Repeatability Assessment of Quantitative DCE-MRI and DWI: A Multicenter Study of Functional Imaging Standardization in the Prostate
OBJECTIVES:
Primary
- Determine the test-retest performance, assessed by the repeatability coefficient [RC] of
K^trans and gadolinium curve (IAUGC90^bn) and measured by median pixel values of the
whole prostate.
- Determine the test-retest performance, assessed by the RC of diffusion-weighted imaging
(DWI) metrics D(t) and measured by median pixel values of the whole prostate.
Secondary
- Determine the test-retest performance, assessed by RC of K^trans, IAUGC90^bn, and D(t),
and measured by median pixel values of the dominant prostate tumor.
- Determine the effect of reader on the RC of dynamic contrast-enhanced magnetic resonance
imaging (DCE-MRI) and DWI metrics for whole prostate and tumor nodule target lesion.
- Determine whether T1-dependent or T1-independent methods for gadolinium quantification
in DCE-MRI studies produce differing values for the RC for K^trans and IAUGC90^bn.
- Explore the correlation between DCE-MRI and DWI metrics for both whole prostate and
dominant tumor nodule as target lesions. (Exploratory)
- Determine whether the "coffee break" approach toward test-retest analysis of
quantitative DWI provides a reasonable estimate of the RC of D(t)of the whole prostate,
using as the gold standard the RC of D(t) obtained between the two separate MRI visits.
(Exploratory)
OUTLINE: This is a multicenter study. Patients are stratified according to MRI vendor used
(Siemens vs GE vs Philips).
Patients receive gadolinium-based contrast IV and undergo DCE-MRI* and DWI 2 imaging at 2-14
days apart prior to treatment initiation. A central reader evaluation of the 2 successive
scans is then conducted.
NOTE: *At the discretion of the participating sites, the initial MRI visit (MRI SCAN 1) may
be supplemented with endorectal-coil imaging per institutional norms.
A Randomized Phase 2 Study of MK-2206 in Comparison With Everolimus in Refractory Renal Cell Carcinoma
PRIMARY OBJECTIVES:
I. To assess progression free survival (PFS) of vascular endothelial growth factor (VEGF)
therapy refractory renal cell carcinoma (RCC) patients who receive either MK-2206 (Akt
inhibitor MK-2206) or everolimus.
II. To assess safety of MK-2206 in patients with VEGF therapy refractory RCC.
SECONDARY OBJECTIVES:
I. To assess overall response rate (ORR) and overall survival (OS). (Clinical) II. To assess
time to treatment failure (TTF). (Clinical) III. To determine whether baseline AKT activation
is predictive for clinical benefit after treatment with MK-2206 or everolimus.
(Pre-clinical/exploratory) IV. To determine whether circulating cytokines and angiogenic
factors predict for clinical benefit after treatment with MK-2206 or everolimus.
(Pre-clinical/exploratory) V. To assess impact of karyotype on outcome in patients treated
with MK-2206 or everolimus. (Pre-clinical/exploratory)
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive Akt inhibitor MK2206 orally (PO) on days 1, 8, 15, and 22. Courses
repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients
who are progression free after 1 year may receive a 12 week study drug supply of Akt
inhibitor MK2206.
ARM II: Patients receive everolimus PO once daily (QD) on days 1-28. Courses repeat every 4
weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months.
A Pilot Study to Evaluate the Efficacy of Fosaprepitant and Granisetron Transdermal System for the Prevention of Acute and Delayed Nausea and Vomiting in Breast Cancer Patients and to Identify Predictors of Response
PRIMARY OBJECTIVE:
I. To evaluate the efficacy of the combination of fosaprepitant (fosaprepitant dimeglumine)
and granisetron transdermal system in the prevention of acute and delayed chemotherapy
induced nausea and vomiting in breast cancer patients undergoing adjuvant or neoadjuvant
chemotherapy.
SECONDARY OBJECTIVE:
I. To evaluate the safety of the combination of fosaprepitant and granisetron transdermal
system in breast cancer patients undergoing adjuvan or neoadjuvant chemotherapy.
EXPLORATORY OBJECTIVE:
I. To explore the use of single nucleotide polymorphisms (SNPs) in the 5âhydroxytryptamine-3
(5HT3) and neurokinin-1 (NK-1) receptors as potential markers of efficacy.
