Here are the studies that match your search criteria. If you are interested in participating, please reach out to the contact listed for the study. If no contact is listed, contact us and we'll help you find the right person.
Prostate Oncologic Therapy While Ensuring Neurovascular Conservation (POTEN-C) (POTEN-C)
Reduction of dose to or 'sparing' of neurovascular structures during stereotactic ablative
body radiotherapy (SAbR) for localized prostate cancer will improve retention of sexual
potency, while retaining excellent oncologic control and other secondary health-related
quality of life (HRQOL) endpoints.
Primary Objectives:
• To compare the decline in patient health-related quality of life (HRQOL) instrument-defined
erectile dysfunction following stereotactic ablative body radiotherapy (SAbR) with or without
neurovascular sparing
Secondary Objectives:
- Assess acute (within 3 months of treatment) and chronic (>3 months after treatment) SAbR
related GU and GI toxicities, as well as serial impact on HRQOL metrics over time
- Assess biochemical progression free survival, local recurrence, distant recurrence, and
survival
- Evaluate simplified 'practical' secondary HRQOL sexual potency endpoints that can be
compared to prior literature.
Exploratory Objectives:
- Evaluate feasibility of MRI BOLD/TOLD to be integrated as hypoxia monitoring sequences
to standard already planned diagnostic and/or treatment planning MRI on the study in
five patient pilot.
- Evaluate quality of spacer placement and its effect on dose to neurovascular structures
- Evaluate rate local recurrence in the area of sparing adjacent to the neurovascular
elements by biopsy in those with biochemical progression.
1. Age ≥ 18 years.
2. Appropriate staging studies identifying patient as AJCC 7th edition clinical stage T1
(a, b, or c) or T2 (a, b, or c) adenocarcinoma of the prostate gland. The patient
should not have direct evidence of regional or distant metastases after appropriate
staging studies. See Appendix I for details on AJCC 7th Edition staging criteria.
Histologic confirmation of cancer will be required by biopsy performed within 12
months of registration. T-staging may be assessed by multi-parametric imaging alone if
digital rectal examination was deferred.
3. The patient's Zubrod performance status must be 0-2 (see Appendix II for definition).
4. The Gleason summary score should be less than or equal to 7 [Grade group 1 (Gleason
3+3=6), group 2 (Gleason 3+4=7), and group 3 (Gleason 4+3=7) are allowed]. See
Appendix III for details on definitions. While a template biopsy is recommended, it is
not required in the case of MRI fusion biopsy performed on all dominant MR lesions
(defined as PIRADS v2 4-5).
5. Baseline AUA symptom score ≤19 (see Appendix IV for questionnaire) without need for
maximum medical therapy (specifically, not on tamsulosin 0.8mg daily).
6. EPIC sexual domain composite score 60-100 (see Appendix V).
7. Multi-parametric MRI evaluation of the prostate is required for this study within 12
months of registration. Gross radiographic disease on MRI (defined as PIRADS v2 score
3-5) must be > 5mm at minimum distance from at least one side's neurovascular bundle,
which is typically the closest of the neurovascular elements to the prostate.
8. The serum PSA should be less than or equal to 20 ng/ml within 90 days of registration.
-Study entry PSA must not be obtained during the following time frames: (1) 10-day
period following prostate biopsy; (2) following initiation of ADT or anti-androgen
therapy; (3) within 30 days after discontinuation of finasteride; (4) within 90 days
after discontinuation of dutasteride; (5) within 5 days of a digital rectal
examination (which is not a required exam on the protocol).
9. Ultrasound or MRI based volume estimation of prostate gland ≤ 80 grams. Cytoreduction
therapy (finasteride or dutasteride only) may be considered for those with >60 gram
size.
10. All patients must be willing and capable to provide informed consent to participate in
the protocol within the 30 days prior to registration.
Exclusion Criteria:
1. Subjects with clinical (digital rectal examination) evidence of extraprostatic
extension (T3a) or seminal vesicle involvement (T3b). MRI evidence of
equivocal/potential but not definite extraprostatic extension is allowed, as long as
it is unilateral and not on the side of the gland proposed for neurovascular element
sparing. In equivocal cases of potential extracapsular extension on MRI only,
discretion is left to the treating physician.
2. MRI evidence of gross disease (defined as PIRADS v2 score 3-5 lesions) ≤5mm of BOTH
neurovascular bundles, which are the most proximate of the neurovascular elements
planned for sparing on this protocol.
3. Patients with all three intermediate risk factors (PSA >10 and ≤ 20, Gleason 7,
clinical stage T2b-T2c) who ALSO have ≥50% of the number of their template biopsy
cores positive for cancer are ineligible.
4. Inability to undergo multi-parametric MRI.
5. Evidence of metastatic disease. Note bone scan is not required for this study given
the low-intermediate NCCN risk cohort to be enrolled.
6. Evidence of clinical nodal involvement of the pelvis. Biopsy is required for lymph
nodes over ≥1.5cm in short-axis measured size.
7. No currently active ADT or anti-androgen therapy at time of registration is allowed.
Further, no more than 3 cumulative months of prior ADT or anti-androgen therapy is
allowed. If either has been used by the patient, there must be a demonstration of
testosterone recovery (>50ng/dL serum blood level), EPIC sexual domain score ≥60, and
at least 1 month between demonstration of testosterone recovery and study registration
(any one measurement of testosterone recovery suffices).
8. Testosterone ≤ 50 ng/dL (any one measurement >50 ng/dL suffices for inclusion) within
90 days of study entry.
9. Subjects who have had previous pelvic radiotherapy or have had chemotherapy or surgery
for prostate cancer.
10. Subjects who have plans to receive other concomitant or post treatment adjuvant
antineoplastic therapy while on this protocol including surgery, cryotherapy,
conventionally fractionated radiotherapy, hormonal therapy, or chemotherapy given as
part of the treatment of prostate cancer.
11. Subjects who have undergone previous transurethral resection of the prostate (TURP)
within 1 year of enrollment or ablative procedures to the prostate for benign
prostatic hyperplasia or other conditions (i.e. cryotherapy, HIFU).
12. Subjects who have baseline severe urinary symptoms, as defined by AUA symptom score
>19 (alpha-blocker medication allowed except if taking tamsulosin 0.8mg daily at
baseline which indicates compensated severe symptoms and also can affect sexual
function).
13. Subjects who have a history of significant psychiatric illness that would confound
informed consent.
14. Severe, active co-morbidity, defined as follows:
1. Unstable angina and/or congestive heart failure requiring hospitalization within
the last 6 months
2. Myocardial infarction within the last 6 months
3. Acute bacterial or fungal infection requiring intravenous antibiotics at time of
registration
4. Patients with active inflammatory colitis (including Crohn's Disease and
ulcerative colitis) currently requiring systemic steroids and/or systemic
immunosuppression are not eligible.
15. Subjects with a known allergy to polyethylene glycol hydrogel (rectal spacer material)
or contraindication to spacer products (SpaceOAR).
16. Subjects with uncontrolled coagulation disorder which cannot be controlled with
anticoagulants.
17. Men active with partners of reproductive potential who do not agree that they will use
an effective contraceptive method during treatment and 6 months after treatment.
18. Men who require erectile function medication or aid to achieve an erection sufficient
for intercourse. Ability to achieve erection sufficient for intercourse without
medication or aid at least once time in the month prior to registration is sufficient
for inclusion.
19. Men who have clinically significant penile malformation (i.e. Peyronie's disease) or
history of penile implantation are excluded.
20. If DRE is performed, patient may not have palpable disease on side of gland to be
planned for neurovascular sparing. Given the poor accuracy of DRE, such a finding
should be confirmed by MRI and/or biopsy to harbor actual disease before excluding a
patient on this basis.
Digital Tomosynthesis Mammography and Digital Mammography in Screening Patients for Breast Cancer
This randomized phase III trial studies digital tomosynthesis mammography and digital
mammography in screening patients for breast cancer. Screening for breast cancer with
tomosynthesis mammography may be superior to digital mammography for breast cancer screening
and may help reduce the need for additional imaging or treatment.
• Women of childbearing potential must not be known to be pregnant or lactating
• Patients must be scheduled for, or have intent to schedule, a screening mammogram
• Patients must be able to tolerate digital breast tomosynthesis and full-field digital
mammographic imaging required by protocol.
• Patients must be willing and able to provide a written informed consent
• Patients must not have symptoms or signs of benign or malignant breast disease (eg,
nipple discharge, breast lump) warranting a diagnostic rather than a screening
mammogram, and/or other imaging studies (eg, sonogram); patients with breast pain are
eligible as long as other criteria are met
• Patients must not have had a screening mammogram within the last 11 months prior to
date of randomization
• Patients must not have previous personal history of breast cancer including ductal
carcinoma in situ
• Patients must not have breast enhancements (e.g., implants or injections)
• ANNUAL SCREENING REGIMEN ELIGIBILITY CHECK
• To be eligible for inclusion in the annual screening regimen one of the following
three conditions must be met in addition to the eligibility criteria above:
• Patients are pre-menopausal; OR
• Post-menopausal aged 45-69 with any of the following three risks factors:
• Dense breasts (BIRADS density categories c-heterogeneously dense or
d-extremely dense), or
• Family history of breast cancer (first degree relative with breast cancer),
or, positive genetic testing for any deleterious genes that indicate an
increased risk for breast cancer, or
• Currently on hormone therapy; OR
• Post-menopausal ages 70-74 with either of the following two risk factors:
• Dense breasts (BIRADS density categories c-heterogeneously dense or
d-extremely dense), or
• Currently on hormone therapy
• Postmenopausal women are defined as those with their last menstrual period more than
12 months prior to study entry; for the purpose of defining menopausal status for
women who have had surgical cessation of their periods, women who no longer have
menses due to hysterectomy and oophorectomy will be considered postmenopausal; women
who no longer have menses due to hysterectomy without oophorectomy will be considered
premenopausal until age 52 and postmenopausal thereafter
• All other postmenopausal women are eligible for inclusion in the biennial screening
regimen
• For those women who cannot be assigned to annual or biennial screening at the time of
study entry and randomization because they are postmenopausal, have no family history
or known deleterious breast cancer mutation, are not on hormone therapy AND have not
had a prior mammogram, breast density will be determined by the radiologist?s
recording of it at the time of interpretation of the first study screening
examination, either DM or TM; for those who are randomized to TM, radiologists will
assign BI-RADS density through review of the DM or synthetic DM portion of the TM
examination; such women cannot be part of the planned stratification by screening
frequency and are expected to represent far less than 1% of the Tomosynthesis
Mammographic Imaging Screening Trial (TMIST) population
• Breast density will be determined by prior mammography reports, when available; all
other risk factors used to determine patient eligibility for annual or biennial
screening will be determined by subject self-report
Procedure: Digital Mammography, Procedure: Digital Tomosynthesis Mammography, Other: Laboratory Biomarker Analysis
Breast Screening, Breast - Female
Digital Mammography, Breast Tomography, Screening Mammography, TMIST
Sleep for Stroke Management and Recovery Trial (Sleep SMART)
The purpose of this study is to determine whether treatment of obstructive sleep apnea (OSA)
with positive airway pressure starting shortly after acute ischemic stroke or high risk TIA
(1) reduces recurrent stroke, acute coronary syndrome, and all-cause mortality 6 months after
the event, and (2) improves stroke outcomes at 3 months in patients who experienced an
ischemic stroke.
1. TIA with ABCD2 ≥4 or ischemic stroke, within the prior 14 days.
Exclusion Criteria:
1. pre-event inability to perform all of own basic ADLs
2. unable to obtain informed consent from subject or legally authorized representative
3. incarcerated
4. known pregnancy
5. current mechanical ventilation (can enroll later if this resolves) or tracheostomy
6. current use of positive airway pressure, or use within one month prior to stroke
7. anatomical or dermatologic anomaly that makes use of CPAP interface unfeasible
8. severe bullous lung disease
9. history of prior spontaneous pneumothorax or current pneumothorax
10. hypotension requiring current treatment with pressors (can enroll later if this
resolves)
11. other specific medical circumstances that conceivably, in the opinion of the site PI,
could render the patient at risk of harm from use of CPAP
12. massive epistaxis or previous history of massive epistaxis
13. cranial surgery or head trauma within the past 6 months, with known or possible CSF
leak or pneumocephalus
14. recent hemicraniectomy or suboccipital craniectomy (i.e. those whose bone has not yet
been replaced), or any other recent bone removal procedure for relief of intracranial
pressure
15. current receipt of oxygen supplementation >4 liters per minute
16. current contact, droplet, respiratory/airborne precautions
Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen OIT in Food Allergic Participants (OUtMATCH)
This study is a multi-center, randomized, double-blind, placebo-controlled study in
participants 1 to less than 56 years of age who are allergic to peanut and at least two other
foods (including milk, egg, wheat, cashew, hazelnut, or walnut). While each participant may
be allergic to more than two other foods, the primary endpoint/outcome in this study will
only be assessed in peanut and two other foods for each participant. The primary objective of
the study is to compare the ability to consume foods without dose-limiting symptoms during a
double-blind placebo-controlled food challenge (DBPCFC), after treatment with either
omalizumab or placebo for omalizumab.
Individuals who meet all of the following criteria are eligible for enrollment as study
participants:
1. Participant and/or parent/legal guardian must be able to understand and provide
informed consent and/or assent, as applicable;
2. Peanut allergic: participant must meet all of the following criteria to minimize the
chance that the participant will develop natural tolerance to peanut over the course
of the study:
1. Positive skin prick test (SPT) defined as ≥4 mm wheal greater than saline
control) to peanut,
2. Positive peanut immunoglobulin E (IgE), ≥6 kUA/L, at Screening or within three
months of Screening, determined by ImmunoCap, and
3. Positive double-blind placebo-controlled food challenge (DBPCFC), defined as
experiencing dose-limiting symptoms at a single dose of ≤100 mg of peanut
protein.
3. Allergic to at least two of the six other foods (milk, egg, wheat, cashew, hazelnut,
walnut): each participant must meet all of the following criteria for at least two of
the six other foods to minimize the chance that the participant will develop natural
tolerance to at least two of the six other foods over the course of the study:
1. Positive SPT (≥4 mm wheal) to food,
2. Positive food specific IgE (≥6 kUA/L) at Screening or within three months of
Screening, determined by ImmunoCap, and
3. Positive DBPCFC, defined as experiencing dose-limiting symptoms at a single dose
of ≤300 mg of food protein.
4. With body weight (as measured at Screening) and total serum IgE level (as measured
within three months of Screening) suitable for omalizumab dosing;
5. If female of child-bearing potential, must have a negative urine or serum pregnancy
test;
6. For women of childbearing potential, must agree to,during the treatment period and for
60 days after the last dose of study drug:
• remain abstinent (refrain from heterosexual intercourse), or
• use acceptable contraceptive methods (barrier methods, or
• oral, injected, or implanted hormonal methods of contraception, or
• other forms of hormonal contraception that have comparable efficacy).
7. Plan to remain in the study area of an OUtMATCH clinical research unit (CRU) during
the trial; and
8. Be willing to be trained on the proper use of an epinephrine autoinjector for the
duration of the study.
