
study:
- Interim Analysis 1 (futility analysis),
- Interim Analysis 2 (~18 months into study): database cutoff date 12-May-2014, and
- Final Analysis (~36 months into study): database cutoff date 16-Nov-2015. The End of
Trial Analysis for the study was conducted at ~75 months into the study: database cutoff
date 31-Jan-2019.
Phase I/II Study of High Dose Interleukin 2, Aldesleukin, in Combination With the Histone Deacetylase Inhibitor Entinostat in Patients With Metastatic Renal Cell Carcinoma
PRIMARY OBJECTIVES:
I. To evaluate the safety and tolerability of high dose interleukin 2 (aldesleukin) in
combination with entinostat in patients with metastatic renal cell carcinoma (RCC). (Phase
I) II. To monitor toxicity and estimate the efficacy of high dose aldesleukin combined with
entinostat in patients with metastatic RCC. (Phase II)
SECONDARY OBJECTIVES:
I. To compare the time-to-tumor progression, progression-free survival and overall survival
of patients with metastatic RCC treated with high dose aldesleukin combined with entinostat
to the historical data of patients treated with high dose aldesleukin alone. (Phase II) II.
To assess the toxicity of high dose aldesleukin combined with entinostat. (Phase II) III. To
evaluate entinostat pharmacodynamics (PD) in blood and tumor samples. (Phase II) IV. To
measure the association between baseline laboratory parameters (e.g. cluster of
differentiation [CD]4+, CD8+, CD4+/forkhead box P3 [Foxp3]), tumor blood metabolism, and a
variety of response variables (e.g. toxicity, response and survival). (Phase II) V. To
explore the relationship between entinostat exposure with PD endpoints (e.g. toxicity and
histone acetylation in peripheral blood mononuclear cells or peripheral blood mononuclear
cells [PBMNCs] and changes in T cell subset population). (Phase II) VI. To evaluate the
modulation of tumor metabolism by fluorodeoxyglucose (FDG, fludeoxyglucose F 18) positron
emission tomography (PET)/computed tomography (CT) scan. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of entinostat followed by a phase II
study.
Patients receive entinostat orally (PO) every 2 weeks beginning on day -14 and high-dose
aldesleukin intravenously (IV) every 8 hours on days 1-5 and 15-19. Courses repeat every 84
days* in the absence of disease progression or unacceptable toxicity.
NOTE: *Patients with evidence of tumor shrinkage may receive up to 3 courses of high-dose
aldesleukin therapy. Patients with stable disease by Response Evaluation Criteria in Solid
Tumors (RECIST) version 1.0 criteria, but without evidence of tumor shrinkage after two
courses will receive only entinostat until disease progression is documented.
After completion of study treatment, patients are followed up at 30 days and then every 3
months thereafter.
A Prospective, Longitudinal, Observational Study in Newly Diagnosed Multiple Myeloma (MM) Patients to Assess the Relationship Between Patient Outcomes, Treatment Regimens and Molecular Profiles
Understanding the molecular basis of cancer is a critical step toward devising the most
effective treatment of the patient as an individual. The promise of molecular targeted
therapeutics and personalized cancer care has been demonstrated in breast and lung cancer and
chronic myeloid leukemia. However, similar examples of success in multiple myeloma have not
been achieved despite extensive basic research as well as clinical advances. What is well
understood is that myeloma is a heterogeneous disease with great genetic and epigenetic
complexity.22, 23 Therefore, there remains a critical need to understand myeloma patient
biology in the context of current patient care.24 The objective of this longitudinal study is
to identify patient subgroups and phenotypes defined by molecular profiling and clinical
features. These profiles will enable a better understanding of mechanisms of disease, drug
response and patient relapse. Ultimately the study is intended to drive successful drug
development and patient care in multiple myeloma.
A Phase I/Randomized Phase II Study of Cediranib (NSC#732208) Versus Placebo in Combination With Cisplatin and Pemetrexed in Chemonaive Patients With Malignant Pleural Mesothelioma
PRIMARY OBJECTIVES:
I. To establish the maximum tolerated dose (MTD) and the recommended phase II dose of
cediranib maleate (cediranib) in combination with cisplatin and pemetrexed disodium
(pemetrexed). (Phase I) II. To assess the safety and toxicity of the regimen. (Phase I) III.
To assess whether cisplatin/pemetrexed plus cediranib as compared to cisplatin/pemetrexed
plus placebo improves progression-free survival in patients with malignant pleural
mesothelioma. (Phase II) IV. To compare overall survival in patients treated with
cisplatin/pemetrexed plus cediranib to those treated with cisplatin/pemetrexed plus placebo.