OUTLINE: Patients receive granisetron transdermal system patch 24-48 hrs before the
initiation of chemotherapy. Patients wear the granisetron transdermal system patch for 7
days. Patients receive fosaprepitant dimeglumine intravenously (IV) over 15 minutes on day 1
of chemotherapy. Treatment repeats every 2 or 3 weeks for up to 4 courses in the absence of
unacceptable toxicity.
A Randomized Phase III Trial Comparing Axillary Lymph Node Dissection to Axillary Radiation in Breast Cancer Patients (cT1-3 N1) Who Have Positive Sentinel Lymph Node Disease After Neoadjuvant Chemotherapy
PRIMARY OBJECTIVE:
I. To evaluate whether radiation to the undissected axilla and regional lymph nodes is not
inferior to axillary lymph node dissection with radiation to the regional lymph nodes but not
to the dissected axilla in terms of invasive breast cancer recurrence-free interval in
patients with positive sentinel lymph node(s) (SLN[s]) after completion of neoadjuvant
chemotherapy.
SECONDARY OBJECTIVES:
I. To evaluate whether radiation to the undissected axilla and regional lymph nodes is not
inferior to axillary lymph node dissection with radiation to the regional lymph nodes but not
to the dissected axilla in terms of the incidence of invasive loco-regional recurrences in
patients with a positive SLN(s) after completion of neoadjuvant chemotherapy.
II. To obtain an estimate of the distribution of residual disease burden scores.
III. To estimate the distribution of overall survival.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients undergo axillary lymph node dissection. Beginning 3-12 weeks following
surgery, patients undergo nodal radiation therapy comprising 3-dimensional (3D) conformal
radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), or proton radiation
therapy (PRT) 5 days a week for 5-6 weeks.
ARM II: Patients undergo axillary and nodal radiation therapy comprising 3D-CRT, IMRT, or PRT
5 days a week for 5-6 weeks.
After completion of study treatment, patients are followed up at least every 6 months for 2
years and then annually for 3 years.
A Phase 2 Evaluation of TRC105 in the Treatment of Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma
Angiogenesis plays a central role in the progression of epithelial ovarian cancer. In mouse
models, VEGF-inhibitors diminish ovarian tumor growth, metastasis and malignant ascites
formation. Independent Phase 2 trials have demonstrated single-agent activity for bevacizumab
in recurrent ovarian cancer, and randomized controlled Phase 3 trials are ongoing in the
first-line setting (GOG 0218 and ICON-7) and for recurrent disease (GOG 0213, OCEANS).
TRC105 is an antibody to CD105, an important non-VEGF angiogenic target on vascular
endothelial cells. TRC105 inhibits angiogenesis, tumor growth and metastases in preclinical
models. In a Phase 1 study of advanced solid tumors, TRC105 therapy caused a global reduction
in angiogenic biomarkers and reduced tumor burden at doses that were well-tolerated. We
hypothesize that TRC105 will have single-agent activity in recurrent ovarian cancer. By
targeting a non-VEGF pathway, TRC105 has the potential to complement VEGF inhibitors which
could represent a major advance in ovarian cancer therapy.
Effect of Corneal Preservation Time on Long-Term Graft Success
When the donor cornea is removed from the person who died, it is prepared for
transplantation by an eye bank. The donor cornea is placed into a liquid that helps
preserve the cornea until it is transplanted. The Food and Drug Administration (FDA) has
approved storage of the cornea in this liquid for up to 14 days before the transplant. The
purpose of this study is to see if the length of time the donor cornea is kept in the
preservation liquid before the transplant affects the likelihood of the transplant being
successful. We will follow participants for 3 years after transplant to see if there are any
differences in transplant success or in the number of transplanted endothelial cells (the
layer of cells that line the undersurface of the cornea) on the corneas that were preserved
for 7 days or less compared to those preserved between 8 and 14 days. We have no reason to
believe that there is any greater risk for transplant failure with either preservation time
group.
EVEREST: EVErolimus for Renal Cancer Ensuing Surgical Therapy, A Phase III Study
OBJECTIVES:
Primary
- to compare recurrence-free survival in renal carcinoma patients randomly assigned to 54
weeks of everolimus versus 54 weeks of placebo after nephrectomy or partial nephrectomy.
Secondary
- To compare the overall survival of patients treated with everolimus vs placebo.