Exclusion Criteria:
Individuals who meet any of the following criteria are not eligible for enrollment as study
participants:
1. Inability or unwillingness of a participant and/or parent/legal guardian to give
written informed consent and/or assent or comply with the study protocol;
2. Clinically significant laboratory abnormalities at Screening;
3. Dose-limiting symptoms to the placebo portion of the Screening DBPCFC;
4. Sensitivity or suspected/known allergy to any ingredients (including excipients) of
the
• active or placebo oral food challenge (OFC) material,
• multi-allergen oral immunotherapy (OIT), or
• drugs related to omalizumab (e.g., monoclonal antibodies, polyclonal gamma
globulin).
• Note: Guidance for determination of sensitivity to excipients will be
detailed in the study's Manual of Procedures (MOP).
5. Poorly controlled atopic dermatitis (AD) at Screening, per the Principal
Investigator's PI's) discretion;
6. Poorly controlled or severe asthma/wheezing at Screening, defined by at least one of
the following criteria:
1. Global Initiative for Asthma (GINA) criteria regarding asthma control latest
guidelines,
2. History of two or more systemic corticosteroid courses within six months of
Screening or one course of systemic corticosteroids within three months of
Screening to treat asthma/wheezing,
3. Prior intubation/mechanical ventilation for asthma/wheezing,
4. One hospitalization or Emergency Department (ED) visit for asthma/wheezing within
six months of Screening,
5. Forced expiratory volume in one second (FEV1) <80 percent of predicted or
FEV1/forced vital capacity (FVC) <75 percent, with or without controller
medications (only for participants who are aged seven years or older and are able
to perform spirometry), or
6. Inhaled corticosteroid (ICS) dosing of >500 mcg daily fluticasone (or equivalent
ICS based on the National Institutes of Health, National Heart, Lung, and Blood
Institute (NHLBI) dosing chart).
7. History of severe anaphylaxis to participant-specific foods that will be used in this
study, defined as neurological compromise or requiring intubation;
8. Treatment with a burst of oral, intramuscular (IM), or intravenous (IV) steroids of
more than two days for an indication other than asthma/wheezing within 30 days of
Screening;
9. Currently receiving oral, intramuscular, or intravenous corticosteroids, tricyclic
antidepressants, or beta-blockers (oral or topical);
10. Past or current history of eosinophilic gastrointestinal (GI) disease within three
years of Screening;
11. Past or current history of cancer, or currently being investigated for possible
cancer;
12. Previous adverse reaction to omalizumab;
13. Past or current history of any immunotherapy to any of the foods being treated in this
study (e.g., OIT, sublingual immunotherapy [SLIT], EPIT) within 6 months of Screening;
14. Treatment with monoclonal antibody therapy, such as omalizumab (Xolair®), dupilumab
(Dupixent®), benralizumab (Fasenra™), mepolizumab (Nucala®), reslizumab (Cinqair®), or
other immunomodulatory therapy within six months of Screening;
15. Currently on "build-up phase" of inhalant allergen immunotherapy (i.e., has not
reached maintenance dosing). Note: Individuals tolerating maintenance allergen
immunotherapy can be enrolled;
16. Inability to discontinue antihistamines for the minimum wash-out periods required for
SPTs,or OFCs;
17. Current participation in another therapeutic or interventional clinical trial or
participation within 90 days of Screening;
18. Use of investigational drugs within 24 weeks of Screening;
19. Pregnant or breastfeeding, or intending to become pregnant during the study or within
60 days after the last dose of omalizumab or placebo for omalizumab;
20. Has a first-degree relative already enrolled in the study; or
21. Past or current medical problems (e.g., severe latex allergy), history of other
chronic diseases (other than asthma/wheezing, AD, or rhinitis) requiring therapy
(e.g., heart disease, diabetes), findings from physical assessment, or abnormalities
in clinical laboratory testing that are not listed above, which, in the opinion of the
PI, may:
• pose additional risks from participation in the study,
• may interfere with the participant's ability to comply with study requirements,
or
• may impact the quality or interpretation of the data obtained from the study.
Drug: Omalizumab, Drug: Placebo for Omalizumab, Drug: Multi-Allergen Oral Immunotherapy, Drug: Placebo for Multi-Allergen Oral Immunotherapy, Other: Double-Blind Placebo-Controlled Food Challenge Based Treatment
A Study of Daratumumab Plus Lenalidomide Versus Lenalidomide Alone as Maintenance Treatment in Participants With Newly Diagnosed Multiple Myeloma Who Are Minimal Residual Disease Positive After Frontline Autologous Stem Cell Transplant (AURIGA)
The purpose of this study is to evaluate conversion rate to minimal residual disease (MRD)
negativity following the addition of daratumumab to lenalidomide relative to lenalidomide
alone, when administered as maintenance treatment to anti-cluster of differentiation 38
(CD38) treatment naive participants with newly diagnosed multiple myeloma who are MRD
positive as determined by next generation sequencing (NGS) at screening, following high-dose
therapy (HDT) and autologous stem cell transplant (ASCT).
• Must have newly diagnosed multiple myeloma with a history of a minimum of 4 cycles of
induction therapy, have received high-dose therapy (HDT) and autologous stem cell
transplantation (ASCT) within 12 months of the start of induction therapy, and be
within 6 months of ASCT on the date of randomization
• Must have a very good partial response (VGPR) or better response assessed per
International Myeloma Working Group (IMWG) 2016 criteria at the time of randomization
• Must have archived bone marrow samples collected before induction treatment (that is,
at diagnosis) or before transplant (for example, at the end of induction) or have
existing results on the index multiple myeloma clone based on Adaptive
Biotechnologies' next generation sequencing (NGS)-based minimal residual disease (MRD)
assay. Archived bone marrow samples will be used for calibration of myeloma clonal
cells to facilitate assessment of primary end point by NGS. If an existing result on
index myeloma clone is available from Adaptive Biotechnologies' NGS-based MRD assay,
as part of institutional procedures, an archived bone marrow sample is not required as
long as Adaptive Biotechnologies is able to retrieve historical results on the index
myeloma clone form the clinical database. Any one of the following archived samples
are required: (a) Greater than 1 milliliter (mL) viable frozen bone marrow aspirated
aliquot (preferred) collected in an ethylenediaminetetra-acetic acid (EDTA) tube,
frozen, and stored at a temperature of -80 centigrade (°C), or; (b) Non-decalcified
diagnostic bone marrow aspirate clot sections (block or slides) for MRD assessment:
(i) A formalin fixed paraffin embedded (FFPE) block of bone marrow aspirate clot, or
slides (preferably 5, if available), 5 micrometer each, of non-decalcified bone
marrow, or; (ii) Slides (preferably 5, if available), bone marrow aspirate smear;
(iii) Please note, bone marrow core sections are not acceptable samples for analysis;
(iv) In exceptional circumstances when index myeloma clone cannot be identified from
the archived bone marrow sample, a post-transplant sample can be used to identify
myeloma clone with permission from the sponsor
• Must have residual disease as defined by detectable MRD (Adaptive Biotechnologies' NGS
based MRD assay)
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0,
1, or 2
Exclusion Criteria:
• A history of malignancy (other than multiple myeloma) unless all treatment of that
malignancy was completed at least 2 years before consent and the participant has no
evidence of disease before the of date of randomization. Exceptions are squamous and
basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other
non-invasive lesion that in the opinion of the investigator, with concurrence with the
sponsor's medical monitor, is considered cured with minimal risk of recurrence within
3 years
• Must not have progressed on multiple myeloma (MM) therapy at any time prior to
screening
• Have had prior treatment/therapy with: (a) Daratumumab or any other anti-cluster of
differentiation 38 (CD38) therapies, (b) Focal radiation therapy within 14 days prior
to randomization with the exception of palliative radiotherapy for symptomatic
management but not on measurable extramedullary plasmacytoma. Radiotherapy within 14
days prior to randomization on measurable extramedullary plasmacytoma is not permitted
even in the setting of palliation for symptomatic management, or (c) Plasmapheresis
within 28 days of randomization
• Be exhibiting clinical signs of meningeal or central nervous system involvement due to
multiple myeloma
• Have known chronic obstructive pulmonary disease (COPD) with a forced expiratory
volume in 1 second (FEV1) less than (<) 50 percent (%) of predicted normal
• Have known moderate or severe persistent asthma within the past 2 years or current
uncontrolled asthma of any classification
• Have any of the following: (a) Known history of seropositivity for human
immunodeficiency virus (HIV); (b) Seropositive for hepatitis B (defined by a positive
test for hepatitis B surface antigen [HBsAg]. Participants with resolved infection
(that is, participants who are HBsAg negative but positive for antibodies to hepatitis
B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs])
must be screened using real-time polymerase chain reaction (PCR) measurement of
hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded.
EXCEPTION: Participants with serologic findings suggestive of HBV vaccination
(anti-HBs positivity as the only serologic marker) AND a known history of prior HBV
vaccination, do not need to be tested for HBV DNA by PCR; (c) Seropositive for
hepatitis C (anti-hepatitis C virus [HCV] antibody positive or HCV-RNA quantitation
positive), except in the setting of a sustained virologic response, defined as
aviremia at least 12 weeks after completion of antiviral therapy)
Pioglitazone to Reduce Sympathetic Overactivity in CKD Patients
Chronic kidney disease (CKD) is associated with a higher risk of cardiovascular disease and
death. An overactive sympathetic nervous system in CKD patients is one of the major
mechanisms increasing the cardiovascular risks in this patient population. Recently, some
studies have shown that a drug typically used to improve glucose control (pioglitazone) may
also reduce sympathetic nerve activity and improve blood vessel function.
The goal of this study is to determine whether a short-term treatment with pioglitazone can
reduce sympathetic nerve impulses throughout the body in CKD patients.
• CKD patients classified as Stage 3 and 4 of National Kidney Foundation Classification
with estimated glomerular filtration rate (GFR) between 15 and 59 mL/min/1.73 m2
according to the Modification of Diet in Renal Disease (MDRD) formula based on serum
creatinine, age, gender, and race.
• Men and women 35 to 70 years of age
Exclusion Criteria:
• Allergy to Glitazones
• Myocardial infarction
• Heart failure
• Angina
• History of kidney stones
• Liver disease (abnormal liver enzymes)
• Anemia (hemoglobin <8 g/dl)
• Cancer with current treatment
• Previous organ transplantation
• Immunosuppressant therapy
• Human immunodeficiency virus infection
• Pregnancy or lactating
• Current tobacco use
• Dilantin and oral contraceptive usage due to potential drug interaction with
glitazones
• Self-identified history of hypoglycemia
Drug: Pioglitazone, Other: Placebo
Chronic Kidney Diseases, Kidney
blood pressure, pioglitazone, hypertension
UT Southwestern; Parkland Health & Hospital System
A Research Study to Look at How Semaglutide Compared to Placebo Affects Diabetic Eye Disease in People With Type 2 Diabetes (FOCUS)
This study will look at the long-term effects of semaglutide (active medicine) on diabetic
eye disease when compared to placebo (dummy medicine). The study will be performed in people
with type 2 diabetes. Participants will either get semaglutide or placebo in addition to
their diabetes medicines - which treatment the participant gets is decided by chance.
Participants will inject the study medicine using a pen-injector. The medicine must be
injected in a skin fold in the stomach, thigh or upper arm once a week. The study will last
for 5 years.
• Male or female, age greater than or equal to 18 years at the time of signing informed
consent
• Diagnosed with type 2 diabetes mellitus greater than or equal to 10 years prior to the
day of screening
• HbA1c of 7.0-10.0% (53-86 mmol/mol) (both inclusive)
• Eye inclusion criteria (both eyes must meet all criteria):
• Early Treatment Diabetic Retinopathy Study (ETDRS) level of 10-75 (both inclusive)
evaluated by fundus photography and confirmed by central reading centre
• No ocular or intraocular treatment for diabetic retinopathy or diabetic macular oedema
twelve months prior to the day of screening
• No anticipated need for ocular or intraocular treatment for diabetic retinopathy or
diabetic macular oedema within six months after randomisation
• Best-corrected visual acuity greater than or equal to 30 letters using the ETDRS
visual acuity protocol
• No previous treatment with pan-retinal laser photocoagulation
• No substantial non-diabetic ocular condition that, in the opinion of the
ophthalmologist, would impact diabetic retinopathy or diabetic macular oedema
progression during the trial
• No substantial media opacities that would preclude successful imaging
Exclusion Criteria:
• Any of the following: myocardial infarction, stroke, hospitalization for unstable
angina pectoris or transient ischaemic attack within the past 60 days prior to the day
of screening
• Planned coronary, carotid or peripheral artery revascularisation known on the day of
screening
• Subjects presently classified as being in New York Heart Association (NYHA) Class IV
• Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of eGFR
less than 30 ml/min/1.73 m^2
• Personal or first degree relative(s) history of multiple endocrine neoplasia type 2 or
medullary thyroid carcinoma
• Presence or history of malignant neoplasms within the past 5 years prior to the day of
screening. Basal and squamous cell skin cancer and any carcinoma in-situ are allowed
• Female who is pregnant, breast-feeding or intends to become pregnant or is of
child-bearing potential and not using highly effective contraceptive methods
• Current or previous (within 30 days before screening) treatment with any glucagon like
peptide-1 (GLP-1) receptor agonist or dipeptidyl peptidase-4 (DPP-4) inhibitor
• Receipt of any investigational medicinal product within 30 days before screening
• Previous participation in this trial. Participation is defined as randomisation
• Known or suspected hypersensitivity to trial products or related products
• Any disorder, which in the investigator's opinion might jeopardise subject's safety or
compliance with the protocol
Drug: Semaglutide, Drug: Placebo (semaglutide)
Diabetes Mellitus, Type 2
UT Southwestern; Parkland Health & Hospital System
Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
This phase II trial studies how well cabozantinib works in combination with nivolumab and
ipilimumab in treating patients with rare genitourinary (GU) tumors that have spread to other
places in the body. Cabozantinib may stop the growth of tumor cells by blocking some of the
enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab
and ipilimumab, may help the body's immune system attack the cancer, and may interfere with
the ability of tumor cells to grow and spread. Giving cabozantinib, nivolumab, and ipilimumab
may work better in treating patients with genitourinary tumors that have no treatment options
compared to giving cabozantinib, nivolumab, or ipilimumab alone.
• Metastatic disease defined as new or progressive lesions on cross-sectional imaging or
bone scan. Patients must have at least:
• One measurable site of disease as per Response Evaluation Criteria in Solid
Tumors (RECIST) version (v) 1.1
• One bone lesion on bone scan (tec99 or sodium fluoride [NaF] positron emission
tomography [PET]/computed tomography [CT], CT, or magnetic resonance imaging
[MRI]) for the bone-only cohort
• Histologically confirmed diagnosis of one of the following metastatic cohorts:
• Small cell/ neuroendocrine carcinoma of the bladder •All urothelial
carcinomas with any amount of neuroendocrine differentiation (including
small cell differentiation) will be included. If the tumor is purely
neuroendocrine, metastasis from another site of origin should be clinically
excluded.
