Search Results
within category "Kidney & Urinary System"
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.
Phase 1 Dose-escalating Study of MM-398 (Irinotecan Sucrosofate Liposome Injection) Plus Intravenous Cyclophosphamide in Recurrent or Refractory Pediatric Solid Tumors
This is a Phase 1 study of the combination of two drugs: MM-398 and Cyclophosphamide. The
goal is to find the highest dose of MM-398 that can be given safely when it is used together
with the chemotherapy drug Cyclophosphamide.
• Histologically or cytologically-confirmed Ewing sarcoma, rhabdomyosarcoma,
neuroblastoma, or osteosarcoma
• Disease progression after prior therapy in locally advanced or metastatic setting
• Measurable or evaluable disease based on the Response Evaluation Criteria in Solid
Tumors (RECIST v1.1) criteria
• Age 12 months to <21 years
• Adequate bone marrow reserves, hepatic function, and renal function
• Recovered from effects of any prior surgery or cancer therapy
• Patients 18 years or older will provide written consent. A parent or legal guardian of
a patient <18 years of age will provide informed consent and patients 11 to 18 years
of age will provide written assent or as per participating institutional policy.
Exclusion Criteria:
• Clinically significant gastrointestinal disorders
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled
blood pressure
• Active infection or unexplained fever
• Known hypersensitivity to any of the components of MM-398 or other liposomal products
• Recent Investigational therapy
• Pregnant or breast feeding; females of child-bearing potential must test negative for
pregnancy at the time of enrollment
Drug: MM-398 (Irinotecan Sucrosofate Liposome Injection) plus cyclophosphamide
Neuroblastoma, Sarcoma, Ewing Sarcoma, Mycosis Fungoides, Rhabdomyosarcoma, Osteosarcoma, Recurrent or Refractory Solid Tumors, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Hodgkins Lymphoma, Kaposis sarcoma, Other Hematopoietic, Small Intestine, Soft Tissue
CAN-Stim Compared to SNS in Treatment of Urinary Urgency Incontinence With Wireless Neuromodulation Technology (PROTECT)
This is a prospective, randomized, controlled, multi-center, study in which 150 evaluable
subjects will be randomized 1:1 to receive either a Protect CAN-Stim or SNS InterStim®
system. Subjects from both groups will immediately start with therapy. The primary endpoint
is a ≥ 50% reduction in number of incontinence episodes associated with urgency at the
3-month visit, with additional measurements assessed at 14 days, 1, 6, 9 and 12-months.
• Diagnosis of overactive bladder with urgency urinary incontinence or mixed
incontinence (urge and stress) with predominate urge, as confirmed by the MESA
questionnaire;
• Women and men ≥ 18 years of age;
• Women of child-bearing age willing to practice birth control;
• At least 4 incontinent episodes associated with urgency on a 3-day voiding diary;
• At least 10 voids per day;
• Average urgency score of at least 2 as measured with IUSS on a 3-day voiding diary;
• Self-reported bladder symptoms present > 6 months;
• Documented failure of an adequate trial of first and second line therapy;
• Off all antimuscarinics and beta-3 adrenergic agonists for at least 2 weeks prior to
enrollment;
• If on Tricyclic antidepressants, dosage must be stabilized for at least 3 months;
• Have no active urethral obstruction/stricture, bladder calculi or bladder tumor based
on medical history;
• Normal upper urinary tract function based on medical history;
• Based on the medical opinion of the Investigator, there is no evidence of anatomic
abnormalities that could jeopardize the placement of the device or pose a hazard to
the subject;
• Based on the medical opinion of the Investigator, subject is willing and able to
operate the patient programmer, recharging equipment, diary and has the ability to
undergo study assessments and provide accurate responses;
• Based on the medical opinion of the Investigator, subject is a good surgical subject
for the implant procedure;
• Capable of giving informed consent;
• Capable and willing to follow all study related procedures.