- To compare qualitative and quantitative toxicity between the two study arms.
- To bank tissue and biologic specimens for future study of molecular biomarkers relevant
to the AKT/mTOR and other pathways implicated in the pathogenesis of renal carcinoma and
to investigate their potential predictive and prognostic value.
- To bank blood specimens for the future study of the relationship between steady-state
trough levels of everolimus and relevant side effects (lymphopenia, infection,
hyperglycemia, hypercholesterolemia, hypertriglyceridemia) in patients treated on this
study with everolimus.
OUTLINE: This is a multicenter study.
Patients are stratified according to pathologic stage (intermediate high-risk vs very
high-risk), histologic subtype (clear cell vs non-clear cell), and performance status (0 vs
1). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral everolimus once daily on days 1-42. Treatment repeats every
6 weeks for 9 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive oral placebo once daily on days 1-42. Treatment repeats every 6
weeks for 9 courses in the absence of disease progression or unacceptable toxicity.
Archived tumor tissue, plasma, and whole blood samples may be collected periodically for
biomarker analysis and other translational studies.
After completion of study treatment, patients are followed up every 6 months for 2 years and
then annually for 8 years.
A Phase III Trial of Accelerated Whole Breast Irradiation With Hypofractionation Plus Concurrent Boost Versus Standard Whole Breast Irradiation Plus Sequential Boost for Early-Stage Breast Cancer
OBJECTIVES:
Primary
- To determine whether an accelerated course of hypofractionated whole-breast irradiation
(WBI) including a concomitant boost to the tumor bed in 15 fractions following
lumpectomy will prove to be non-inferior in local control to a regimen of standard WBI
with a sequential boost following lumpectomy for early-stage breast cancer patients.
Secondary
- To determine whether breast-related symptoms and cosmesis from accelerated WBI that is
hypofractionated (in only 3 weeks) with a concomitant boost is non-inferior to standard
WBI with sequential boost.
- To determine whether the risk of late cardiac toxicity in patients with left-sided
breast cancer treated with hypofractionation will be non-inferior to conventional
fractionated radiation therapy (RT) based upon analysis of radiation dosimetry from
CT-based treatment planning and normal tissue complication probability (NTCP)
calculations.
- To determine whether CT-based conformal methods intensity-modulated radiation therapy
(IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for WBI are feasible in a
multi-institutional setting following lumpectomy in early-stage breast cancer patients
and whether dose-volume analyses can be established to assess treatment adequacy and
likelihood of toxicity.
- To determine that cosmetic results and breast-related symptoms 3 years after
hypofractionated breast radiation with concomitant boost will not be inferior to that
obtained 3 years after WBI with sequential boost.
- To determine whether future correlative studies can identify individual gene expressions
and biological host factors associated with toxicity and/or local recurrence from
standard and hypofractionated WBI.
- If shown to be non-inferior, to then determine if accelerated course of hypofractionated
WBI including a concomitant boost to the tumor bed in 15 fractions following lumpectomy
will prove to be superior in local control to a regimen of standard WBI with a
sequential boost following lumpectomy for early-stage breast cancer patients.
- To determine whether treatment costs for hypofractionated WBI with concomitant boost are
not higher than WBI with sequential boost.
OUTLINE: This is a multicenter study. Patients are stratified according to age (< 50 vs. ≥ 50
years), prior chemotherapy (yes vs. no), estrogen-receptor status (+ vs. -), and histology
grade (1-2 vs. 3). Patients are randomized to 1 of 2 treatment arms. Treatment begins within
9 weeks of last surgery or chemotherapy delivery.
After completion of study therapy, patients are followed at 1 month, at 6 months, and then
yearly.
A Multi-Center, Parallel-Group, Randomized, Double Blind, Adaptive Study Investigating the Safety and Efficacy of THR-184 in Patients at Increased Risk of Developing Cardiac Surgery Associated-Acute Kidney Injury (CSA-AKI)
The study has been designed to include patients scheduled for cardiac surgery who are
considered at increased risk for developing CSA-AKI. The eligibility criteria are intended to
enrich the study population with such patients.