• Adenocarcinoma of the bladder, or urachal adenocarcinoma, or bladder/urethra
clear cell adenocarcinoma •must be pure (per World Health Organization
[WHO] definition), (i.e. urothelial carcinoma with glandular differentiation
is not considered a pure adenocarcinoma.
• Squamous cell carcinoma of the bladder •must be pure (i.e. urothelial
carcinoma with squamous differentiation is not considered a pure squamous
cell carcinoma).
• Plasmacytoid urothelial carcinoma •Tumor should show predominantly > or
equal ~50% plasmacytoid histology (including all types of discohesive
growth, such as tumors with signet-ring and/or rhabdoid features as well).
• Any penile cancer
• Sarcomatoid renal cell carcinoma •Tumor should be predominantly sarcomatoid
~50% (including rhabdoid differentiation) is also unclassified renal cell
carcinomas (RCCs): all (assuming they are high grade with metastasis)
malignant angiomyolipomas are allowed.
• Sarcomatoid urothelial carcinoma •Tumor should show predominantly ~ 50%
sarcomatoid differentiation.
• Renal medullary carcinoma •Per WHO definition, ideally confirmed with
immunostains.
• Renal collecting duct carcinoma •Per WHO definition (medullary involvement,
predominant tubular morphology, desmoplastic stromal reaction, high grade
cytology, infiltrative growth pattern, and absence of other renal cell
carcinoma subtype or urothelial carcinoma).
• Bone only urothelial carcinoma or other non-prostate GU tumor
• Urethra carcinoma •May be of any histology but if urothelial carcinoma then
must be isolated to the urethra and not have metachronous or synchronous
urothelial carcinoma of the bladder.
• Other miscellaneous histologic variants of the urothelial carcinoma, such
as, but not limited to: micropapillary (Tumor should show predominantly > or
equal 50% micropapillary architecture), giant cell, lipid-rich, clear cell
and nested variants (Tumor should predominantly > or equal 50% show these
features), large cell neuroendocrine carcinoma, lymphoepithelioma-like
carcinoma and mixed patterns will be considered, as well as small cell
neuroendocrine prostate cancer (Only treatment-naïve primary small cell of
prostate with any amount of small cell component allowed. Post-treatment
small cell prostatic carcinomas are not allowed), Malignant testicular
Sertoli or Leydig cell tumors, and papillary and chromophobe RCC.
• Note: Translocation positive renal cell carcinoma patients are
eligible. However, AREN1721 should be considered before this trial.
• Hematoxylin and eosin (H&E) slides from diagnostic tumor tissue for retrospective
central pathology review
• Patients may have received up to 2 systemic anti-cancer treatments or be treatment
naive. Patients with small cell carcinoma should have received a platinum-based
combination regimen either as neoadjuvant, adjuvant or first-line treatment). Patients
in the bone-only cohort may be urothelial carcinoma histology but must receive
standard cisplatin-based chemotherapy (if cisplatin-eligible).
• Patients must be able to swallow oral formulation of the tablets
• Karnofsky performance status >= 80%
• Absolute neutrophil count (ANC) >= 1,000/mcL
• Platelet count >= 75,000/mcL
• Total bilirubin =< 1.5 x upper limit of normal (ULN). For subjects with known
Gilbert's disease or similar syndrome with slow conjugation of bilirubin, total
bilirubin =< 3.0 mg/dL
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x institutional
upper limit of normal (ULN) (or =< 5 x ULN for patients with liver metastases or
Gilbert's disease)
• Creatinine =< 1.5 x upper limit of normal (ULN) OR creatinine clearance >= 40
mL/min/1.73 m^2 (calculated using the Chronic Kidney Disease Epidemiology [CKD-EPI]
equation or Cockcroft-Gault formula) for patients with creatinine levels above
institutional normal
• Hemoglobin >= 9 g/dL (transfusion of packed red blood cells [PRBCs] allowed)
• Serum albumin >= 3.2 g/dL
• Lipase and amylase =< 2.0 x ULN and no radiologic (on baseline anatomical imaging) or
clinical evidence of pancreatitis
• Prior treatment with MET or VEGFR inhibitors is allowed. However, prior cabozantinib
will not be allowed. Also, patients that have received both prior MET or VEGF and
prior PD-1/PD-L1/CTLA-4 (sequentially or in combination) are also not allowed
• Prior treatment with any therapy on the PD-1/PD-L1 axis or anti- CTLA-4/CTLA-4
inhibitors is allowed, either in the perioperative or in the metastatic setting.
However, patients that have received both prior MET or VEGF and prior
PD-1/PD-L1/CTLA-4 (sequentially or in combination) are not allowed
• Human immunodeficiency virus (HIV)-positive patients are eligible if on stable dose of
highly active antiretroviral therapy (HAART), no clinically significant drug-drug
interactions are anticipated with the current HAART regimen, CD4 counts are greater
than 350 and viral load is undetectable
• Patients with rheumatoid arthritis and other rheumatologic arthropathies, Sjogren's
syndrome and psoriasis controlled with topical medication only and patients with
positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies etc.
are eligible but should be considered for rheumatologic evaluation for the presence of
target organ involvement and potential need for systemic treatment
• Patients with vitiligo, endocrine deficiencies including thyroiditis managed with
replacement hormones or medications (e.g. thyroiditis managed with propylthiouracil
[PTU] or methimazole) including physiologic oral corticosteroids are eligible
• Patients who have evidence of active or acute diverticulitis, intra-abdominal abscess,
and gastrointestinal (GI) obstruction, within 12 months are not eligible
• Women of childbearing potential must have a negative pregnancy test =< 7 days prior to
registration
• Women of childbearing potential include women who have experienced menarche and
who have not undergone successful surgical sterilization (hysterectomy, bilateral
tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Post
menopause is defined as amenorrhea >= 12 consecutive months. Note: women who have
been amenorrheic for 12 or more months are still considered to be of childbearing
potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens,
ovarian suppression or any other reversible reason
• Pregnant women may not participate in this study because with cabozantinib, nivolumab,
and ipilimumab have potential for teratogenic or abortifacient effects. Because there
is an unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with cabozantinib, nivolumab, and ipilimumab, breastfeeding
should be discontinued if the mother is treated with these agents
• The patient has received no cytotoxic chemotherapy (including investigational
cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 2
weeks before the first dose of study treatment
• The patient has received no radiation therapy:
• To the lungs and mediastinum or abdomen within 4 weeks before the first dose of
study treatment, or has ongoing complications, or is healing from prior radiation
therapy
• To brain metastasis within 3 weeks for whole-brain radiotherapy (WBXRT), and 2
weeks for stereotactic body radiation therapy (SBRT) before the first dose of
study treatment
• To the abdomen within 4 weeks before the first dose of study treatment, or has
ongoing complications, or is healing from prior radiation therapy
• To any other site(s) within 2 weeks before the first dose of study treatment
• The patient has received no radionuclide treatment within 6 weeks of the first dose of
study treatment
• The patient has received no prior treatment with a small molecule kinase inhibitor
within 14 days or five half-lives of the compound or active metabolites, whichever is
longer, before the first dose of study treatment
• The patient has received no prior treatment with hormonal therapy within 14 days or
five half-lives of the compound or active metabolites, whichever is longer, before the
first dose of study treatment. Subjects receiving gonadotropin-releasing hormone
(GnRH) agonists and antagonists are allowed to participate
• The patient has not received any other type of investigational agent within 14 days
before the first dose of study treatment
• The patient must have recovered to baseline or Common Terminology Criteria for Adverse
Events (CTCAE) =< grade 1 from toxicity due to all prior therapies except alopecia,
neuropathy and other non-clinically significant adverse events (AEs) defined as lab
elevation with no associated symptoms or sequelae
• The patient may not have active brain metastases or epidural disease. Patients with
brain metastases previously treated with whole brain radiation or radiosurgery who are
asymptomatic and do not require steroid treatment for at least 2 weeks before starting
study treatment are eligible. Neurosurgical resection of brain metastases or brain
biopsy is permitted if completed at least 3 months before starting study treatment.
Baseline brain imaging with contrast-enhanced computed tomography (CT) or magnetic
resonance imaging (MRI) scans for subjects with known brain metastases is required to
confirm eligibility
• No concomitant treatment with warfarin. Aspirin (up to 325 mg/day), thrombin or factor
Xa inhibitors, low-dose warfarin (=< 1 mg/day), prophylactic and therapeutic low
molecular weight heparin (LMWH) are permitted
• No chronic concomitant treatment with strong CYP3A4 inducers (e.g., dexamethasone,
phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St.
John's wort) or strong CYP3A4 inhibitors
• Because the lists of these agents are constantly changing, it is important to
regularly consult medical reference texts such as the Physicians' Desk Reference
may also provide this information. As part of the enrollment/informed consent
procedures, the patient will be counseled on the risk of interactions with other
agents, and what to do if new medications need to be prescribed or if the patient
is considering a new over-the-counter medicine or herbal product
• The patient has not experienced any of the following:
• Clinically-significant gastrointestinal bleeding within 6 months before the first
dose of study treatment
• Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood per day within 1 months
before the first dose of study treatment
• Any other signs indicative of pulmonary hemorrhage within 3 months before the
first dose of study treatment
• The patient has no tumor invading any major blood vessels
• The patient has no evidence of tumor invading the GI tract (esophagus, stomach, small
or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial
tumor within 28 days before the first dose of cabozantinib. Patients with rectal tumor
masses are not eligible.
• The patient has no uncontrolled, significant intercurrent or recent illness including,
but not limited to, the following conditions:
• Cardiovascular disorders including:
• Congestive heart failure (CHF): New York Heart Association (NYHA) class III
(moderate) or class IV (severe) at the time of screening.
• Concurrent uncontrolled hypertension defined as sustained blood pressure
(BP) > 150 mm Hg systolic, or > 90 mm Hg diastolic despite optimal
antihypertensive treatment within 7 days of the first dose of study
treatment
• The subject has a corrected QT interval calculated by the Fridericia formula
(QTcF) > 500 ms within 28 days before randomization. Note: if initial QTcF
is found to be > 500 ms, two additional electrocardiograms (EKGs) separated
by at least 3 minutes should be performed. If the average of these three
consecutive results for QTcF is =< 500 ms, the subject meets eligibility in
this regard
• Any history of congenital long QT syndrome
• Any of the following within 6 months before registration of study treatment:
• Unstable angina pectoris
• Clinically-significant cardiac arrhythmias (patients with atrial
fibrillation are eligible)
• Stroke (including transient ischemic attack [TIA], or other ischemic
event)
• Myocardial infarction
• Cardiomyopathy
• No significant gastrointestinal disorders particularly those associated with a
high risk of perforation or fistula formation including:
• Any of the following that have not resolved within 28 days before the first
dose of study treatment:
• Active peptic ulcer disease
• Acute diverticulitis, cholecystitis, symptomatic cholangitis or
appendicitis, or malabsorption syndrome
• None of the following within 2 years before the first dose of study
treatment:
• Abdominal fistula or genitourinary fistula
• Gastrointestinal perforation
• Bowel obstruction or gastric outlet obstruction
• Intra-abdominal abscess. Note: Complete resolution of an
intra-abdominal abscess must be confirmed prior to initiating treatment
with cabozantinib even if the abscess occurred more than 2 years before
the first dose of study treatment
• Disorders associated with a high risk of fistula formation including percutaneous
endoscopic gastrostomy (PEG) tube placement are not eligible
• No other clinically significant disorders such as:
• Severe active infection requiring IV systemic treatment within 14 days
before the first dose of study treatment
• Serious non-healing wound/ulcer/bone fracture within 28 days before the
first dose of study treatment
• History of organ or allogeneic stem cell transplant
• Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days
before the first dose of study treatment (for asymptomatic patients with an
elevated thyroid-stimulating hormone [TSH], thyroid replacement may be
initiated if clinically indicated without delaying the start of study
treatment)
• No history of major surgery as follows:
• Major surgery within 3 months of the first dose of cabozantinib; however, if
there were no wound healing complications, patients with rapidly growing
aggressive cancers, may start as soon as 6 weeks if wound has completely
healed post-surgery
• Minor surgery within 1 month of the first dose of cabozantinib if there were
no wound healing complications or within 3 months of the first dose of
cabozantinib if there were wound complications excluding core biopsies and
mediport placement
• Complete wound healing from prior surgery must be confirmed before the first
dose of cabozantinib irrespective of the time from surgery
• No history of severe hypersensitivity reaction to any monoclonal antibody
• No evidence of active malignancy, requiring systemic treatment within 2 years of
registration
• No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to cabozantinib, nivolumab, ipilimumab or other agents used in
study
• No positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus
ribonucleic acid (HCV antibody) indicating acute or chronic infection. If HBV sAG is
positive, subsequent ribonucleic acid (RNA) polymerase chain reaction (PCR) must be
negative
• No patients with active autoimmune disease or history of autoimmune disease that might
recur, which may affect vital organ function or require immune suppressive treatment
including systemic corticosteroids. These include, but are not limited to patients
with a history of immune related neurologic disease, multiple sclerosis, autoimmune
(demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic
autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue
diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis,
hepatitis; and patients with a history of toxic epidermal necrolysis (TEN),
Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the
risk of recurrence or exacerbation of disease
Ribociclib and Letrozole Treatment in Ovarian Cancer
The study evaluates the response to treatment with Ribociclib and Letrozole in patients with
low grade serous cancer of the ovary, fallopian tube or peritoneum.
Patients eligible for inclusion in this study must meet all of the following criteria:
1. Patient has signed the Informed Consent (ICF) prior to any screening procedures being
performed and is able to comply with protocol requirements.
2. Age > 18 years at time of study entry.
3. Willingness and ability to comply with study and follow-up procedures.
4. Histological confirmation of diagnosis of low-grade serous carcinoma of ovary,
fallopian tube or peritoneum; Original diagnosis of de novo low-grade serous carcinoma
or Original diagnosis of serous borderline tumor with subsequent diagnosis of
low-grade serous carcinoma.
• In order to prevent inclusion of patients with high-grade serous carcinoma,
diagnosis of low-grade serous carcinoma will be verified as part of screening review
by a gynecologic pathologist. Tissue for confirmation can be from primary tumor or
recurrence.
5. Patient must have recurrent, measurable disease by RECIST v1.1.
6. There are no restrictions on number of prior therapies.
7. Patient cannot have previously received a prior cyclin dependent kinase inhibitor
(CDKi). Patients who were treated with letrozole or another aromatase inhibitor for
other indications must have not taken the drug for 6 months prior to initiating
letrozole for this trial and may not have progressed on treatment.
8. Patients must not have remaining ovarian function to be included. In women who have at
least one retained ovary, menopause must be confirmed with laboratory confirmation.
Women who have ovarian function are eligible but must be placed on hormonal
suppression. Menopause must be confirmed with laboratory confirmation, to include an
estradiol level as this is assessed within 8 weeks of patient having been on
tamoxifen.
9. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
10. Resolution of all acute toxic effects of prior therapy or surgical procedures to
National Cancer Institute (NCI) CTCAE Grade ≤ 1. Patients with grade 1 taxane-induced
neuropathy, any grade alopecia, amenorrhea, or other toxicities not considered a
safety risk for the patient as per investigator's discretion are eligible. 1. Patient
has adequate bone marrow and organ function as defined by the following laboratory
values at screening:
• Absolute neutrophil count ≥1.5 × 109/L
• Platelets ≥100 × 109/L
• Hemoglobin ≥9.0 g/dL
• Potassium, total calcium (corrected for serum albumin), magnesium, sodium and
phosphorus within normal limits for the institution or corrected to within normal
limits with supplements before first dose of study medication
• INR ≤1.5 (unless patient is receiving permitted anticoagulants and the INR is
within the therapeutic range of intended use for that anticoagulant within 7 days
prior to the first dose of study drug). Serum creatinine <1.5 mg/dL or creatinine
clearance ≥50 mL/min
• In the absence of liver metastases, alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) <2.5 x ULN. If the patient has liver metastases, ALT and
AST <5 x ULN
• Total bilirubin < ULN; or total bilirubin ≤3.0 x ULN or direct bilirubin ≤1.5 x
ULN in patients with well-documented Gilbert's Syndrome.
12. Patient with available standard 12-lead ECG with the following parameters at screening:
• QTcF interval at screening <450msec (using Fridericia's correction)
• Resting heart rate 50-90bpm 13. Must be able to swallow ribociclib and letrozole
capsules/tablets. 14. Patients receiving tamoxifen or toremifine must have washout
period of 5 half-lives prior to randomization.
Patients eligible for this study must not meet any of the following criteria:
1. Patient has a known hypersensitivity to any of the excipients of ribociclib or
letrozole.
2. Patient has a concurrent malignancy or malignancy within 3 years prior to starting
study drug, with the exception of adequately treated, basal or squamous cell
carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
Patients with known brain metastases are excluded.
3. Patients with central nervous system (CNS) involvement unless they meet ALL of the
following criteria:
• At least 4 weeks from prior therapy completion (including radiation and/or
surgery) to starting the study treatment
• Clinically stable CNS tumor at the time of screening and not receiving steroids
and/or enzyme inducing anti-epileptic medications for brain metastases.
4. Patient has impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of the study drugs (e.g., ulcerative diseases,
uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel
resection).
5. Patient has a known history of HIV infection (testing not mandatory).
6. Patient has any other concurrent severe and/or uncontrolled medical condition that
would, in the investigator's judgment, cause unacceptable safety risks, contraindicate
patient participation in the clinical study or compromise compliance with the protocol
(e.g. chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled
fungal, bacterial or viral infections, etc.).
7. Clinically significant, uncontrolled heart disease and/or cardiac repolarization
abnormalities, including any of the following:
• History of acute coronary syndromes (including myocardial infarction, unstable
angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or
symptomatic pericarditis within 6 months prior to screening
• History of documented congestive heart failure (New York Heart Association
functional classification III-IV)
• Documented cardiomyopathy
• Left Ventricular Ejection Fraction (LVEF) <50% as determined by Multiple Gated
acquisition (MUGA) scan or echocardiogram (ECHO)
• Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia),
complete left bundle branch block, high-grade AV block (e.g. bifascicular block,
Mobitz type II and third-degree AV block)
• Long QT syndrome or family history of idiopathic sudden death or congenital long
QT syndrome, or any of the following:
• Risk factors for Torsades de Pointe (TdP) including uncorrected
hypocalcemia, hypokalemia or hypomagnesemia, history of cardiac failure, or
history of clinically significant/symptomatic bradycardia.
• Concomitant use of medication(s) with a known risk to prolong the QT
interval and/or known to cause Torsades de Pointe that cannot be
discontinued (within 5 half-lives or 7 days prior to starting study drug) or
replaced by safe alternative medication
• Inability to determine the QT interval on screening (QTcF, using
Fridericia's correction)
• Systolic blood pressure (SBP) >160 mmHg or <90 mmHg at screening
8. Patient is currently receiving any of the following medications and cannot be
discontinued 7 days prior to starting study drug (see Table 1 for details):
• Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit
hybrids, pummelos, star-fruit, and Seville oranges
• That have a narrow therapeutic window and are predominantly metabolized through
CYP3A4/5
• Herbal preparations/medications, dietary supplements.
9. Participation in other studies involving investigational drug(s) within 30 days prior
to randomization or within 5 half-lives of the investigational product (whichever is
longer) or participation in any other type of medical research judged not to be
scientifically or medically compatible with this study. If the patient is enrolled or
planned to be enrolled in another study that does not involve an investigational drug,
the agreement of Novartis study medical lead is required to establish eligibility.
10. Patient is currently receiving warfarin or other coumadin-derived anticoagulant for
treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight
heparin (LMWH) or fondaparinux is allowed. Direct-Acting Oral Anticoagulants (DOACS)
are permitted.
11. Patient is currently receiving or has received systemic corticosteroids ≤2 weeks prior
to starting study drug, or who have not fully recovered from side effects of such
treatment. The following uses of corticosteroids are permitted: a short duration (,5
days) of systemic corticosteriods; any durations of topical applications (e.g., for
rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local
injections (e.g., intra-articular)
12. Patient who has received radiotherapy ≤4 weeks or limited field radiation for
palliation ≤2 weeks prior to starting study drug, and who has not recovered to grade 1
or better from related side effects of such therapy (exceptions include alopecia)
and/or in whom ≥25% of the bone marrow (Ellis, 1961) was irradiated.
13. Patient has had major surgery within 14 days prior to starting study drug or has not
recovered from major side effects (tumor biopsy is not considered as major surgery).
14. Patient with a Child-Pugh score B or C.
15. Patients who are pregnant or breastfeeding.
16. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
throughout the study and for 3 weeks after study drug discontinuation. Highly
effective contraception methods include:
• Total abstinence when this is in line with the preferred and usual lifestyle of
the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of
contraception
• Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy), total hysterectomy, or tubal ligation at least six weeks before
taking study treatment. In case of oophorectomy alone, only when the reproductive
status of the woman has been confirmed by follow up hormone level assessment
Women are considered post-menopausal and not of child bearing potential if they have
had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile
(e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral
oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago.
In the case of oophorectomy alone, only when the reproductive status of the woman has
been confirmed by follow up hormone level assessment is she considered not of child
bearing potential.
17. Current use of food or drugs known to be potent CYP3A4 inhibitors, drugs known to be
potent CYP3A4 inducers, and drugs that are known to prolong the QT interval unless the
prohibited concomitant medication can be replaced by other drugs of less potential to
inhibit or induce CYP3A4 or prolong QT interval (See Appendix C for Prohibited
Concomitant Medications).
18. Patients whose tumors contain both low-grade serous carcinoma (LGSC) and high-grade
serous carcinoma (HGSC)
19. Patients with history of haemopoietic stem cell or bone marrow transplant.
Drug: Ribociclib, Drug: Letrozole
Low Grade Serous Carcinoma, Ovary
ovary, peritoneum, fallopian tube
UT Southwestern; Parkland Health & Hospital System
Regional Radiotherapy in Biomarker Low-Risk Node Positive and T3N0 Breast Cancer (TAILOR RT)
The purpose of this study is to compare the effects on low risk breast cancer receiving usual
care that includes regional radiation therapy, with receiving no regional radiation therapy.
Researchers want to see if not giving this type of radiation treatment works as well at
preventing breast cancer from coming back.
• Patients must be women with newly diagnosed histologically proven invasive carcinoma
of the breast with no evidence of metastases, staged as per site standard of care.
• Patients must have been treated by BCS or mastectomy with clear margins of excision.
Post-mastectomy positive margins for invasive disease and/or DCIS is not allowed.
Multifocal disease (i.e. the presence of two or more foci or breast cancer within the
same breast quadrant) and multicentric disease (i.e. the presence of two or more foci
of breast cancer in different quadrants of the same breast) are allowed.
• Patients with T3N0 disease are eligible.
• Patients with disease limited to nodal micrometastases are eligible
• Patients with nodal macrometastases (>2mm) treated by axillary dissection must have
1-3 positive axillary nodes (macrometastases, > 2 mm).
• Patients treated by mastectomy and SLNB alone must have only 1-2 positive axillary
nodes (macrometastases, > 2 mm).
• Patients must be ER ≥ 1% and HER2 negative on local testing
• Patients must have an Oncotype DX recurrence score ≤25 obtained from testing of breast
tumour tissue from a core biopsy or from the surgical specimen.
• Patient must consent to provision of, and investigator(s) must agree to submit to the
CCTG Central Tumour Bank, a representative formalin fixed paraffin block of tumour
tissue in order that the specific correlative marker assays described in the protocol
may be conducted
• Patient must consent to provision of samples of blood in order that the specific
correlative marker assays described in the protocol may be conducted.
• Patients must have had endocrine therapy initiated or planned for ≥ 5 years.
Premenopausal women will receive ovarian ablation plus aromatase inhibitor therapy or
tamoxifen if adjuvant chemotherapy was not administered. For all patients, endocrine
therapy can be given concurrently or following RT.
• Patients may or may not have had adjuvant chemotherapy.
• RT must commence within 16 weeks of definitive surgery if the patient is not treated
with chemotherapy. If adjuvant chemotherapy is given, RT must begin within 12 weeks
after the last dose. (Note: adjuvant chemotherapy may be ongoing at the time of
randomization). Definitive surgery is defined as the last breast cancer-related
surgery.
• Patient's ECOG performance status must be 0, 1 or 2.
• Patient's age must be ≥ 35 years.
• For the first 736 eligible English or French-speaking subjects who have agreed to
optional questionnaire completion: Patient is able (i.e. sufficiently fluent) and
willing to complete the quality of life, health utilities and lost productivity
questionnaires in either English or French (note: enrollment completed 2022Aug02)
• Patient consent must be appropriately obtained in accordance with applicable local and
regulatory requirements
• Patients must be accessible for treatment and follow-up. Investigators must assure
themselves the patients randomized on this trial will be available for complete
documentation of the treatment, adverse events, and follow-up.
• In accordance with CCTG policy, protocol treatment is to begin within 6 weeks of
patient randomization.
• Women of childbearing potential must have agreed to use an effective contraceptive
method. A woman is considered to be of "childbearing potential" if she has had menses
at any time in the preceding 12 consecutive months.
Exclusion Criteria:
• Patients with nodal disease limited to isolated tumour cells (pN0i+ < 0.2 mm).
• Patients with pT3N1 and pT4 disease (Note: patients with T3N0 are eligible).
• Any prior history, not including the index cancer, of ipsilateral invasive breast
cancer or ipsilateral DCIS treated with radiation therapy. (Patients with synchronous
or previous ipsilateral LCIS are eligible.)
• Synchronous or previous contralateral invasive breast cancer. (Patients with
contralateral DCIS are eligible unless previously treated with radiation.)
• History of non-breast malignancies except adequately treated non-melanoma skin
cancers, in situ cancers treated by local excision or other cancers curatively treated
with no evidence of disease for ≥ 5 years.
• Patients who are pregnant.
• Patients that have had prior ipsilateral chestwall/thoracic radiation.
• Patients treated with chemo or endocrine therapy administered in the neoadjuvant
setting for breast cancer. Endocrine therapy exposure 12 weeks or less prior to
surgery is permitted.
• Patients with serious non-malignant disease (e.g. cardiovascular, scleroderma etc.)
which would preclude RT.
• Patients with any serious active or co-morbid medical conditions, laboratory
abnormality, psychiatric illness, active or uncontrolled infections, or serious
illnesses or medical conditions that would prevent the patient from participating or
to be managed according to the protocol (according to investigator's decision).
Radiation: Radiation, Other: No Radiation
Breast Cancer, Breast - Female
UT Southwestern; Parkland Health & Hospital System
89Zr-DFO-Atezolizumab ImmunoPET/CT in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma
This is an exploratory clinical trial to assess the potential of 89Zr-DFO-Atezolizumab
Positron Emission Tomography/Computed Tomography (PET/CT) scans in patients with locally
advanced or metastatic renal cell carcinoma (RCC). This open label, nontherapeutic trial will
test the correlation of 89Zr-DFO-Atezolizumab immunoPET/CT with programmed death-ligand 1
(PD-L1) expression and the response to immune checkpoint inhibitor therapy in patients with
RCC. There will be two cohorts, one made up of patients with localized RCC who will undergo
89Zr-DFO-Atezolizumab PET/CT prior to nephrectomy and a second cohort of patients with
metastatic RCC who will undergo 89Zr-DFO-Atezolizumab PET/CT prior to treatment with an
immune checkpoint inhibitor.
• Patients with suspected renal cell carcinoma with planned surgery or patients with
metastatic RCC and a tissue diagnosis. (In standard clinical practice, biopsy is not
routinely performed in patients who will be having surgery).
• Ability to understand and the willingness to sign a written informed consent.
• Patient must be able to lie still for a 30 to 60 minute PET/CT scan.
• One of the following:
1. Patients with locally advanced RCC planned for surgery determined to be a high
risk of recurrence, defined by presence of at least clinical T2 or thioredoxin 1
(TxN1), OR patients with metastatic RCC for whom treatment with metastasectomy is
planned by the treating physician.
2. Patients with metastatic RCC for whom immuno-oncology (IO) therapy is planned.
• Women of child-bearing potential must agree to undergo and have documented a negative
pregnancy test on the day of 89Zr-DFO-Atezolizumab administration. A female of
child-bearing potential is any woman (regardless of sexual orientation, having
undergone a tubal ligation, or remaining celibate by choice) who meets the following
criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e.,
has had menses at any time in the preceding 12 consecutive months).
Exclusion Criteria:
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to
atezolizumab or any other chimeric or humanized antibodies.
• Uncontrolled severe and irreversible intercurrent illness or psychiatric
illness/social situations that would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital
abnormalities and the potential of this regimen to harm nursing infants.
• Significant autoimmune disease requiring treatment with either prednisone (or steroid
equivalent) at a dose > 10 mg/day or other immunosuppressive agents. (Replacement
steroid therapy is acceptable).
• Any patient for whom ICI therapy would be contraindicated for other reasons. Patients
with adverse reactions to ICI therapy may undergo second 89Zr-DFO-Atezolizumab
injection and PET/CT at the discretion of the treating physician considering that the
dose of antibody represents 1% of a single therapeutic dose and therefore unlikely to
cause adverse events.
• Subjects unable to provide informed consent.
• Subjects who are claustrophobic or have other contraindications to PET/CT.
• Subjects must not weigh more than the maximum weight limit for the table for the
PET/CT scanner where the study is being performed. (>200 kg or 440 lbs).
Trial of DFP-10917 vs Non-Intensive or Intensive Reinduction for AML Patients in 2nd/3rd/4th Salvage
Phase III, multicenter, randomized study with two arms (1:1 ratio) enrolling patients with
AML relapsed/refractory after 2, 3, or 4 prior induction regimens:
Experimental arm: DFP-10917 14-day continuous intravenous (IV) infusion at a dose of 6
mg/m²/day followed by a 14-day resting period per 28-day cycles.
Control arm: Non-Intensive Reinduction (LoDAC, Azacitidine, Decitabine, Venetoclax
Combination Regimens) or Intensive Reinduction (High and Intermediate Dose Cytarabine
Regimens), depending on the patient's prior induction treatment.