Exclusion Criteria:
• An active implantable electronic device regardless of whether stimulation is ON or
OFF;
• Pregnant as confirmed by a urine pregnancy test or plan to become pregnant during the
following 12 months period;
• Primary complaint of stress urinary incontinence;
• Less than 1 year post-partum and/or are breast-feeding;
• Neurogenic bladder (i.e. Multiple sclerosis, Parkinson's, Spinal Cord Injury);
• Patients with spinal hardware that would limit access to the sacrum;
• Botox use in bladder or pelvic floor muscles in the past nine months;
• Have a post-void residual urine volume >150 cc at baseline;
• Current urinary tract infection (UTI);
• Previous treatment with sacral neuromodulation;
• Previous treatment with percutaneous tibial nerve stimulation, pelvic floor muscle
stimulation, or biofeedback within the past 60 days;
• Conditions requiring Magnetic Resonance Imaging (MRI) evaluation or diathermy
procedures;
• Inability to operate the CAN-Stim System or InterStim System;
• Diabetes with peripheral nerve compromise or severe uncontrolled diabetes (HbA1C 8.5
or greater);
• History of coagulopathy or bleeding disorder;
• History of pelvic pain as primary diagnosis (VAS score of > 4) at baseline;
• Anatomical restrictions such that device placement is not possible;
• Are currently participating or have participated within the past 30 days in any
clinical investigation involving or impacting urinary or renal function;
• Have a life expectancy of less than 1 year;
• Cannot independently comprehend and complete the questionnaires and diaries;
• Deemed unsuitable for enrollment by the investigator based on history or physical
examination (including bleeding disorders or anticoagulant medications, and peripheral
neuropathy);
• Dependent on wearable, transcutaneous, or other therapeutic medical device (examples:
glucose monitor, TENS) for treatment of a disease or disorder.
A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001) (LIBRETTO-001)
This is an open-label, first-in-human study designed to evaluate the safety, tolerability,
pharmacokinetics (PK) and preliminary anti-tumor activity of selpercatinib (also known as
LOXO-292) administered orally to participants with advanced solid tumors, including
rearranged during transfection (RET)-fusion-positive solid tumors, medullary thyroid cancer
(MTC) and other tumors with RET activation.
For Phase 1:
• Participants with a locally advanced or metastatic solid tumor that:
• Has progressed on or is intolerant to standard therapy, or
• For which no standard therapy exists, or in the opinion of the Investigator, are not
candidates for or would be unlikely to tolerate or derive significant clinical benefit
from standard therapy, or
• Decline standard therapy
• Prior multikinase inhibitors (MKIs) with anti-RET activity are allowed
• A RET gene alteration is not required initially. Once adequate PK exposure is
achieved, evidence of RET gene alteration in tumor and/or blood is required as
identified through molecular assays, as performed for clinical evaluation
• Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as
appropriate to tumor type
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 or Lansky Performance
Score (LPS) greater than or equal to (≥) 40 percent (%) (age less than [<] 16 years)
with no sudden deterioration 2 weeks prior to the first dose of study treatment
• Adequate hematologic, hepatic and renal function
• Life expectancy of at least 3 months
For Phase 2: As for phase 1 with the following modifications:
• For Cohort 1: Participants must have received prior standard therapy appropriate for
their tumor type and stage of disease, or in the opinion of the Investigator, would be
unlikely to tolerate or derive clinical benefit from appropriate standard of care
therapy
• Cohorts 1 and 2:
• Enrollment will be restricted to participants with evidence of a RET gene
alteration in tumor
• At least one measurable lesion as defined by RECIST 1.1 or RANO, as appropriate
to tumor type and not previously irradiated
• Cohorts 3 and 4: Enrollment closed
• Cohort 5:
• Cohorts 1-4 without measurable disease
• MCT not meeting the requirements for Cohorts 3 or 4
• MTC syndrome spectrum cancers (e.g., MTC, pheochromocytoma), cancers with
neuroendocrine features/differentiation, or poorly differentiated thyroid cancers
with other RET alteration/activation may be allowed with prior Sponsor approval
• cfDNA positive for a RET gene alteration not known to be present in a tumor
sample
• Cohort 6: Participants who otherwise are eligible for Cohorts 1, 2 or 5 who
discontinued another RET inhibitor may be eligible with prior Sponsor approval
• Cohort 7: Participants with a histologically confirmed stage IB-IIIA NSCLC and a RET
fusion; determined to be medically operable and tumor deemed resectable by a thoracic
surgical oncologist, without prior systemic treatment for NSCLC
Key Exclusion Criteria (Phase 1 and Phase 2):
• Phase 2 Cohorts 1 and 2: an additional known oncogenic driver
• Cohorts 3 and 4: Enrollment closed
• Cohorts 1, 2 and 5: prior treatment with a selective RET inhibitor Notes: Participants
otherwise eligible for Cohorts 1, 2, and 5 who discontinued another selective RET
inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor approval
• Investigational agent or anticancer therapy (including chemotherapy, biologic therapy,
immunotherapy, anticancer Chinese medicine or other anticancer herbal remedy) within 5
half-lives or 2 weeks (whichever is shorter) prior to planned start of LOXO-292
(selpercatinib). In addition, no concurrent investigational anti-cancer therapy is
permitted Note: Potential exception for this exclusion criterion will require a valid
scientific justification and approval from the Sponsor
• Major surgery (excluding placement of vascular access) within 2 weeks prior to planned
start of LOXO-292 (selpercatinib)
• Radiotherapy with a limited field of radiation for palliation within 1 week of planned
start of LOXO-292 (selpercatinib), with the exception of participants receiving
radiation to more than 30% of the bone marrow or with a wide field of radiation, which
must be completed at least 4 weeks prior to the first dose of study treatment
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria
for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment with the
exception of alopecia and Grade 2, prior platinum-therapy related neuropathy
• Symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or untreated
spinal cord compression. Participants are eligible if neurological symptoms and CNS
imaging are stable and steroid dose is stable for 14 days prior to the first dose of
LOXO-292 (selpercatinib) and no CNS surgery or radiation has been performed for 28
days, 14 days if stereotactic radiosurgery (SRS)
• Clinically significant active cardiovascular disease or history of myocardial
infarction within 6 months prior to planned start of LOXO-292 (selpercatinib) or
prolongation of the QT interval corrected (QTcF) greater than (>) 470 milliseconds
(msec)
• Participants with implanted pacemakers may enter the study without meeting QTc
criteria due to nonevaluable measurement if it is possible to monitor for QT
changes.