(Phase II) V. To assess the safety and toxicity profile of the regimen. (Phase II) VI. To
assess response rate (confirmed and unconfirmed, complete and partial responses) and disease
control rate (response or stable disease) in the subset of patients with measurable disease
by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. (Phase II) VII. To assess
response rate and disease control rate using modified RECIST criteria for pleural tumors in
the subset of patients with measurable disease by modified RECIST criteria for pleural
tumors. (Phase II) VIII. To assess the rate of agreement between local and central pathology
review of mesothelioma and its histologic subtypes. (Phase II) IX. To collect specimens for
banking for use in future research studies. (Phase II)
OUTLINE: This is a phase I dose-escalation study of cediranib maleate followed by a phase II
study.
PHASE I (CLOSED): Patients receive pemetrexed disodium intravenously (IV) over 10 minutes and
cisplatin IV over 2 hours on day 1 and cediranib maleate orally (PO) once daily (QD) on days
1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or
unacceptable toxicity. Patients then receive cediranib maleate alone PO QD in the absence of
disease progression or unacceptable toxicity.
PHASE II: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours
on day 1 and cediranib maleate PO QD on days 1-21. Treatment repeats every 21 days for 6
courses in the absence of disease progression or unacceptable toxicity. Patients then receive
cediranib maleate alone PO QD in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive pemetrexed disodium and cisplatin as in arm I and placebo PO QD on
days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease
progression or unacceptable toxicity. Patients then receive placebo alone PO QD in the
absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 2 years and
then at 3 years.
Brain Amyloid Imaging With Pittsburgh Compound B in Normal Aging, Mild Cognitive Impairment, and Dementia
Identification of risk factors and biomarkers of neurodegenerative disease is essential in
caring for the growing numbers of elderly. Imaging biomarkers provide non-invasive ways to
look at brain function. A new PET imaging agent, Pittsburgh Compound B (PiB), that identifies
brain amyloid is an exciting development in brain imaging that needs to be studied. We plan
to study this imaging technique in normal volunteers and patients with a variety of
neurodegenerative diseases to determine its utility. Long term followup of these subjects
will allow us to understand the predictive ability of this new test.
Phytoserms for menopause symptoms and age associated memory decline
Background and rationale:Selective estrogen receptor (ER) targeting may be a novel therapeutic target for the development of therapies for a range of conditions including cognitive impairment and age-related ovarian failure (menopause). There are plausible mechanisms by which ER receptor stimulation could lead to improved cognition, feelings of well being, reduced risks for cognitive impairment and improved vasomotor symptoms.A formulation composed of rationally-selected ER-selective phytoestrogens (phytoSERMs) was developed that provides a greater effect than the various food supplements ("nutraceuticals") that are mixtures with both ER and ER selective components. This formulation is composed of content that includes synergistic rather than antagonistic effects on estrogen receptors and could likely generate salutary therapeutic effects. The formulation enhances ER responses by adding equol to genistein and daidzein in equal amounts moderating potencial influences of inter-individual differences in the production of equol. Advantages of the formulation are: (1) reduction of antagonistic interactions that occur in complex soy-derived isoflavone preparations; and (2) minimization of adverse effects associated with ER activation in reproductive tissues. Thus, it may serve as an alternative to current over-the-counter therapies.Primary objectives and pupose:To examine in a randomized, placebo-controlled trial of 12 weeks duration evidence for safety, improved cognitive performance and vasomotor symptoms for a specific phytoSERM formulation Secondary objectives:1. To assess single-dose pharmacokinetics of the three constituents of phytoSERM combination over 24 hours in a subset of 18 participants randomly assigned 100 mg, 50 mg, or placebo tablets.2. To assess safety, tolerability of a 100 mg and 50 mg daily dose compared to placebo over 4 weeks3. To assess potential efficacy indicators of phytoSERM combination on cognitive performance and vasomotor symptoms by means of a 4-week treatment, 2 period, placebo-controlled crossover design for a subset of participants4. To develop biomarkers for response (i.e., for peripheral lipid peroxidation and mitochondrial function)Study design:Two stage, dose-range, double-blinded, parallel-group, placebo-controlled adaptive design 12 week treatment duration trial; with an embedded 2-period, 4-week treatment, crossover design for a subset of participants; and an embedded single-dose, 24 hour, pharmacokinetic study for a subset of participants. Allocation