1. Histologically or pathologically confirmed diagnosis of AML based on WHO
classification that has relapsed after, or is refractory to, two, three, or four prior
induction regimens that may have included intensive chemotherapy (e.g., "7+3"
cytarabine and daunorubicin), epigenetic therapy (i.e., azacitidine or decitabine), or
targeted therapy (e.g., FLT-3, IDH-1/2, BCL-2, monoclonal antibody).
(Relapse is defined as reemergence of ≥5% leukemia blasts in bone marrow or ≥1% blasts
in peripheral blood ≥90 days after first CR or CR without complete platelet recovery
(CRp). Refractory AML is defined as persistent disease ≥28 days after initiation of
intensive induction therapy (up to two induction cycles) or relapse <90 days after
first CR or CRp. Refractory disease for patients undergoing hypomethylating agent
induction is defined as lack of remission following at least 2 cycles of epigenetic
therapy without reduction in bone marrow blast status.)
Patients with a history of IPSS-R high or very high risk MDS that transformed to AML
during treatment with hypomethylating drugs and then relapse following or are
refractory to a subsequent AML induction regimen may be enrolled as Second Salvage AML
patients. Additionally, patients with a history of MPN in accelerated phase (MPN-AP)
or high-risk primary myelofibrosis (PMF) that transformed to AML during treatment with
hypomethylating drugs and then relapse following or are refractory to a subsequent AML
induction regimen may be enrolled as Second Salvage AML patients.
2. Aged ≥ 18 years.
3. ECOG Performance Status of 0, 1 or 2.
4. Adequate clinical laboratory values (i.e., plasma creatinine <2.5 x upper limit of
normal (ULN) for the institution, bilirubin <2.5 x ULN, alanine transaminase (ALT) and
aspartate transaminase (AST) ≤2.5 x ULN).
5. Absence of active central nervous system (CNS) involvement by leukemia. Patients with
previously diagnosed CNS leukemia are eligible if the CNS leukemia is under control
and intrathecal treatment may continue throughout the study.
6. Absence of uncontrolled intercurrent illnesses, including uncontrolled infections,
cardiac conditions, or other organ dysfunctions.
7. Signed informed consent prior to the start of any study specific procedures.
8. Women of child-bearing potential must have a negative serum or urine pregnancy test.
9. Male and female patients must agree to use acceptable contraceptive methods for the
duration of the study and for at least one month after the last drug administration.
Exclusion Criteria:
1. The interval from prior treatment to time of study drug administration is < 2 weeks
for cytotoxic agents or < 5 half-lives for noncytotoxic agents. Exceptions: Use of
hydroxyurea is allowed before the start of study and is to be discontinued prior to
the initiation of study treatment. At the investigator's discretion, for patients with
significant leukocytosis that develops during the early treatment cycles, hydroxyurea
may be administered. The hydroxyurea should be discontinued as soon as clinically
appropriate.
2. Any >grade 1 persistent clinically significant toxicities from prior chemotherapy.
3. Inadequate Cardiac (left ventricular ejection fraction ≤40%) function.
4. White blood cell (WBC) count >15,000/μL (Note: Patients considered for possible
venetoclax-containing regimen must have WBC ≤10k/μL prior to initiating venetoclax
treatment).
5. For patients with prior hematopoietic stem cell transplant (HSCT):
1. Less than 3 months since HSCT
2. Acute Graft versus Host Disease (GvHD) >Grade 1
3. Chronic GvHD >Grade 1
6. Any concomitant condition that in the opinion of the investigator could compromise the
objectives of this study and the patient's compliance.
7. A pregnant or lactating woman.
8. Current malignancies of another type. Exceptions: Patients may participate if they
have previously treated and currently controlled prostate cancer, or adequately
treated in situ cervical cancer or basal cell skin cancer, or other malignancies with
no evidence of disease for 2 years or more.
9. Patient has acute promyelocytic leukemia (APL).
10. Patients with known HIV, active HBV or active HCV infection (note: testing for these
infections is not required). For patients with evidence of chronic hepatitis B virus
(HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if
indicated. Patients with a history of hepatitis C virus (HCV) infection must have been
treated and cured. For patients with HCV infection who are currently on treatment,
they are eligible if they have an undetectable HCV viral load.
11. Documented or known clinically significant bleeding disorder.
A Study of CC-99712, a BCMA Antibody-Drug Conjugate, in Participants With Relapsed and Refractory Multiple Myeloma
Study CC-99712-MM-001 is an open-label, Phase 1, dose escalation (Part A) and expansion (Part
B), First-in-Human (FIH) clinical study of CC-99712 in monotherapy or combination with
BMS-986405 in participants with relapsed and refractory multiple myeloma (MM). The dose
escalation part (Part A) of the study will evaluate the safety and tolerability of escalating
doses of CC-99712, administered intravenously (IV) in monotherapy (Arm 1) or combination with
BMS-986405 (Arm 2), to determine the maximum tolerated dose (MTD) of CC-99712 guided by a
Bayesian logistic regression model (BLRM). A modified accelerated titration design will also
be used for Arm 1 and Arm 2. The MTD may be established separately for CC-99712 administered
at Q3W and/ or Q4W schedules. The expansion part (Part B) will further evaluate the safety
and efficacy of CC-99712 in monotherapy (Arm 1) or combination (Arm 2) administered at or
below the MTD in selected expansion cohorts in order to determine the RP2D. One or more doses
or dosing regimens may be selected for cohort expansion. All participants will be treated
until confirmed disease progression per IMWG criteria, unacceptable toxicity, or
participants//Investigator decision to withdraw.
Participants must satisfy the following criteria to be enrolled in the study:
Inclusion
• Participant is ≥ 18 years of age at the time of signing the ICF.
• Participant has a history of multiple myeloma (MM) with relapsed and/or refractory
disease
• Participant must have measurable disease.
• Participant has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of
0 or 1.
Exclusion Criteria
• Participant has symptomatic central nervous system involvement of MM.
• Participant had a prior autologous stem cell transplant ≤ 3 months prior to starting
CC-99712.
• Participant had a prior allogeneic stem cell transplant with either standard or
reduced intensity conditioning ≤ 6 months prior to starting CC-99712 or is on systemic
immunosuppression for graft-versus host disease.
• Subject is a pregnant or lactating female.
• Subject has known human immunodeficiency virus (HIV) infection.
• Subject has active hepatitis B or C (HBV/HCV) infection.
Other protocol-defined inclusion/exclusion criteria apply
Drug: CC-99712, Drug: BMS-986405
Multiple Myeloma
Multiple Myeloma, Relapsed and refractory, CC-99712, BCMA, Antibody drug conjugate, BMS-986405
A Study of Erdafitinib Versus Investigator Choice of Intravesical Chemotherapy in Participants Who Received Bacillus Calmette-Guérin (BCG) and Recurred With High Risk Non-Muscle-Invasive Bladder Cancer (NMIBC)
The purpose of this study is to evaluate recurrence-free survival (RFS) in participants
treated with erdafitinib vs Investigator's Choice, for participants with high-risk
non-muscle-invasive bladder cancer (NMIBC) who harbor fibroblast growth factor receptor
(FGFR) mutations or fusions, and who recurred after bacillus calmette-guerin (BCG) therapy.
• Histologically confirmed, recurrent, non-muscle-invasive urothelial carcinoma of the
bladder. Variant pathology are allowed
• Tumor with specified fibroblast growth factor receptor (FGFR) mutations or fusions
• Bacillus Calmette- Guerin (BCG)-unresponsive after adequate BCG therapy or BCG
experienced participants
• Refuses or is not eligible for cystectomy (Cohort 1 and Cohort 2 only)
• Eastern Cooperative Oncology Group (ECOG) performance status Grade 0-1
• Must sign an informed consent form (ICF) (or their legally acceptable representative
must sign) indicating that he or she understands the purpose of, and procedures
required for, the study and is willing to participate in the study
• A woman of childbearing potential must have a negative pregnancy test (beta-hCG
[beta-human chorionic gonadotropin]) (urine or serum) within 7 days before
randomization (Cohort 1) or the first dose of study drug (Cohort 2 and Cohort 3)
• Adequate bone marrow, liver, and renal function as specified in the protocol
Exclusion Criteria:
• Histologically confirmed, muscle-invasive (T2 or higher stage) urothelial carcinoma of
the bladder
• Histopathology demonstrating any small cell component, pure adenocarcinoma, pure
squamous cell carcinoma, or pure squamous CIS of the bladder
• Prior treatment with an FGFR inhibitor
• Active malignancies other than the disease being treated under study. The only allowed
exceptions are: (a) skin cancer treated within the last 24 months that is considered
completely cured (b) adequately treated lobular carcinoma in situ (LCIS) and ductal
CIS (c) history of localized breast cancer and receiving antihormonal agents, or
history of localized prostate cancer (N0M0) and receiving androgen deprivation therapy
• Current central serous retinopathy or retinal pigment epithelial detachment of any
grade
A Study of the Efficacy and Safety of Relacorilant in Patients With Endogenous Cushing Syndrome (GRACE)
This is a Phase 3, double-blind, placebo-controlled, randomized-withdrawal study to assess
the efficacy, safety and pharmacokinetics (PK) of relacorilant in patients with endogenous
Cushing syndrome and concurrent type 2 diabetes mellitus/impaired glucose tolerance and/or
uncontrolled hypertension
• Has a confirmed diagnosis of endogenous Cushing syndrome
• Meets at least one of the following criteria:
• Has Type 2 diabetes mellitus
• Has impaired glucose tolerance
• Has hypertension
Exclusion Criteria:
• Has non-endogenous source of hypercortisolemia
• Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism
• Has poorly controlled hypertension
• Has poorly controlled diabetes mellitus
• Has severe renal insufficiency
Hyperinflation Respiratory Therapies in Cardiac Surgery Patients
The purpose of this prospective randomized clinical trial is to evaluate three different
types of hyperinflation respiratory therapies, Intermittent Positive Pressure Breathing
(IPPB), Intermittent positive end expiratory pressure (EzPAP), Metaneb. Investigators will
examine which hyperinflation therapy provides better lung expansion and may improve lung
recovery after surgery.
1. Age 18 years and older
2. Admitted to Cardiovascular ICU (CVICU) after coronary artery bypass grafting (CABG),
isolated valve repair/replacement, or CABG + valve repair/replacement
3. Cardiac surgery performed via median sternotomy
Exclusion Criteria:
1. BMI>40
2. Refusal to be consented
3. Prior or current lung transplant patients
CAMPFIRE: A Study of Ramucirumab (LY3009806) in Children and Young Adults With Desmoplastic Small Round Cell Tumor
This study is being conducted to test the safety and efficacy of ramucirumab in combination
with other chemotherapy in the treatment of relapsed, recurrent, or refractory desmoplastic
small round cell tumor (DSRCT) in children and young adults. This trial is part of the
CAMPFIRE master protocol which is a platform to accelerate the development of new treatments
for pediatric and young adult participants with cancer. Your participation in this trial
could last 12 months or longer, depending on how you and your tumor respond.
• Participants must have discontinued all previous treatments for cancer or
investigational agents ≥7 days after the last dose or per the type of previous
treatment as stated in the protocol and must have recovered from the acute effects to
≤Grade 2 for alopecia and decreased tendon reflex and to ≤Grade 1 for all other
effects at the time of enrollment, unless otherwise noted. Consult with the Lilly
clinical research physician or scientist for the appropriate length of time prior to
the first dose of study treatment.
• Participants with relapsed, recurrent, or refractory DSRCT.
• Participants must:
• Have measurable disease by Response Evaluation Criteria in Solid Tumors, Version
(RECIST) 1.1.
• Have received at least one prior line of systemic treatment (including
neoadjuvant and adjuvant chemotherapy). This prior treatment must include
approved therapies for which they are eligible, unless the participant is not a
suitable candidate for the approved therapy.
• Not be eligible for surgical resection at time of enrollment.
• Adequate cardiac function, defined as: Shortening fraction of ≥27% by echocardiogram,
or ejection fraction of ≥50% by gated radionuclide study.
• Adequate blood pressure (BP) control, defined as:
• Participants ≥18 years: Controlled hypertension defined as systolic BP ≤150
millimeters of mercury (mmHg) or diastolic BP ≤90 mmHg where standard medical
management is permitted. Please note that ≥2 serial BP readings should be
obtained and averaged to determine baseline BP.
• Participants <18 years: A BP ≤95th percentile for age, height, and gender
measured as described in National High Blood Pressure Education Program Working
Group (NHBPEPWG) on High Blood Pressure in Children and Adolescents (2004), where
standard medical management is permitted. Please note that ≥2 serial BP readings
should be obtained and averaged to determine baseline BP.
• Adequate hematologic function, as defined as:
• Absolute neutrophil count (ANC): ≥750/microliters (µL) granulocyte-colony
stimulating factor (G-CSF) permitted up to 48 hours prior. Participants with
documented history of benign ethnic neutropenia or other conditions could be
considered with a lower ANC after discussion with and approval from the Lilly
clinical research physician or scientist.
• Platelets: ≥75,000/cubic millimeters. Platelet transfusion permitted up to 72
hours prior.
• Hemoglobin: ≥8 grams per deciliter (g/dL) (≥80 g/liter). Transfusions to increase
the participant's hemoglobin level to at least 8 g/dL are permitted; however,
study treatment must not begin until 7 days after the transfusion, and complete
blood count criteria for eligibility are confirmed within 24 hr of first study
dose.
• Adequate renal function, as defined as:
• Creatinine clearance or radioscope glomerular filtration rate (GFR) ≥60
milliliters/minute/meters squared OR serum creatinine meeting the following
parameters:
• for participants ≥18 years of age serum creatinine ≤1.5×upper limit of
normal (ULN);
• for participants <18 years of age, serum creatinine based on age/gender as
follows: Age 1 to <2 years maximum serum creatinine 0.6, Age 2 to <6 years
maximum serum creatinine 0.8, Age 6 to <10 years maximum serum creatinine
1.0, Age 10 to <13 years maximum serum creatinine 1.2, Age 13 to <16 years
maximum serum creatinine 1.5 for males and 1.4 for females, Age 16 to <18
years maximum serum creatinine 1.7 for males and 1.4 for females.
• Urine protein meeting the following parameters:
• for participants ≥18 years of age: <2+ on dipstick or routine urinalysis. If
urine dipstick or routine analysis indicates proteinuria ≥2+, then a 24-hour
urine must be collected and must demonstrate <2 grams of protein in 24 hours
to allow participation in the study.
• for participants <18 years of age: ≤30 milligrams per deciliter urine
analysis or <2+ on dipstick. If urine dipstick or routine analysis indicates
proteinuria ≥2+, then a 24-hour urine must be collected and must demonstrate
<1 g of protein in 24 hours to allow participation in the study.
• Adequate liver function:
• Total bilirubin: ≤1.5×ULN. Except participants with document history of Gilbert
Syndrome who must have a total bilirubin level of <3.0×ULN.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): ≤2.5×ULN OR
≤5.0×ULN if the liver has tumor involvement.