• Participants with bundle branch block may be considered for study entry if QTc is
appropriate by a formula other than Fridericia's and if it is possible to monitor
for QT changes.
• Required treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or
inducers and certain prohibited concomitant medications
• Phase 2 Cohort 7 (neoadjuvant treatment): Participant must not have received prior
systemic therapy for NSCLC.
Drug: LOXO-292
Lymphoma, Non-Small Cell Lung Cancer, Colon Cancer, Medullary Thyroid Cancer, Any Solid Tumor, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Stomach, Thyroid, Urinary Bladder, Hodgkins Lymphoma, Small Intestine, Soft Tissue
LOXO-292, KIF5B-RET, M918T, CCDC6-RET, RET-PTC1, NCOA4-RET, RET-PTC, RET-PTC3, RET-PTC4, PRKAR1A-RET, RET-PTC2, GOLGA5-RET, RET-PTC5, ERC1-RET, KTN1-RET, RET-PTC8, HOOK3-RET, PCM1-RET, TRIM24-RET, RET-PTC6, TRIM27-RET, TRIM33-RET, RET-PTC7, AKAP13-RET, FKBP15-RET, SPECC1L-RET, TBL1XR1-RET, BCR-RET, FGRF1OP-RET, RFG8-RET, RET-PTC9, ACBD5-RET, MYH13-RET, CUX1-RET, KIAA1468-RET, FRMD4A-RET, SQSTM1-RET, AFAP1L2-RET, PPFIBP2-RET, EML4-RET, PARD3-RET, G533C, C609F, C609G, C609R, C609S, C609Y, C611F, C611G, C611S, C611Y, C611W, C618F, C618R, C618S, C620F, C620R, C620S, C630R, C630Y, D631Y, C634F, C634G, C634R, C634S, C634W, C634Y, K666E, E768D, L790F, V804L, V804M, A883F, S891A, R912P, CLIP1-RET, Y806C, RET fusion, RET alteration, RET mutation, RET rearrangement, RET translocation, Neoplasms by Site, Neoplasms, Non-Small Cell Lung Cancer, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Cancer of Lung, Cancer of the Lung, Lung Cancer, Neoplasms, Lung, Neoplasms, Pulmonary, Pulmonary Cancer, Pulmonary Neoplasms, Respiratory Tract Neoplasms, Lung Diseases, Respiratory Tract Diseases, Carcinoma, Bronchogenic, Bronchial Neoplasms, Medullary Thyroid Cancer, Papillary Thyroid Cancer, Thyroid Diseases, Thyroid Neoplasms, Cancer of the Thyroid, Cancer of Thyroid, Neoplasms, Thyroid, Thyroid Ademona, Thyroid Cancer, Thyroid Carcinoma, Endocrine System Diseases, Endocrine Gland Neoplasms, Head and Neck Neoplasms, Thoracic Neoplasms, CNS tumor, Primary CNS tumor, Cancer of Colon, Cancer of the Colon, Colon Cancer, Colon Neoplasms, Colonic Cancer, Neoplasms, Colonic, Malignant tumor of Breast, Mammary Cancer, Mammary Carcinoma, Human, Mammary Neoplasm, Human, Neoplasms, Breast, Tumors, Breast, Human Mammary Carcinoma, Malignant Neoplasm of Breast, Breast Carcinoma, Breast Tumors, Cancer of the Breast, Breast Neoplasms, Breast Cancer, RET Inhibitor, MTC, NSCLC, selpercatinib, neo-adjuvant treatment in early stage NSCLC
Safety and Efficacy Study of IMSA101 in Refractory Malignancies
Open-label, dose escalation (Phase I) and dose expansion (Phase IIA) study of patients
receiving intra-tumoral IMSA101 alone or in combination with an immune checkpoint inhibitor
(ICI) (Phase I and II)
1. Signed informed consent and mental capability to understand the informed consent
2. Male or female patients > 18 years of age
3. Histologically or cytologically documented locally advanced or metastatic solid tumor
malignancies refractory to or otherwise ineligible for treatment with standard-of-care
agents/regimens, including but not limited to:
• Malignant melanoma
• Hormone receptor negative breast cancer
• Gastro-esophageal cancer
• Non-small cell lung cancer
• Head and neck cancer
• Hepatoma
• Renal cell carcinoma
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
5. Evaluable or measurable disease as follows:
• A minimum of 3 RECIST-evaluable lesions: one that is suitable for injection and
biopsied; one non-injected that will be biopsied for abscopal effect; and one
measurable lesion that will be followed for response only.