ratio will initially be 1:1:1, 100 mg, 50 mg, and placebo dose for the first 36 participants, with a possible change in allocation based on the adaptation (see protocol)Study endpoints:Adverse events over the first 4 weeks, and over 12 weeks;Cognitive performance on a 6-test battery, vasomotor symptoms, and behavioral symptoms at 4, 8, and 12 weeks.Blood levels of the three constituents of phytoSERM combination over 24 hours in the subset in the pharmacokinetic study; and blood levels at 4, 8 and 12 weeks for all participantsBlood for biomarker development at baseline, 4, 8, and 12 weeksEligibility criteria:Generally healthy, peri to postmenopausal women, ages 45 to 60, intact uteri and ovaries, last natural menstrual cycle completed from 60 days to less than 4 years prior to screening, having at least 1 cognitive complaint and 1 vasomotor-related symptom per day (on the Memory Assessment Questionnaire and Greene Climacteric Scale). Intervention:Oral tablets consisting of equal parts genestein, daidzein, and S-equol) totaling 100 mg per tablet and 50 mg per tablet; and mathching placeboProcedures and data collection: At baseline, physical exam, neuropsychological tests, vasomotor symptoms and mood scales;In person visits for screening, baseline, weeks 4, 8, and 12 during which medication effects will be assessed, cognitive and behavioral tests performed, and blood for plasma levels and biomarkers obtained; Telephone contacts at weeks 1, 2, 6, and 10; An in-person visit or telephone contact at 16 weeks (4 weeks after discontinuation); Blood samples for drug levels and pharmacokinetics during the first 24 hours for the subset participating;Blood at baseline, weeks 4, 8, and 12 for drug levels and biomarker development for the whole sampleStatistical considerations:Two-stage adaptive design. Analysis of first stage at 4 weeks after 36 participants are randomized and followed: Primary analysis will use Generalized Estimating Equation (GEE) methods to assess group differences in the outcomes in a modified intent-to-treat sample (i.e., randomized, took at least one dose, and had at least one follow-up with outcomes measures. Observed cases (at least 80% compliant and completed all outcomes) will be assessed in secondary analyses
A Randomized Phase II Pilot Study Prospectively Evaluating Treatment for Patients Based on ERCC1(Excision Repair Cross-Complementing 1) for Advanced/Metastatic Esophageal, Gastric or Gastroesophageal Junction (GEJ) Cancer
OBJECTIVES:
- To assess progression-free survival of high-excision repair cross-complementing 1(ERCC1)
patients with advanced or metastatic cancer of the esophagus, stomach, or
gastroesophageal junction (GEJ) treated with FOLFOX comprising oxaliplatin, leucovorin
calcium, and fluorouracil compared to those treated with irinotecan hydrochloride plus
docetaxel.
- To assess progression-free survival of low-ERCC1 patients with advanced or metastatic
cancer of the esophagus, stomach, or GEJ treated with FOLFOX compared to those treated
with irinotecan hydrochloride plus docetaxel.
- To assess progression-free survival of low-ERCC1 patients with advanced or metastatic
cancer of the esophagus, stomach, or GEJ treated with FOLFOX compared to high-ERCC1
patients treated with FOLFOX.
- To assess overall survival of and toxicities in each of the two treatment arms in this
group of patients.
- To assess the response probability (confirmed and unconfirmed, complete and partial
responses) in the subset of patients with measurable disease in each of the two
treatment arms.
- To explore whether there is evidence of interaction between treatment arm and ERCC1
expression in this group of patients. (Exploratory)
- To bank tissue and blood for future translational medicine studies; a) To explore the
relationship of ERCC-1 and ERCC-2 single nucleotide polymorphism (SNP) genotypes with
clinical outcome in these patients; and b) To explore the association between germline
variations in these SNPs and ERCC-1 mRNA expression in these patients. (Exploratory)
OUTLINE: This is a multicenter study. Patients are stratified according to ERCC1 expression
(high [≥ 1.7] vs low [< 1.7]), and disease site (esophageal vs gastric/gastroesophageal
junction). Patients are randomized to 1 of 2 treatment arms.
- Arm I (FOLFOX): Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV
over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-2. Courses repeat
every 14 days in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive irinotecan hydrochloride IV over 90 minutes and docetaxel IV
over 30-60 minutes on days 1 and 8. Courses repeat every 21 days in the absence of
disease progression or unacceptable toxicity.
Blood and tumor tissue samples may be collected for ERCC1 expression analysis and future
research studies.
After completion of study treatment, patients are followed up every 3 months for up to 3
years.
The Role of Tonsillectomy in Adults With Marked Tonsillar Hypertrophy and Obstructive Sleep Apnea
Purpose: To determine if tonsillectomy eliminates symptoms of obstructive sleep apnea in
patients with obstructive sleep apnea and marked tonsillar hypertrophy with normal soft
palate and uvula length.