• The participant has an adequate coagulation function as defined by International
Normalized Ratio ≤1.5 or prothrombin time ≤1.5×ULN, and partial thromboplastin time
≤1.5×ULN if not receiving anticoagulation therapy. For participants receiving
anticoagulants, exceptions to these coagulation parameters are allowed if they are
within the intended or expected range for their therapeutic use. Participants must
have no history of clinically significant active bleeding (defined as within 14 days
of first dose of study drug) or pathological condition that carries a high risk of
bleeding (for example, tumor involving major vessels or known esophageal varices).
• The participant has adequate hematologic and organ function ≤1 week (7 days) prior to
first dose of study drug.
• Female participants of childbearing potential must have a negative urine or serum
pregnancy test within 7 days prior to randomization. Male and female participants must
agree to use highly effective contraception for the duration of the study and up to 3
months following the last dose of ramucirumab and vinorelbine, and 12 months following
the last dose of cyclophosphamide in order to prevent pregnancy.
Exclusion Criteria:
• Participants with severe and/or uncontrolled concurrent medical disease or psychiatric
illness/social situation that in the opinion of the investigator could cause
unacceptable safety risks or compromise compliance with the protocol.
• Participants who have active infections requiring therapy.
• Participants with an active fungal, bacterial, and/or known severe viral
infection including, but not limited to, human immunodeficiency virus (HIV) or
viral (A, B, or C) hepatitis (screening is not required).
• Participants who have had allogeneic bone marrow or solid organ transplant are
excluded.
• Surgery: Participants who have had, or are planning to have, the following invasive
procedures are not eligible:
• Major surgical procedure, laparoscopic procedure, or significant traumatic injury
within 28 days prior to enrollment.
• Central line placement or subcutaneous port placement is not considered major
surgery.
• Core biopsy, fine needle aspirate, and bone marrow biopsy/aspirate are not
considered major surgeries.
• Surgical or other wounds must be adequately healed prior to enrollment.
• Bleeding and thrombosis:
• Participants with evidence of active bleeding or a history of significant (≥Grade
3) bleeding event within 3 months prior to enrollment are not eligible.
• Participants with a bleeding diathesis or vasculitis are not eligible.
• Participants with known or prior history in the prior 3 months of esophageal
varices are not eligible.
• Participants with a history of deep vein thrombosis requiring medical
intervention (including pulmonary embolism) within 3 months prior to study
enrollment are not eligible.
• Participants with a history of hemoptysis or other signs of pulmonary hemorrhage
within 3 months prior to study enrollment are not eligible.
• Cardiac:
• Participants with a history of central nervous system (CNS) arterial/venous
thromboembolic events (VTEs) including transient ischemic attack (TIA) or
cerebrovascular accident (CVA) within 6 months prior to study enrollment are not
eligible.
• Participants with myocardial infarction or unstable angina within the prior 6
months.
• Participants with New York Heart Association Grade 2 or greater congestive heart
failure (CHF).
• Participants with serious and inadequately controlled cardiac arrhythmia.
• Participants with significant vascular disease (eg, aortic aneurysm, history of
aortic dissection).
• Participants with clinically significant peripheral vascular disease.
• Participants who have a history of fistula, gastrointestinal (GI) ulcer or
perforation, or intra-abdominal abscess within 3 months of study enrollment are not
eligible.
• Participants with a history of hypertensive crisis or hypertensive encephalopathy
within 6 months of study enrollment are not eligible.
• Participants who have non-healing wound, unhealed or incompletely healed fracture, or
a compound (open) bone fracture at the time of enrollment are not eligible.
• Participants previously treated and progressed on combination cyclophosphamide and
vinorelbine regimen. Participants who received combination as maintenance therapy,
without progression, would be eligible.
• Participants with a known hypersensitivity to ramucirumab, cyclophosphamide,
vinorelbine or any of the excipients of the medicinal products.
• Hepatic impairment:
• Severe liver cirrhosis Child-Pugh Class B (or worse).
• Cirrhosis with a history of hepatic encephalopathy.
• Clinically meaningful ascites resulting from cirrhosis and requiring ongoing
treatment with diuretics and/or paracentesis.
• History of hepatorenal syndrome.
• The participant has a bowel obstruction, history or presence of inflammatory
enteropathy or extensive intestinal resection (eg, hemicolectomy or extensive small
intestine resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or
chronic diarrhea.
• The participant has a urinary outflow obstruction.
• The participant has Grade 2 hematuria or non-infectious cystitis at the time of
screening.
• Participants with central nervous system (CNS) involvement are ineligible.
HOPE in Action Trial of HIV+ Deceased Donor Liver Transplants for HIV+ Recipients
The primary objective of this study is to determine if an HIV-infected donor liver (HIVD+)
transplant is safe with regards to major transplant-related and HIV-related complications
• Participant meets the standard criteria for liver transplant at the local center.
• Participants being listed for a simultaneous liver kidney (SLK) are eligible if
participants meet the standard criteria for both organs.
• Participant is able to understand and provide informed consent.
• Participant meets with an independent advocate per the HIV Organ Policy Equity (HOPE)
Act Safeguards and Research Criteria.
• Documented HIV infection (by any licensed assay or documented history of detectable
HIV-1 RNA).*
• Participant is ≥ 18 years old.
• Opportunistic complications: prior history of certain opportunistic infections is not
an exclusion if the participant has received appropriate therapy and has no evidence
of active disease. Medical record documentation should be provided whenever possible.
• CD4+ T-cell count: ≥ 100/µL within 16 weeks prior to transplant if no history of
AIDS-defining infection; or ≥ 200 μL if history of opportunistic infection is present.
• HIV-1 RNA is below 50 RNA/mL.* Viral blips between 50-400 copies will be allowed as
long as there are not consecutive measurements > 200 copies/mL. *Organ recipients who
are unable to tolerate anti-retroviral therapy (ART) due to organ.
failure or recently started ART may be eligible despite a detectable viral load if safe and
effective ART to be used by the recipient after transplantation is described.
• Participant must have or be willing to start seeing a primary medical care provider
with expertise in HIV management.
• Participant is willing to comply with all medications related to participant's
transplant and HIV management.
• For participants with a history of aspergillus colonization or disease, no current
clinical evidence of active disease.
• Agreement to use contraception.
• Participant is not suffering from significant wasting (e.g. body mass index < 21)
thought to be related to HIV disease.
Exclusion Criteria:
• Participant has a history of progressive multifocal leukoencephalopathy (PML), or
primary central nervous system (CNS) lymphoma.*
• Participant is pregnant or breastfeeding. (Note: Participants who become pregnant
post-transplant will continue to be followed in the study and will be managed per
local site practice. Women that become pregnant should not breastfeed.)
• Past or current medical problems or findings from medical history, physical
examination or laboratory testing that are not listed above, which, in the opinion of
the investigator, may pose additional risks from participation in the study, may
interfere with the participant's ability to comply with study requirements or that may
impact the quality or interpretation of the data obtained from the study.
Gemcitabine and Cisplatin Without Cystectomy for Patients With Muscle Invasive Bladder Urothelial Cancer and Select Genetic Alterations
This phase II trial studies how well gemcitabine hydrochloride and cisplatin work in treating
participants with invasive bladder urothelial cancer. Drugs used in chemotherapy, such as
gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor
cells, either by killing the cells, by stopping them from dividing, or by stopping them from
spreading.
• Step 1 Patient Registration Eligibility Criteria
• Histologically confirmed muscle-invasive urothelial carcinoma of the bladder.
Urothelial carcinoma invading into the prostatic stroma with no histologic muscle
invasion is allowed, provided the extent of disease is confirmed via imaging and/or
examination under anesthesia (EUA). The diagnostic TURBT sample must have been
obtained within 60 days prior to registration
• 20 unstained slides (10 micron thickness) of formalin-fixed paraffin-embedded (FFPE)
pre-treatment diagnostic transurethral resection (TUR) specimen available (for
sequencing), with 2 (5 micron) slides at the start and end of the 20 slides, for a
total of 22 unstained slides. An FFPE block is also acceptable
• Clinical stage T2-T4aN0/xM0 disease
• Medically appropriate candidate for radical cystectomy as assessed by surgeon
• No concomitant multifocal carcinoma in situ; a single focus is allowed
• A single muscle-invasive bladder tumor measuring ≤5 cm in size as defined by the
surgeons at cystoscopic evaluation. When documented, pathologic size at cystoscopy and
TURBT will take precedence over radiographic measurements of tumor size.
• No clinical or radiographic evidence for locally advanced or metastatic disease
• No prior anti-PD-1 or anti PD-L1 therapies, or systemic chemotherapy within the past 5
years (prior intravesical induction immunotherapy for non-muscle invasive disease is
allowed, defined as BCG x6 doses and maintenance therapy); BCG refractory disease,
defined as disease recurrence within 3 months of BCG therapy, is not allowed.
Intravesical chemotherapy is allowed.
• No prior radiation therapy to the bladder or prostate
• No major surgery or radiation therapy =< 4 weeks of registration (TURBT is allowed).
• Not pregnant and not nursing. This study involves an agent that has known genotoxic,
mutagenic and teratogenic effects. For women of childbearing potential only, a
negative pregnancy test done =< 14 days prior to registration is required
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Absolute neutrophil count (ANC) >= 1,000/mm^3
• Platelet count >= 100,000/mm^3
• Calculated creatinine clearance ≥ 55 mL/min using formula per institutional standard
or investigator's discretion. The same formula should be used to calculate all
subsequent creatinine clearances.
• Total bilirubin =< 1.5 x upper limit of normal (ULN)
* (For patients with documented Gilbert's syndrome Total Bilirubin =< 3 x ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
• Alkaline phosphatase =< 2.5 x ULN
• No evidence of New York Heart Association (NYHA) functional class III or IV heart
disease
• No ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Terminology
Criteria for Adverse Events (CTCAE) version 5.0 grade >= 2
• No pre-existing sensory grade >= 2 neuropathy
• No pre-existing grade >= 2 hearing loss
• No serious intercurrent medical or psychiatric illness, including serious active
infection
• None of the following within the 6 months prior to study drug administration:
myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
graft, symptomatic congestive heart failure, cerebrovascular accident, or transient
ischemic attack
• No known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
(AIDS)-related illness or other active infection. HIV-positive patients on combination
antiretroviral therapy are ineligible because of the potential for pharmacokinetic
interactions with the drugs used in this trial. In addition, these patients are at
increased risk of lethal infections when treated with marrow-suppressive therapy.
Appropriate studies will be undertaken in patients receiving combination
antiretroviral therapy, when indicated
• No history of allergic reaction attributed to compounds of similar chemical or
biologic composition to the agents used in this study
• No concurrent treatment on another clinical trial; supportive care trials or
non-therapeutic trials (e.g., quality of life) are allowed
• No prior malignancy except for: adequately treated basal or squamous cell skin cancer,
in situ cervical cancer, adequately treated stage I or II cancer from which the
patient is currently in complete remission, or any other cancer from which the patient
has been disease free for five years. Patients with localized prostate cancer who are
being followed by an active surveillance program are also eligible
• Step 2 Patient Registration Eligibility Criteria
• Patients must have completed 4 or more cycles of protocol-directed chemotherapy and
DDR gene results must be available
• Step 3 Patient Registration Eligibility Criteria (only patients with a DDR gene
alteration)
• Deleterious alteration within 1 or more of 9 pre-defined DDR genes within the
pre-treatment TURBT deoxyribonucleic acid (DNA)
• Cystoscopy and imaging performed to determine stage/treatment assignment
HYPORT: A Phase I/II Study of Hypofractionated Post-operative Radiation Therapy for Head and Neck Cancer
There is a strong radiobiological and economic rationale for hypofractionated radiation
therapy in head and neck cancer. Phase 1 of the trial aims to assess the acute toxicity and
tolerability of hypofractionated radiation therapy in the post-operative setting, and to
determine the dose/fractionation for Phase 2. Phase 2 aims to establish non-inferiority of
swallowing-related quality of life and to assess the toxicity and efficacy of
hypofractionated radiation therapy compared to conventionally fractionated radiation therapy
in the post-operative setting.
Inclusion criteria will be the same for Phase I and Phase II.
1. Pathologically proven diagnosis of stage I-IVB squamous cell carcinoma of the oral
cavity, oropharynx, hypopharynx, or larynx status post gross total resection with
pathology showing one or more of the following intermediate risk factors:
• T3/4 disease (AJCC 8th edition), positive lymph node(s), close margin(s),
perineural invasion, and/or lymphovascular invasion
• Close margin(s) defined as either:
• Final patient margin of <5 mm without disease on ink OR
• Initial positive margin in the specimen regardless of the final patient
margin (e.g. if resection margin on the initial specimen is positive, final
patient margin after subsequent resections can be ≥5 mm and still be
considered close margin)
2. Age ≥18 years
3. ECOG performance status 0-2
4. Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for 90 days following completion of therapy.
Medically acceptable birth control (contraceptives) includes:
• approved hormonal contraceptives (such as birth control pills, patch or ring;
Depo-Provera, Implanon), or
• barrier methods (such as condom or diaphragm) used with a spermicide
Should a woman become pregnant or suspect she is pregnant while participating in this
study, she should inform her treating physician immediately.
A female of child-bearing potential is any woman (regardless of sexual orientation,
having undergone a tubal ligation, or remaining celibate by choice) who meets the
following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e.,
has had menses at any time in the preceding 12 consecutive months).
5. Negative serum or urine pregnancy test within 2 weeks before registration for women of
childbearing potential.
6. Ability to understand and the willingness to sign a written informed consent
Exclusion Criteria:
Phase I:
1. Distant metastasis
2. Stage I and II glottic squamous cell carcinoma
3. High risk factors following surgical resection requiring concurrent chemotherapy:
final positive margin(s) and/or extranodal extension
4. Feeding tube dependence at baseline assessment.
5. Synchronous non-skin cancer primaries outside of the oropharynx, oral cavity, larynx,
and hypopharynx except for low- and intermediate-risk prostate cancer and synchronous
well-differentiated thyroid cancer. For prostate cancer, patient should not be
receiving active treatment. For thyroid cancer, thyroid surgery may occur before or
after treatment, provided all other eligibility criteria are met.
6. Prior invasive malignancy with an expected disease-free interval of less than 3 years
7. Prior radiotherapy to the region of the study cancer that would result in overlap of
radiation fields
8. Subjects may not be receiving any other investigational agents for the treatment of
the cancer under study.
9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that, in the opinion of the
investigator, would limit compliance with study requirements
10. Subjects must not be pregnant or nursing due to the potential for congenital
abnormalities and the potential of this regimen to harm nursing infants.
11. History of severe immunosuppression, including HIV, and organ or autologous or
allogeneic stem cell transplant
Phase II:
The exclusion criteria will be the same as Phase I except for feeding tube dependence.
Patients who are feeding tube dependent are excluded from Phase I to accurately assess
treatment associated toxicity affecting swallowing and oral intake. During Phase II,
patients who are feeding tube dependent will be eligible to enroll and stratified at
randomization.