• Injectable tumors shall be accessed by intralesional (cutaneous) or percutaneous
injection only, including those lesions that are visible, palpable, or detectable
by standard radiographic or ultrasound methods. Neither surgical procedures nor
endoscopically-guided injections including those to endobronchial, endoluminal,
or endosinusial spaces shall be allowed. While no anatomic locations are required
or disallowed, lesions selected for intratumoral injection must, in the opinion
of the investigator:
• Not be immediately adjacent to blood vasculature or other physiologic landmarks
in such a way that will accrue undue safety risk to the patient
• Have longest diameter ≥ 10 mm and ≤ 50 mm
• Be fully efficacy evaluable per RECIST v1.1 criteria
6. Life expectancy > 3 months (Phase I) and > 6 months (Phase IIA)
7. ECG without evidence of clinically meaningful conduction abnormalities or active
ischemia as determined by the investigator
8. Acceptable organ and marrow function as defined below:
• Absolute neutrophil count > 1,500 cells/μL
• Platelets > 50,000 cells/μL
• Total bilirubin ≤ 1.5 times the upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine transaminase (ALT) ≤ 2.5 times ULN. If
liver metastases are present, AST/ALT < 5 times ULN
• Serum creatinine < 1.5 mg/dL and a measured creatinine clearance ≥ 50 mL/min
using the Cockcroft-Gault formula
• Prothrombin time (PT)/partial thromboplastin time (PTT) ≤ 1.5 times ULN
9. Women of child-bearing potential (defined as a female who has experienced menarche and
who has not undergone successful surgical sterilization (hysterectomy, bilateral
salpingectomy, or bilateral oophorectomy) or is not postmenopausal (defined as
amenorrhea for at least 12 consecutive months with an appropriate clinical profile at
the appropriate age, e.g., greater than 45 years) must have a negative serum pregnancy
test prior to first dose of study drug
10. Male and female patients with reproductive potential must agree to use two forms of
highly effective contraception throughout the study
11. Phase I combination only: Demonstrated RECIST stable disease through ≥ 4 consecutive
cycles of an approved PD-1 or PD-L1 targeted ICI with no Grade ≥ 3 CTCAE events
considered by the investigator to be drug-related.
Exclusion Criteria:
1. Anti-cancer therapy within 4 weeks or < 5 half-lives of the first dose of study drug.
2. Failure to recover to Grade 1 or less from clinically significant AEs due to prior
anti-cancer therapy.
3. Known untreated brain metastases or treated brain metastases that have not been stable
(scan showing no worsening of central nervous system (CNS) lesion[s] and no
requirement of corticosteroids) ≥ 4 weeks prior to study enrollment
4. Baseline prolongation of QT/QTc interval (QTc interval > 470)
5. 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 opinion of the
investigator would limit compliance with study requirements
6. Women who are pregnant or breastfeeding
7. Phase I combination only: Prior tumor progression through PD-1 or PD-L1 targeted ICI
therapy.
Trial of Encapsulated Rapamycin (eRapa) for Bladder Cancer Prevention
eRapa (encapsulated rapamycin) will be investigated for secondary prevention in patients with
diagnosed non-muscle invasive bladder cancer (NMIBC) through a phase II double-blind
randomized controlled trial of long-term (one year) prevention with eRapa versus placebo. The
primary hypothesis is that eRapa decreases the risk of cancer relapse for patients with
NMIBC. Secondary hypotheses are that eRapa can improve certain immune parameters and improve
cognition and physical function without adversely affecting patient-reported outcomes and
quality of life.
• Pathologically (histologically) proven diagnosis of non-muscle invasive (Ta, Tis, or
T1) bladder cancer within 90 days prior to enrollment
• Able to give informed consent
• 18 years or older
• Patients must not be taking oral glucocorticoids at the time of registration
• Not have active, uncontrolled infections
• No other prior non-bladder malignancy is allowed except for the following: adequately
treated basal cell 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
survelillance program are also eligible.