Specific Aims: 1. To determine if tonsillectomy eliminates obstructive sleep apnea as
determined by polysomnography. 2. To determine if tonsillectomy eliminates excessive daytime
sleepiness and other obstructive sleep apnea symptoms.
Rationale: Current surgical procedures for obstructive sleep apnea include tonsillectomy with
soft palate surgery (including uvulopalatopharyngoplasty). Tonsillectomy alone may provide
sufficient benefit in adults with marked tonsillar hypertrophy and normal soft palate and
uvula length, avoiding the need for additional soft palate surgery.
Intervention: Tonsillectomy will be performed as standard of care, in patients who would be
undergoing said surgery regardless of study. Study intervention includes multiple home sleep
studies to determine effect of tonsillectomy in impacting symptoms of sleep apnea.
Study Population: Inclusion criteria: Subjects must be at least 18 years old, have documented
obstructive sleep apnea; be willing to undergo 3 home sleep studies; and have markedly
hypertrophic (3+ or 4+) tonsils. Exclusion criteria: Subjects must not have any craniofacial
abnormality; normal soft palate length (<4 cm) and uvula length ((<2 cm); must have no
history of chronic obstructive pulmonary disease, untreated psychological disorder, restless
leg syndrome, alcohol or drug abuse; must have a body mass index <35; must not plan to use
continuous positive airway pressure during the study period, and lack significant nasal
obstruction. The subjects will serve as their own control.
Methods and Follow Up: This two-center prospective study will include evaluation of
demographics, clinical symptoms, extent of tonsillar hypertrophy, sleep habits, and home
sleep studies. All subjects will undergo a 4-8 week period of watchful waiting (standard
minimum delay for scheduling surgery), followed by tonsillectomy alone, with values at
baseline compared to a period of watchful waiting and post-tonsillectomy.
Outcomes: Primary outcome is apnea-hypopnea index (from home sleep study). Exploratory
outcomes include other sleep study results and subjective assessments (sleep-related quality
of life with the Functional Outcome of Sleep Questionnaire and daytime sleepiness with the
Epworth Sleepiness Scale).
Statistics and Plans for Analysis: The minimum sample size is 44 subjects, with an enrollment
target of 60 subjects that will accommodate a 25% dropout rate. Standard statistical tests
(e.g., paired t-tests for continuous measures) will evaluate potential differences between
outcome measures at baseline vs. post-watchful waiting and baseline vs. post-tonsillectomy.
Similarly, standard and appropriate statistical tests (e.g, t-tests for continuous measures)
will compare changes with watchful waiting vs. tonsillectomy (e.g., baseline vs.
post-watchful against baseline vs. post-tonsillectomy).
A Phase I Study of ARQ 197 in Combination With IV Topotecan in Advanced Solid Tumors With an Expansion Cohort in Small Cell Lung Cancer
PRIMARY OBJECTIVES:
I. To establish the recommended phase 2 dose (RP2D) for the combination of ARQ 197
(tivantinib) and intravenous (IV) topotecan (topotecan hydrochloride).
II. To describe the toxicities of ARQ 197 and IV topotecan at each dose studied.
III. To characterize the pharmacokinetic behavior of ARQ 197 given concurrent use of IV
topotecan.
IV. To document all clinical responses to ARQ 197 with IV topotecan.
OUTLINE: This is a dose-escalation study of tivantinib and topotecan hydrochloride.
Patients receive tivantinib orally (PO) twice daily (BID) on days 1-21, topotecan
hydrochloride IV over 30 minutes on days 1-5, and pegfilgrastim subcutaneously (SC) on day 6.
Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 4 weeks.
Amyloid Imaging and Cognitive Impairment After Intracerebral Hemorrhage
Cerebral Amyloid Angiopathy (CAA) and hypertension related hemorrhage are the main causes of
non traumatic primary intracerebral hemorrhage. In vivo diagnosis of these two cerebral
diseases may be difficult and is based on hematoma location and pattern of cerebral
microbleeds (CMB) distribution. We aimed to evaluate a multimodal approach including brain
MRI, Pet AV-45 Amyloid imaging and neuropsychological assessment to improve etiological
diagnosis of primary intracerebral hemorrhage. 70 patients with acute primary non traumatic
intracerebral hemorrhage will be prospectively included and two groups will be compared:
lobar hemorrhage group and deep hemorrhage group. Brain MRI, Pet AV-45 Cerebral Amyloid
imaging (during the first month) and neuropsychological assessment (Three months later) are
performed. Differences between the two groups are evaluated for AV45 cortical binding, CMB
distribution, White Matter Lesions and cognitive profile.
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