Standard Systemic Therapy With or Without Definitive Treatment in Treating Participants With Metastatic Prostate Cancer
This phase III trial studies how well standard systemic therapy with or without definitive
treatment (prostate removal surgery or radiation therapy) works in treating participants with
prostate cancer that has spread to other places in the body. Addition of prostate removal
surgery or radiation therapy to standard systemic therapy for prostate cancer may lower the
chance of the cancer growing or spreading.
• STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: All patients must have a histologically
or cytologically proven diagnosis of adenocarcinoma of the prostate. Patients with
pure small cell carcinoma* (SCC), sarcomatoid, or squamous cell carcinoma are not
eligible. (*morphology must be consistent with SCC; synaptophysin or chromogranin
positive by immunohistochemical staining is insufficient to diagnose SCC).
• STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: Patients must have an intact prostate.
No prior local therapy for prostate adenocarcinoma is allowed (e.g., brachytherapy,
high-intensity focused ultrasound [HIFU], cryotherapy, laser ablative therapies). Any
prior therapy for benign conditions, such as obstruction, are acceptable (e.g.,
transurethral resection of the prostate, greenlight laser ablation, microwave
ablation).
• STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: Patients must have evidence of
metastatic disease on technetium bone scan and computed tomography (CT) or magnetic
resonance imaging (MRI) within 42 days prior to starting standard systemic therapy.
Metastatic disease that is detected by positron emission tomography (PET) scan only
(sodium fluoride [NaF], prostate-specific membrane antigen [PSMA],
anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid [FACBC], carbon [C]11) but not
conventional imaging (technetium [Tc]99 bone scan, CT or MRI) or solitary metastases
by conventional imaging, must be confirmed histologically or cytologically.
• STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: Patients with known brain metastases
are not eligible. Brain imaging studies are not required for eligibility if the
patient has no neurologic signs or symptoms suggestive of brain metastasis. If brain
imaging studies are performed, they must be negative for disease.
• STEP 1 REGISTRATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must have received no
more than 28 weeks of standard systemic therapy (SST). SST is defined as current
National Comprehensive Cancer Network (NCCN) guidelines for metastatic prostate
cancer.
• STEP 1 REGISTRATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must not have
progressed while on SST.
• STEP 1 REGISTRATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients with oligometastatic
prostate cancer may receive metastasis directed therapy to up to four sites of disease
prior to randomization.
• STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: Patients must have a complete
physical examination and medical history within 28 days prior to registration.
• STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: Patients must have a PSA documented
prior to initiation of SST and within 28 days prior to registration. Any additional
PSAs measured while receiving SST should be recorded.
• STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: Patients must have a testosterone
lab documented within 28 days prior to randomization. Any additional testosterone labs
measured while receiving SST should be recorded as well as pretreatment initiation if
available.
• STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: No other prior malignancy is
allowed except for the following: adequately treated basal cell or squamous cell skin
cancer, adequately treated stage 0, I or II cancer from which the patient is currently
in complete remission, or any other cancer from which the patient has been disease
free for three years.
• STEP 1 REGISTRATION: SPECIMEN SUBMISSION CRITERIA: Patients must be offered the
opportunity to participate in translational medicine studies and specimen banking for
future studies.
• STEP 1 REGISTRATION: QUALITY OF LIFE CRITERIA: Patients who can complete
Patient-Reported Outcome instruments in English, Spanish or French, must participate
in the quality of life studies.
• STEP 1 REGISTRATION: REGULATORY CRITERIA: Patients must be informed of the
investigational nature of this study and must sign and give written informed consent
in accordance with institutional and federal guidelines.
• STEP 2 RANDOMIZATION: DISEASE-RELATED CRITERIA: As a part of the OPEN registration
process the treating institution's identity is provided in order to ensure that the
current (within 365 days) date of institutional review board approval for this study
has been entered in the system.
• STEP 2 RANDOMIZATION: DISEASE-RELATED CRITERIA: Patients must have no evidence of
disease progression during the 28 weeks of SST by PSA measure, bone scan and CT or MRI
or symptomatic deterioration (as defined by physician discretion) within 28 days prior
to randomization.
• STEP 2 RANDOMIZATION: DISEASE-RELATED CRITERIA: Patients must have consultation with a
urologist and have surgically resectable disease regardless of definitive treatment
intent or randomization.
• STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must have received
between 22 and 28 weeks of SST as measured from the date of first hormonal therapy or
surgical castration. SST is defined by current NCCN guidelines for metastatic prostate
cancer.
• STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must not be planning
to receive docetaxel after randomization.
• STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Any toxicities from SST must
have resolved to =< grade 1 (Common Terminology Criteria for Adverse Events [CTCAE]
version 5.0) prior to randomization.
• STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients may have received
elective metastasis directed therapy to oligometastatic sites (=< 4 sites). All
treatment must be completed prior to randomization.
• STEP 2 RANDOMIZATION: CLINICAL/LABORATORY CRITERIA: Patients must have a PSA performed
within 28 days prior to randomization.
• STEP 2 RANDOMIZATION: CLINICAL/LABORATORY CRITERIA: Patients must have a testosterone
< 50 ng/dL within 28 days prior to randomization.
• STEP 2 RANDOMIZATION: CLINICAL/LABORATORY CRITERIA: Patients must have a Zubrod
performance status of 0 ? 1 within 28 days prior to randomization.
Stage IV Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8, Castration Levels of Testosterone, Metastatic Prostatic Adenocarcinoma
UT Southwestern; Parkland Health & Hospital System
Efficacy and Safety of Olaparib (MK-7339) in Participants With Previously Treated, Homologous Recombination Repair Mutation (HRRm) or Homologous Recombination Deficiency (HRD) Positive Advanced Cancer (MK-7339-002 / LYNK-002)
This study will evaluate the efficacy and safety of olaparib (MK-7339) monotherapy in
participants with multiple types of advanced cancer (unresectable and/or metastatic) that: 1)
have progressed or been intolerant to standard of care therapy; and 2) are positive for
homologous recombination repair mutation (HRRm) or homologous recombination deficiency (HRD).
• Has a histologically- or cytologically-confirmed advanced (metastatic and/or
unresectable) solid tumor (except breast or ovarian cancers whose tumor has a germline
or somatic BRCA mutation) that is not eligible for curative treatment and for which
standard of care therapy has failed. Participants must have progressed on or be
intolerant to standard of care therapies that are known to provide clinical benefit.
There is no limit on the number of prior treatment regimens.
• Has either centrally-confirmed known or suspected deleterious mutations in at least 1
of the genes involved in HRR or centrally-confirmed HRD.
• For participants receiving prior platinum (cisplatin, carboplatin, or oxaliplatin
either as monotherapy or in combination) for advanced (metastatic and/or unresectable)
solid tumor, have no evidence of disease progression during the platinum chemotherapy.
• Has measurable disease per RECIST 1.1 or PCWG-modified RECIST 1.1 as assessed by the
local site Investigator/radiology and confirmed by BICR.
• Is able to provide a newly obtained core or excisional biopsy of a tumor lesion or
either an archival formalin-fixed paraffin embedded (FFPE) tumor tissue block or
slides.
• Has a life expectancy of at least 3 months.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1,
as assessed within 3 days of treatment initiation.
• Male participants must agree to use contraception during the treatment period and for
at least 90 days (3 months) after the last dose of study treatment and refrain from
donating sperm during this period.
• Female participants must not be pregnant or breastfeeding. Additionally, female
participants must either not be a woman of childbearing potential (WOCBP) or, if a
WOCBP, agree to use contraception during the treatment period and for at least 30 days
(1 month) after the last dose of study treatment.
• Has adequate organ function.
Exclusion Criteria:
• Has a known additional malignancy that is progressing or has required active treatment
in the last 5 years. Note: Participants with basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, ductal carcinoma in situ, or cervical carcinoma
in situ that has undergone potentially curative therapy are not excluded.
• Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features
suggestive of MDS/AML.
• Has known central nervous system (CNS) metastases and/or carcinomatous meningitis.
Note: Participants with previously treated brain metastases may participate if
radiologically stable, clinically stable, and without requirement for steroid
treatment for at least 14 days prior to the first dose of study treatment.
• Has received colony-stimulating factors (e.g., granulocyte colony-stimulating factor
[G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF] or recombinant
erythropoietin) within 28 days prior to the first dose of study treatment.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has known active hepatitis infection (i.e., Hepatitis B or C).
• Is unable to swallow orally administered medication or has a gastrointestinal disorder
affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).
• Has received prior therapy with olaparib or with any other polyadenosine 5'
diphosphoribose (poly[ADP ribose]) polymerization (PARP) inhibitor.
• Has a known hypersensitivity to the components or excipients in olaparib.
• Has received previous allogenic bone-marrow transplant or double umbilical cord
transplantation (dUCBT).
• Has received a whole blood transfusion in the last 120 days prior to entry to the
study. Packed red blood cells and platelet transfusions are acceptable if not
performed within 28 days of the first dose of study treatment.
Enfortumab Vedotin and Pembrolizumab vs. Chemotherapy Alone in Untreated Locally Advanced or Metastatic Urothelial Cancer (EV-302)
This study is being done to see how well two drugs (enfortumab vedotin and pembrolizumab)
work together to treat patients with urothelial cancer. The study will compare these drugs to
other drugs that are usually used to treat this cancer (standard of care). The patients in
this study will have cancer that has spread from their urinary system to other parts of their
body.
• Histologically documented, unresectable locally advanced or metastatic urothelial
carcinoma
• Measurable disease by investigator assessment according to RECIST v1.1
• Participants with prior definitive radiation therapy must have measurable disease
per RECIST v1.1 that is outside the radiation field or has demonstrated
unequivocal progression since completion of radiation therapy
• Participants must not have received prior systemic therapy for locally advanced or
metastatic urothelial carcinoma with the following exceptions:
• Participants that received neoadjuvant chemotherapy with recurrence >12 months
from completion of therapy are permitted
• Participants that received adjuvant chemotherapy following cystectomy with
recurrence >12 months from completion of therapy are permitted
• Must be considered eligible to receive cisplatin- or carboplatin-containing
chemotherapy, in the investigator's judgment
• Archival tumor tissue comprising muscle-invasive urothelial carcinoma or a biopsy of
metastatic urothelial carcinoma must be provided for PD-L1 testing prior to
randomization
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2
• Adequate hematologic and organ function
Exclusion Criteria
• Previously received enfortumab vedotin or other monomethyl auristatin E (MMAE)-based
antibody-drug conjugate (ADCs)
• Received prior treatment with a programmed cell death ligand-1 (PD-(L)-1) inhibitor
for any malignancy, including earlier stage urothelial cancer (UC), defined as a PD-1
inhibitor or PD-L1 inhibitor
• Received prior treatment with an agent directed to another stimulatory or co
inhibitory T-cell receptor
• Received anti-cancer treatment with chemotherapy, biologics, or investigational agents
not otherwise prohibited by exclusion criterion 1-3 that is not completed 4 weeks
prior to first dose of study treatment
• Uncontrolled diabetes
• Estimated life expectancy of less than 12 weeks
• Active central nervous system (CNS) metastases
• Ongoing clinically significant toxicity associated with prior treatment that has not
resolved to ≤ Grade 1 or returned to baseline
• Currently receiving systemic antimicrobial treatment for active infection (viral,
bacterial, or fungal) at the time of randomization. Routine antimicrobial prophylaxis
is permitted.
• Known active hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV)
infection.
• History of another invasive malignancy within 3 years before the first dose of study
drug, or any evidence of residual disease from a previously diagnosed malignancy
• Documented history of a cerebral vascular event (stroke or transient ischemic attack),
unstable angina, myocardial infarction, or cardiac symptoms consistent with New York
Heart Association (NYHA) Class IV within 6 months prior to randomization
• Receipt of radiotherapy within 2 weeks prior to randomization
• Received major surgery (defined as requiring general anesthesia and >24 hour inpatient
hospitalization) within 4 weeks prior to randomization
• Known severe (≥ Grade 3) hypersensitivity to any enfortumab vedotin excipient
contained in the drug formulation of enfortumab vedotin
• Active keratitis or corneal ulcerations
• History of autoimmune disease that has required systemic treatment in the past 2 years
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced
pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
chest computed tomography (CT) scan
• Prior allogeneic stem cell or solid organ transplant
• Received a live attenuated vaccine within 30 days prior to randomization
The goal of this research is to examine the ability of Gallium-68 (68Ga) Prostate-Specific
Membrane Antigen-11 (PSMA-11) positron emission tomography/computed tomography (PET/CT) to
detect sites of recurrent prostate cancer in patients with biochemical recurrence previously
treated with radical prostatectomy (RP) or external beam radiation (EBRT) and to assess
treatment response to subsequent salvage therapy.
• Patients with suspected BCR of prostate cancer following initial treatment with either
prostatectomy or definitive EBRT of the prostate or patients with known metastatic
prostate cancer who have failed systemic therapy.
• Patients being considered for salvage therapy.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0-3.
• Patients must be medically stable as judged by the patient's physician.
• Patients must be able to lie still for 20-40 minutes for the PET/CT scans.
• Ability to understand and the willingness to sign a written informed consent.
• Patients with BCR and no known lesions should not be on antiandrogen therapy at the
time of scans. Patients with known metastases who are currently being treated with
anti-androgen therapy may remain on this medication.
Exclusion Criteria:
• Patients who have or have had a biopsy proven concurrent other malignancy, excluding
skin cancers.
• Patients may not weigh more than the maximum weight limit for the PET /CT scanner
table (> 200 kg or 440 pounds).
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to 68Ga PSMA-11. Furosemide will not be administered to patients with
known allergy.
• Patients must not be claustrophobic.
• Written informed consent in accordance with federal, local, and institutional
guidelines. The patient must provide informed consent prior to the first screening
procedure.
• Previously treated (up to three prior lines of therapy), histologically proven
advanced squamous NSCLC.
• No prior treatment with EGFR inhibitors, IMIDs (eg, thalidomide, lenalidomide), or
anti-TNF antibodies.
• No treatment with systemic glucocorticoids within 3 weeks of initiation of study
therapy (topical and inhaled glucocorticoids are permitted).
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ and marrow function as defined below:
• absolute neutrophil count ≥ 1,000/μL
• platelets ≥ 50,000/μl
• total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SPGT) ≤ 2.5 X institutional upper limit of normal
• CrCl ≥ 45 ml/min
• For both male and female patients, effective methods of contraception must be used
throughout the study and for 3 months following the last dose of study treatment.
• Adequate archival tissue (5-10 slides) for correlative studies.
• Subject must have measurable disease per RECIST 1.1
Exclusion Criteria:
• Chemotherapy, radiotherapy, or other cancer therapy within two weeks prior to starting
study treatment. Subjects must have recovered from prior treatment-related to
toxicities to grade 1 or baseline (excluding alopecia and clinically stable toxicities
requiring ongoing medical management, such as hypothyroidism from prior immune
checkpoint inhibitor treatment).
• Subjects may not be receiving any other investigational agents for the treatment of
the cancer under study.
• Symptomatic brain metastases or brain metastases requiring escalating doses of
corticosteroids
• History of hypersensitivity or allergic reactions attributed to afatinib or
prednisone.