• Patients must not be pregnant or nursing, as the use of Intravesical BCG is not
recommended during pregnancy. Women/ men of reproductive potential must have agreed to
use an effective contraceptive method. A woman is considered to be of "reproductive
potential" if she has had menses at any time in the preceding 12 consecutive months.
Examples of effective contraception include hormonal contraception, double barrier
method (condom with spermicidal cream, diaphragms with spermicidal cream, or condoms
with diaphragms), Intrauterine device, and/or partner vasectomy. In addition to
routine contraceptive methods, "effective contraception" also includes heterosexual
celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy
prevention) defined as a hysterectomy, bilateral oophorectomy, or bilateral tubal
ligation. However, if at any point a previously celibate patient chooses to become
heterosexually active during the time period for use of contraceptive measures
outlined in the protocol, he/she is responsible for beginning contraceptive measures.
Both male and female patients will be required to disclose contraception method during
screening and agree to continue to use that contraception method through the end of
their participation in the study.
• Patients must have had all grossly visible papillary tumors removed within 90 days
prior to registration or cystoscopy confirming no grossly visible papillary tumors
within 90 days prior to registration.
• Patients with T1 disease must have cross-sectional imaging of abdomen/pelvis
demonstrating no evidence of nodal involvement or metastatic disease (MRI or CT scan)
within 90 days prior to registration. Patients with T1 disease must have re-resection
confirming ≤ T1 disease within 90 days prior to registration.
• Patients must no have received prior intravesical BCG
Exclusion Criteria:
• Have muscle-invasive or higher (≥T2) bladder cancer
• Unable to give informed consent
• Age 17 or younger
• Taking oral glucocorticoids at the time of registration
• Another cancer requiring active treatment (except basal cell carcinoma or squamous
cell carcinoma of the skin)
• Patients at risk of pregnancy that are unwilling or unable to take effective
contraception during the study period, or patients that are nursing during the study
period. Women/ Men of reproductive potential must have agreed to use an effective
contraceptive method or will be considered ineligible for study participation.
• Evidence of nodal involvement or metastatic disease (MRI or CT scan) within 90 days
prior to registration
• History of prior intravesical BCG
• History of prior Rapamycin treatment
Drug: eRapa, Drug: Placebos
Urinary Bladder, Non-muscle Invasive Bladder Cancer
Testicular Tissue Cryopreservation for Fertility Preservation
Testicular tissue cryopreservation is an experimental procedure where a young boy's
testicular tissue is retrieved and frozen. This technique is reserved for young male patients
who are not yet producing mature sperm, with the ultimate goal that their tissue may be used
in the future to restore fertility when experimental techniques emerge from the research
pipeline.
• Be male at any age.
• Be scheduled to undergo surgery, chemotherapy, drug treatment and/or radiation for the
treatment or prevention of a medical condition or malignancy with risk of causing
permanent and complete loss of subsequent testicular function.
• Or, have a medical condition or malignancy that requires removal of all or part of one
or both testicles.
• Have newly diagnosed or recurrent disease. Those who were not enrolled at the time of
initial diagnosis (i.e., patients with recurrent disease) are eligible if they have
not previously received therapy that is viewed as likely to result in complete and
permanent loss of testicular function.
• Have two testicles if undergoing elective removal of all or part of a testicle for
fertility preservation only. Note: removal of both testicles will limit fertility
preservation options.
• Sign an approved informed consent and authorization permitting the release of personal
health information. The patient and/or the patient's legally authorized guardian must
acknowledge in writing that consent for specimen collection has been obtained, in
accordance with institutional policies approved by the U.S. Department of Health and
• Consent for serum screening tests for infectious diseases [HIV-1, HIV-2, Hepatitis B,
Hepatitis C], to be performed at the time of testicular tissue harvesting.
• Undergo a full history and physical examination and obtain standard pre-operative
clearance (based on the most recent ACC/AHA Guideline for Perioperative Cardiovascular
Evaluation for Noncardiac Surgery) as determined by their primary surgeon.
• Participating in long term follow-up is a requirement of the protocol.
Exclusion Criteria:
• Diagnosed with psychological, psychiatric, or other conditions which prevent giving
fully informed consent.
• Diagnosed with an underlying medical condition that significantly increases their risk
of complications from anesthesia and surgery.
Procedure: Testicular biopsy
Lymphoma, Sarcoma, Cancer, Mycosis Fungoides, Brain and Nervous System, Other, Eye and Orbit, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Male, Carcinoid Tumor, Cardiovascular, Colon, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Nose, Other Digestive Organ, Other Endocrine System, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Leukemia, Other, Hodgkins Lymphoma, Heart, Leukemia, Not Otherwise Specified, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Other Hematopoietic, Small Intestine, Soft Tissue, Unknown Sites, Ill - Defined Sites, Autoimmune Disorders
A Study of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib, Versus Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012)
The goal of this study is to evaluate the efficacy and safety of pembrolizumab plus
belzutifan plus lenvatinib or pembrolizumab/quavonlimab plus lenvatinib versus pembrolizumab
plus lenvatinib as first-line treatment in participants with advanced clear cell renal cell
carcinoma (ccRCC).