Stage 1 consisted of 140 patients randomized in a 1:1:1:1 ratio (approximately 35 patients
per treatment arm) to Placebo or to one of three (3) THR-184 dose arms:
- initial pre-surgery low dose of THR-184 by three (3) post-surgery doses at the low dose,
or
- initial pre-surgery middle dose of THR-184 followed by three (3) post-surgery doses at
the low dose, or
- initial pre-surgery high dose of THR-184 followed by three (3) post-surgery doses at the
low dose
An interim analysis (IA) was performed by the Independent Statistical Center (ISC) and
presented to the Independent Data Monitoring Committee (IDMC). The IDMC indicated no safety
concerns and recommended that the study continue with the placebo arm and the initial
pre-surgery high dose arm. Additionally, another dosing arm will be added, which will
increase the dose post-surgery.
Stage 2 will consist of approximately 270 patients randomized in a 1:1:2 ratio to Placebo or
to a dose selected from one of the two (2) THR-184 dose arms:
- initial pre-surgery high dose of THR-184, followed by (3) post-surgery doses at the
original low dose;
- initial pre-surgery high dose of THR-184, followed by (3) post-surgery doses at ~80% of
the pre-surgery dose
Study treatment (THR-184 or placebo) will consist of one 60-minute IV infusion administered
prior to surgery, followed by a 60-minute IV infusion administered, beginning in the early
post-operative period, and followed by two (2) additional 60-minute IV infusions
administered, on consecutive days post-cardiac surgery.
The primary endpoint for the evaluation of efficacy in patients receiving THR-184, as
compared to patients receiving Placebo, will be the proportion of patients developing CSA-AKI
as measured by the Kidney Disease Improving Global Outcomes (KDIGO) criteria, as follows:
- Increase in Serum creatinine (SCr) by ≥0.3 mg/dl (>26.5 µmol/l) within 48 hours
post-surgery; or
- Increase in SCr to ≥1.5 times a baseline which has been measured in the previous 7 days;
or
- Urine volume <0.5 ml/kg/h for 6 hours post-operatively
If at least one of these measures is present by the 7 day assessment, a patient will be
considered to have developed CSA-AKI.
Randomized Phase II Clinical Trial of AZD6244 Hydrogen Sulfate (NSC-748727) and MK-2206 (NSC-749607) vs mFOLFOX in Patients With Metastatic Pancreatic Cancer After Prior Chemotherapy
PRIMARY OBJECTIVES:
I. To assess overall survival in patients with metastatic pancreatic cancer treated with the
combination of AZD6244 hydrogen sulfate (selumetinib) and MK-2206 (Akt inhibitor MK2206)
compared to those treated with mFOLFOX.
SECONDARY OBJECTIVES:
I. To assess the frequency and severity of toxicity associated with the combination of
AZD6244 hydrogen sulfate and MK-2206 compared to those with mFOLFOX in this patient
population.
TERTIARY OBJECTIVES:
I. To assess progression free survival (PFS) in patients with metastatic pancreatic cancer
treated with the combination of AZD6244 hydrogen sulfate and MK-2206 compared to those
treated with mFOLFOX.
II. To assess objective tumor response in the subset of patients with measurable disease
(confirmed and unconfirmed complete and partial response) in patients with metastatic
pancreatic cancer treated with the combination of AZD6244 hydrogen sulfate and MK-2206
compared to those treated with mFOLFOX.
III. To bank tissue and blood for future translational medicine studies.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive oxaliplatin intravenously (IV) over 2 hours on days 1 and 15 and
fluorouracil IV over 46-48 hours on days 1-2 and 15-16 (mFOLFOX).
ARM II: Patients receive Akt inhibitor MK2206 orally (PO) on days 1, 8, 15, and 22, and
selumetinib PO daily on days 1-28.
In all arms, courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for up to 3
years.
A Phase II Study of the Orally Administered Negative Enantiomer of Gossypol (AT-101) in Patients With Advanced Adrenocortical Carcinoma (ACC)
PRIMARY OBJECTIVE:
I. To determine the proportion of patients with recurrent, metastatic, or primary
unresectable adrenocortical carcinoma who achieve an objective response to R-(-)-gossypol
acetic acid.
SECONDARY OBJECTIVES::
I. To evaluate the safety of this drug in these patients. II. To determine the
progression-free and overall survival of these patients.
OUTLINE: This is a multicenter study.
Patients receive oral R-(-)-gossypol acetic acid once daily on days 1-21. Treatment repeats
every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for up to 2
years.
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