• Uncontrolled intercurrent illness including but not limited to poorly controlled
diabetes (which may worsen in setting of chronic prednisone therapy), symptomatic
congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric
illness/social situations that, in the opinion of the investigator, would limit
compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital
abnormalities and the potential of this regimen to harm nursing infants.
Drug: Afatinib + Prednisone
Lung/Thoracic, Advanced Squamous Non Small Cell Lung Cancer
UT Southwestern; Parkland Health & Hospital System
Study of Venetoclax in Combination With Carfilzomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma (MM)
A Phase 2, open-label, dose escalation study to evaluate the safety and efficacy of
venetoclax in combination with carfilzomib-dexamethasone (Kd) in participants with relapsed
or refractory MM and have received 1 to 3 prior lines of therapy.
Part 4 of this study is currently enrolling.
• Eastern Collaborative Oncology Group (ECOG) performance score of less than or equal to
2.
• Documented relapsed or progressive Multiple Myeloma (MM) on or after any regimen or is
refractory to the most recent line of therapy.
• Positive for translocation t(11;14) as determined by an analytically validated
Fluorescent In Situ Hybridization (FISH) assay per central laboratory testing.
• Received prior treatment with at least 1 prior line of therapy for MM.
• Measurable disease on Screening per International Myeloma Working Group (IMWG)
criteria.
• Meets absolute neutrophil count, platelet count, hemoglobin, liver and kidney function
laboratory values within 2 weeks prior to first dose of study drug.
Exclusion Criteria:
• Has a pre-existing condition that is contraindicated including.
• Non-secretory or oligo-secretory MM
• Active plasma cell leukemia.
• Waldenström's macroglobulinemia.
• Primary amyloidosis.
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein,
and skin changes).
• Active hepatitis B or C infection based on screening blood testing.
• Known active Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
infection.
• Significant cardiovascular disease.
• Major surgery within 4 weeks prior to first dose.
• Acute infections requiring antibiotic, antifungal or antiviral therapy within14
days prior to first dose.
• Peripheral neuropathy ≥ Grade 3 or ≥ Grade 2 with pain within 2 weeks prior to
first dose.
• Uncontrolled diabetes or uncontrolled hypertension within 14 days prior to first
dose.
• Any other medical condition that, in the opinion of the Investigator, would
adversely affect the participant's participation in the study.
• History of other active malignancies, including myelodysplastic syndrome (MDS), within
the past 3 years prior to study entry Other protocol defined inclusion/exclusion
criteria could apply
High Flow Nasal Cannula (HFNC) Initiation Flow Rate Study
The investigators propose an open label, non-blinded, single center randomized controlled
feasibility study to find the optimal initial HFNC flow rate in children less than 12 months
old with clinically diagnosed moderate to severe bronchiolitis. This feasibility study is
projected over December 2020 to April 2023. The study is consisted of 3 arms, comparing HFNC
therapy at 1 L/kg/min, 1.5 L/kg/min, and 2 L/kg/min (20 L/min max). Moderate to severe
bronchiolitis is defined clinician's assessment for the need for ICU level of care.
The primary outcome is treatment response to HFNC therapy defined by RDAI/Respiratory
Assessment Change Score (RACS) ≥ 4 at 4 hours of therapy. Secondary outcome measures comprise
of treatment failure requiring an escalation of care during the first 24 hours of HFNC
therapy, duration of HFNC and simple nasal cannula therapy, duration of simple nasal cannula
therapy, hospital and PICU length of stay (LOS), time to treatment failure, and adverse
events.
• Patients less than 12 months of age
• Clinical signs of moderate to severe bronchiolitis defined by American Academy of
Pediatrics
• Requires ICU level of care by clinicians' discretion
• Requiring HFNC support
Exclusion Criteria:
• Infants who required immediate need for respiratory support such as non-invasive
positive pressure ventilation (NIPPV) or invasive ventilation
• Congenital heart disease,
• Immunocompromised state
• Upper airway obstruction
• Chronic lung disease
• Bronchopulmonary dysplasia,
• Home oxygen therapy requirement
• Acute trauma patients
• Baseline craniofacial malformations
• Admitted to the neonatal or cardiac ICUs
• Patients who are admitted to the floor
Other: Initial Flow Rate
Bronchiolitis
Bronchiolitis, HFNC, High Flow Nasal Cannula, Infants
Pragmatic Evaluation of Events And Benefits of Lipid-lowering in Older Adults (PREVENTABLE)
PREVENTABLE is a multi-center, randomized, parallel group, placebo-controlled superiority
study. Participants will be randomized 1:1 to atorvastatin 40 mg or placebo. This large study
conducted in community-dwelling older adults without cardiovascular disease (CVD) or dementia
will demonstrate the benefit of statins for reducing the primary composite of death,
dementia, and persistent disability and secondary composites including mild cognitive
impairment (MCI) and cardiovascular events.
• Community-dwelling adults
• Age ≥75 years
• English or Spanish as primary language
Exclusion Criteria:
• Clinically evident cardiovascular disease defined as prior myocardial Infarction (MI),
prior stroke, prior revascularization procedure, or a secondary prevention indication
for a statin (clinician determined)
• Hospitalization for a primary diagnosis of heart failure in the prior 12 months (Note:
History of heart failure in the absence of recent hospitalization or clinically
evident cardiovascular disease is not an exclusion)
• Dementia (clinically evident or previously diagnosed)
• Dependence in any Katz Basic Activities of Daily Living [ADL] (with the exception of
urinary or bowel continence)
• Severe hearing impairment (preventing phone follow up)
• Unable to talk (preventing phone follow up)
• Severe visual impairment (preventing cognitive testing)
• Statin use in the past year or for longer than 5 years previously (participant
reported)
• Ineligible to take atorvastatin 40 mg (clinician determined)
• Documented intolerance to statins
• Active Liver Disease
• Long-term use of daily colchicine, verapamil at any dose, or diltiazem at a dose
>240mg/day.
A Study to Evaluate the Effectiveness and Safety of CAEL-101 in Patients With Mayo Stage IIIa AL Amyloidosis
AL (or light chain) amyloidosis begins in the bone marrow where abnormal proteins misfold and
create free light chains that cannot be broken down. These free light chains bind together to
form amyloid fibrils that build up in the extracellular space of organs, affecting the
kidneys, heart, liver, spleen, nervous system and digestive tract.
The primary purpose of this study is to determine if CAEL-101 improves the overall survival
in Patients with cardiac AL Amyloidosis.
• Each patient must meet the following criteria to be enrolled in this study.
1. Be able to and provide written informed consent and be willing and able to comply
with all study procedures
2. Adult, 18 years and older
3. AL amyloidosis Mayo stage IIIa based on the 2013 European Modification of the
2004 Standard Mayo Clinic Staging in patients with advanced cardiac involvement
at the time of Screening
4. Measurable hematologic disease at Screening as defined by at least one of the
following:
1. Involved/Uninvolved Free Light Chain Difference (dFLC) > 4 mg/dL or
2. Involved Free Light Chain (iFLC) > 4 mg/dL with abnormal ratio or
3. Serum Protein Electrophoresis (SPEP) m-spike > 0.5 g/dL
5. Histopathological diagnosis of amyloidosis AND confirmation of AL derived amyloid
deposits by at least one of the following:
1. Immunohistochemistry or
2. Mass spectrometry or
3. Characteristic electron microscopy appearance
6. Cardiac involvement as defined by:
a. Documented clinical signs and symptoms supportive of a diagnosis of heart
failure in the setting of a confirmed diagnosis of AL amyloidosis in the absence
of an alternative explanation for heart failure AND b. At least one of the
following: i. Endomyocardial biopsy demonstrating AL cardiac amyloidosis or
ii. Echocardiogram demonstrating a mean left ventricular wall thickness
(calculated as [IVSd+LPWd]/2) of > 12 mm at diastole in the absence of other
causes (e.g., severe hypertension, aortic stenosis), which would adequately
explain the degree of wall thickening or
iii. Cardiac MRI with gadolinium contrast agent diagnostic or cardiac amyloidosis
7. Planned first-line treatment for plasma cell dyscrasia is a CyBorD-based regimen
administered as Standard of Care (SoC)
8. Adequate bone marrow reserve and hepatic function as demonstrated by:
1. Absolute neutrophil count ≥ 1.0 x 109/L
2. Platelet count ≥ 75 x 109/L
3. Hemoglobin ≥ 9 g/dL
4. Total direct bilirubin ≤ 2 times the upper limit of normal (x ULN) unless
due to Gilbert's syndrome.
5. Aspartate aminotransferase (AST) ≤ 3 x ULN
6. Alanine aminotransferase (ALT) ≤ 3 x ULN
7. Alkaline phosphatase (ALP) ≤ 5 x ULN (except for patients with hepatomegaly
and isozymes specific to liver, rather than bone)
9. Women of childbearing potential (WOCBP) must have a negative pregnancy test
during Screening and must agree to use highly effective physician approved
contraception from Screening to at least 5 months following the last study drug
administration or 12 months following the last dose of her PCD therapy, whichever
is longer
10. Men must be surgically sterile or must agree to use effective physician approved
contraception and refrain from donating sperm from Screening to at least 5 months
following the last study drug administration or 12 months following the last dose
of his PCD therapy, whichever is longer
Exclusion Criteria:
• Patients who meet any of the following criteria will not be permitted entry to the
study.
1. Have any other form of amyloidosis other than AL amyloidosis
2. Received prior therapy for AL amyloidosis or multiple myeloma. A maximum exposure
of 2 weeks of a CyBorD-based PCD treatment after screening laboratory samples are
obtained and prior to randomization is allowed.
3. Has POEMS syndrome or multiple myeloma defined as clonal bone marrow plasma cells
> 10% or biopsy-proven bony or extramedullary plasmacytoma AND any one or more of
the following CRAB features:
a. Evidence of end organ damage that can be attributed to the underlying plasma
cell proliferative disorder, specifically:
i. Hypercalcemia: serum calcium > 0.25 mmol/L (> 1mg/dL) higher than the ULN or >
2.75 mmol/L (> 11mg/dL)
ii. Renal insufficiency: creatinine clearance < 40 mL per minute or serum
creatinine > 177mol/L (> 2mg/dL)
iii. Anemia: hemoglobin value of > 20g/L below the lowest limit of normal, or a
hemoglobin value < 100g/L
iv. Bone lesions: one or more osteolytic lesion on skeletal radiography, CT, or
PET/CT. If bone marrow has < 10% clonal plasma cells, more than one bone lesion
is required to distinguish from solitary plasmacytoma with minimal marrow
involvement
OR
b. Any one of the following biomarkers of malignancy:
i. 60% or greater clonal plasma cells on bone marrow examination
ii. More than one focal lesion on MRI that is at least 5mm or greater in size
4. Have supine systolic blood pressure < 90 mmHg or symptomatic orthostatic
hypotension, defined as a decrease in systolic blood pressure upon standing of >
30 mmHg despite medical management (e.g., midodrine, fludrocortisones) in the
absence of volume depletion
5. Taking prednisone or its equivalent > 10 mg/day
6. Taking doxycycline
7. Receiving dialysis
8. Planned stem cell transplant during the first 6 months of protocol therapy. Stem
cell collection during the protocol therapy is permitted.
9. Have had myocardial infarction, uncontrolled angina, severe uncontrolled
ventricular arrhythmias within 6 months prior to screening or percutaneous
cardiac intervention with recent stent or coronary artery bypass grafting within
4 months prior to screening. Exacerbation of chronic condition or new acute
condition will require discussion and approval by the Medical Monitor.
10. Left Ventricular Ejection Fraction (LVEF) is < 40% by echocardiogram at Screening
11. Have severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area
< 1.0 cm2) or severe congenital heart disease
12. Have history of sustained ventricular tachycardia or aborted ventricular
fibrillation or a history of atrioventricular nodal or sinoatrial nodal
dysfunction for which a pacemaker/implantable cardioverter-defibrillator (ICD) is
indicated but not placed. (Participants who do have a pacemaker or ICD are
allowed in the study.)
13. QT corrected by Fridericia (QTcF) is > 550 msec. Participants who have a
pacemaker may be included regardless of calculated QTc interval.
14. There is evidence of acute ischemia or active conduction system abnormalities
with the exception of any of the following:
1. First degree Atrioventricular (AV)-block
2. Second degree AV-block Type 1 (Mobitz Type 1/Wenckebach type)
3. Right or left bundle branch block
4. Atrial fibrillation with a controlled ventricular rate. (An uncontrolled
ventricular rate [i.e., > 110 beats per minute] determined by an average of
three beats in lead II or representative beats in lead II is not allowed)
15. Have had major surgery within 4 weeks of randomization or is planning major
surgery during the study. Patients with surgical procedures conducted under local
anesthesia may participate
16. There is active malignancy (including lymphoma) with the exception of any of the
following:
1. Adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ
cervical cancer
2. Adequately treated stage I cancer from which the patient is currently in
remission and has been in remission for > 2 years
3. Low-risk prostate cancer with Gleason score < 7 and prostate-specific
antigen < 10 mg/mL
4. Other localized and/or low risk malignancies may be permitted with Medical
Monitor approval.
17. Have received an investigational drug/device in another clinical investigational
study within 60 days before Screening
18. Hypersensitivity to the study drug
19. Have received a live vaccine within 4 weeks prior to first dose of CyBorD
20. Women who are breast feeding
21. Have any other medical, social or psychological factors that could affect the
patient's safety or ability to consent personally or comply with study
procedures.
1. Have histologically confirmed advanced or metastatic castration-resistant prostate
cancer, bladder cancer, melanoma, non-small cell lung cancer, pancreatic cancer,
colorectal cancer, gastric cancer, esophageal cancer, ovarian cancer, and head neck
squamous cell carcinoma.
Or,
Have histologically confirmed metastatic pancreatic adenocarcinoma. Recurrent
unresectable pancreatic cancer is acceptable as long as the treatment is first-line.
2. Have not received any approved chemotherapy, except in the adjuvant setting.
Exclusion Criteria:
1. Subject was using immunosuppressive medications within 14 days before Screening with
the exception of topical (intranasal, inhaled, and local injection), systemic
(prednisone equivalent 10 mg/day or less), or as needed for hypersensitivity reactions
such as computed tomography (CT) scan premedication.
2. Subject has active infections or other serious underlying significant medical illness,
abnormal and clinically significant laboratory findings or psychiatric illness/social
situation.
3. Subject is using a pacemaker, implantable cardiac defibrillator, neurostimulator,
cochlear implants, cochlear implants, or other electronic medical equipment.
4. Subject has documented immunodeficiency or organ transplant.
5. Subject has an untreated central nervous system disease, leptomeningeal disease or
cord compression.
6. Subject has a history, or presence, of significant cardiovascular diseases; including
uncontrolled hypertension, clinically relevant cardiac arrhythmia, unstable angina or
myocardial infarction within 6 months before randomization, congestive heart failure >
New York Heart Association Class II, severe peripheral vascular disease, corrected QT
(QTc) prolongation >470 msec, clinically significant pericardial effusion.
7. Subject has a history or presence of documented inflammatory bowel disease.
8. Subject is known to be positive for human immunodeficiency virus infection.
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