The primary hypotheses are (1) pembrolizumab plus belzutifan plus lenvatinib is superior to
pembrolizumab plus lenvatinib with respect to progression-free survival (PFS) and overall
survival (OS), in advanced ccRCC participants and (2) pembrolizumab/quavonlimab plus
lenvatinib is superior to pembrolizumab plus lenvatinib with respect to PFS and OS, in
advanced ccRCC participants.
• Has histologically confirmed diagnosis of RCC with clear cell component
• Has received no prior systemic therapy for advanced ccRCC
• Male participants are abstinent from heterosexual intercourse or agree to use
contraception during and for at least 7 days after last dose of study intervention
with belzutifan and lenvatinib
• Female participants are not pregnant or breastfeeding and are either not a woman of
child-bearing potential (WOCBP) or use a contraceptive method that is highly effective
or are abstinent from heterosexual intercourse during the intervention period and for
at least 120 days after pembrolizumab or pembrolizumab/quavonlimab or for at least 30
days after last dose of lenvatinib or belzutifan, whichever occurs last
• Has adequately controlled blood pressure with or without antihypertensive medications
• Has adequate organ function
• Participants receiving bone resorptive therapy must have therapy initiated at least 2
weeks prior to randomization/allocation
Exclusion Criteria:
• Has a known additional malignancy that is progressing or has required active treatment
within the past 3 years
• Has had major surgery, other than nephrectomy within 4 weeks prior to randomization
• Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has received prior radiotherapy within 2 weeks prior to first dose of study
intervention
• Has hypoxia or requires intermittent supplemental oxygen or requires chronic
supplemental oxygen
• Has clinically significant cardiac disease within 12 months from first dose of study
intervention
• Has a history of interstitial lung disease
• Has symptomatic pleural effusion; a participant who is clinically stable following
treatment of this condition is eligible
• Has preexisting gastrointestinal or non-gastrointestinal fistula
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
or any other form of immunosuppressive therapy within 7 days prior to the first dose
of study treatment
• Has a known psychiatric or substance abuse disorder that would interfere with
requirements of the study
• Has received a live or live-attenuated vaccine within 30 days before the first dose of
study drug; killed vaccines are allowed
• Has an active autoimmune disease that has required systemic treatment in the past 2
years
• Has a history of noninfectious pneumonitis that required steroids or has current
pneumonitis
• Has an active infection requiring systemic therapy
• Has a known history of human immunodeficiency virus (HIV) infection
• Has a known history of Hepatitis B
• Has radiographic evidence of intratumoral cavitation, encasement or invasion of a
major blood vessel
• Has clinically significant history of bleeding within 3 months prior to randomization
• Has had an allogenic tissue/solid organ transplant
Treatment Combination of Durvalumab, Tremelimumab and Enfortumab Vedotin or Durvalumab and Enfortumab Vedotin in Patients With Muscle Invasive Bladder Cancer Ineligible to Cisplatin (VOLGA)
A Global Study to Determine the Efficacy and Safety of Durvalumab in combination with
Tremelimumab and Enfortumab Vedotin or Durvalumab in Combination With Enfortumab Vedotin for
Perioperative Treatment in Patients Ineligible for Cisplatin Undergoing Radical Cystectomy
for Muscle Invasive Bladder Cancer
• Histologically or cytologically documented muscle-invasive TCC of the bladder with
clinical stage T2-T4aN0/1M0 with transitional and mixed transitional cell histology;
• Medically fit for cystectomy and able to receive neoadjuvant therapy;
• Patients who have not received prior systemic chemotherapy or immunotherapy for
treatment of MIBC;
• ECOG performance status of 0,1,2 at enrollment.
• Availability of tumor sample prior to study entry;
• Must have a life expectancy of at least 12 weeks at randomization.
Exclusion criteria:
• Evidence of lymph node (N2+) or metastatic TCC/UC disease at the time of screening.
• Active infection
• Uncontrolled intercurrent illness
• Prior exposure to immune-mediated therapy (with exclusion of Bacillus-Calmette Guerin
[BCG]), including but not limited to other anti-CTLA-4, anti--PD-1, anti PD-L1, or
anti-PD-L2 antibodies.
• Current or prior use of immunosuppressive medication within 14 days before the first
dose of IPs.
The iCat2, GAIN (Genomic Assessment Informs Novel Therapy) Consortium Study
This research study is evaluating the use of specialized testing of solid tumors including
sequencing. The process of performing these specialized tests is called tumor profiling. The
tumor profiling may result in identifying changes in genes of the tumor that indicate that a
particular therapy may have activity. This is called an individualized cancer therapy (iCat)
recommendation. The results of the tumor profiling and, if applicable, the iCat
recommendation will be returned.
• Age -- Age ≤ 30 years at time of initial qualifying solid tumor diagnosis
• Diagnosis -- Histologic diagnosis of solid malignancy (excluding brain tumors and
lymphoma) that meets at least one of the following criteria:
• Refractory, defined as tumor progression after initiation of standard first line
therapy without having achieved a prior partial or complete remission OR Biopsy
proven residual disease at the completion of planned standard initial front-line
therapy.
• Recurrent, defined as tumor progression after achieving a prior partial or
complete remission
• Newly diagnosed high risk disease, defined as having an expected event free
survival of < 50% at 2 years.
• Lacks definitive diagnosis or classical genomic findings after histologic review
and standard molecular testing (rare tumor group).
• Examples include (eligibility not limited to these examples):
• Histology typically associated with a fusion in which fusion is not detected.
• Ewing-like sarcoma
• Undifferentiated sarcoma
• Inflammatory myofibroblastic tumor without ALK fusion
• Infantile fibrosarcoma without NTRK fusion
• Specimen Samples
• Sufficient tumor specimen available to meet the minimum requirements for
profiling from diagnosis or progression / recurrence
--- OR
• Surgery / biopsy planned as part of clinical care that is anticipated to yield
sufficient material to meet the minimum requirements for profiling; OR
• Patient has already had molecular profiling and patient has not yet started
matched targeted therapy based on the report .
Exclusion Criteria:
• No Therapy Planned
-- Patients who have declined further anticancer therapy will be excluded.
• Performance Status
-- Patients with Lansky (age < 16 years) or Karnofsky (age ≥16 years) score < 50 will
be excluded.
• Life Expectancy -- Patients with anticipated life expectancy < 3 months will be
excluded.
Genetic: Genetic testing and GAIN report
Sarcoma, Pediatric Solid Tumor, Brain and Nervous System, Other, Eye and Orbit, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Female, Breast - Male, Carcinoid Tumor, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Heart, Kaposis sarcoma, Small Intestine, Soft Tissue, Ill - Defined Sites
Study of Sparsentan in Patients With Primary Focal Segmental Glomerulosclerosis (FSGS) (DUPLEX)
To determine the long-term nephroprotective potential of treatment with sparsentan as
compared to an angiotensin receptor blocker in patients with primary focal segmental
glomerulosclerosis (FSGS).
1. The patient or parent/legal guardian (as appropriate) is willing and able to provide
signed informed consent, and where required, the patient is willing to provide assent,
prior to any screening procedures.
2. The patient has biopsy-proven primary focal segmental glomerulosclerosis (FSGS) or
documentation of a genetic mutation in a podocyte protein associated with FSGS.
3. Sites within the US: The patient is male or female aged 8 to 75 years, inclusive.
Sites outside the US: The patient is male or female aged 18 to 75 years, inclusive.
4. The patient has a urine protein/creatinine (Up/C) ≥1.5 g/g at screening.
5. The patient has an eGFR ≥30 mL/min/1.73 m2 at screening.
6. Women of childbearing potential (WOCBP) must agree to the simultaneous use of 2
medically accepted methods of contraception from Day 1/Randomization until 90 days
after the last dose of study medication.
7. Males must be surgically sterile (more than 3 months post-vasectomy) or must agree to
the use of medically accepted methods of contraception that are considered highly
reliable from Day 1/Randomization until 90 days after the last dose of study
medication.
Key
Exclusion Criteria:
1. The patient has FSGS secondary to another condition.
2. The patient has positive serological tests of primary or secondary glomerular injury
not consistent with a diagnosis of primary or genetic FSGS.
3. The patient has a history of type 1 diabetes mellitus, uncontrolled type 2 diabetes
mellitus.
4. The patient has undergone any organ transplantation, with the exception of corneal
transplants, or has received certain immunosuppressive medications.
5. The patient has a documented history of heart failure, coronary artery disease or
cerebrovascular disease.
6. The patient has significant liver disease.
7. The patient is positive at screening for the human immunodeficiency virus (HIV) or
markers indicating acute or chronic hepatitis B infection or hepatitis C infection.
8. The patient has a history of malignancy other than adequately treated basal cell or
squamous cell skin cancer or cervical carcinoma within the past 2 years.
9. The patient has disqualifying laboratory abnormalities during a screening.
10. The patient is >18 years of age with a body mass index (BMI) >40, or is ≤18 years of
age with a BMI in the 99th percentile plus 5 units at screening.
11. The patient has a history of alcohol or illicit drug use disorder.
12. The patient has a history of serious side effect or allergic response to any
angiotensin II antagonist or endothelin receptor antagonist.
13. The female patient is pregnant, plans to become pregnant during the course of the
study, or is breastfeeding.
14. The male patient plans to father a child during the course of the study.
15. The patient, in the opinion of the Investigator, is unable to adhere to the
requirements of the study, including the ability to swallow the study medication
capsules whole.
A Research Study to See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease (FLOW)
The researchers are doing this study to see if semaglutide can slow down the growth and
worsening of chronic kidney disease in people with type 2 diabetes. Participants will get
semaglutide (active medicine) or placebo ('dummy medicine'). This is known as participants'
study medicine - which treatment participants get is decided by chance. Semaglutide is a
medicine, doctors can prescribe in some countries for the treatment of type 2 diabetes.
Participants will get the study medicine in a pen. Participants will use the pen to inject
the medicine in a skin fold once a week. The study will close when there is enough
information collected to show clear result of the study. The total time participants will be
in this study is about 3 to 5 years, but it could be longer.
• Male or female, age above or equal to 18 years at the time of signing informed
consent. Japan: Male or female, age above or equal to 20 years at the time of signing
informed consent
• Diagnosed with type 2 diabetes mellitus
• HbA1c less than or equal to 10% (less than or equal to 86 mmol/mol)
• Renal impairment defined either by:
1. serum creatinine-based eGFR greater than or equal to 50 and less than or equal to
75 mL/min/1.73 m^2 (CKD-EPI) and UACR greater than 300 and less than 5000 mg/g or
2. serum creatinine-based eGFR greater than or equal to 25 and less than 50
mL/min/1.73 m^2 (CKD-EPI) and UACR greater than 100 and less than 5000 mg/g
• Treatment with maximum labelled or tolerated dose of a renin-angiotensin-aldosterone
system (RAAS) blocking agent including an angiotensin converting enzyme (ACE)
inhibitor or an angiotensin II receptor blocker (ARB), unless such treatment is
contraindicated or not tolerated. Treatment dose must be stable for at least 4 weeks
prior to the date of the laboratory assessments used for determination of the
inclusion criteria for renal impairment and kept stable until screening
Exclusion Criteria:
• Congenital or hereditary kidney diseases including polycystic kidney disease,
autoimmune kidney diseases including glomerulonephritis or congenital urinary tract
malformations
• Use of any glucagon-like peptide-1 (GLP-1) receptor agonist within 30 days prior to
screening
• Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or
transient ischaemic attack within 60 days prior to the day of screening
• Presently classified as being in New York Heart Association (NYHA) Class IV heart
failure
• Planned coronary, carotid or peripheral artery revascularisation
• Current (or within 90 days) chronic or intermittent haemodialysis or peritoneal
dialysis
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by
a fundus examination performed within the past 90 days prior to screening or in the
period between screening and randomisation. Pharmacological pupil-dilation is a
requirement unless using a digital fundus photography camera specified for non-dilated
examination
Drug: Semaglutide, Drug: Placebo (semaglutide)
Diabetes Mellitus, Type 2, Kidney
UT Southwestern; Parkland Health & Hospital System
Study of Glycerol Phenylbutyrate & Sodium Phenylbutyrate in Phenylbutyrate Naïve Patients With Urea Cycle Disorders
This is a randomized, controlled, open-label parallel arm study to assess the safety,
tolerability, pharmacokinetics and ammonia control, of RAVICTI® as compared to NaPBA in urea
cycle disorder subjects not currently or previously chronically treated with phenylacetic
acid (phenylacetate; PAA) prodrugs. The study design will include: 1) Baseline Period; 2)
Initial Treatment Period; 3) a RAVICTI only Transition Period 4) a RAVICTI only Maintenance
Period; and 5) a RAVICTI only Safety Extension Period. The study will run for approximately
25 weeks.
• Signed informed consent given by the subject or the subject's parent/legal guardian
for those under 18 years of age or the age of consent by local regulation.
• Male and female subjects with a suspected or confirmed UCD diagnosis of any subtype,
except NAGS deficiency.
• Suspected diagnosis is defined as having experienced a HAC or a documented high
ammonia of >=100 µmol/L
• Confirmed diagnosis is determined via enzymatic, biochemical, or genetic testing.
• Requires nitrogen-binding agents according to the judgment of the Investigator
• Birth and older.
• All females of childbearing potential and all sexually active males must agree to
use an acceptable method of contraception from signing the informed consent
throughout the study and for 30 days after the last dose of study drug.
Acceptable forms of contraception are (oral, injected, implanted or transdermal),
tubal ligation, intrauterine device, hysterectomy, vasectomy, or double barrier
methods. Abstinence is an acceptable form of birth control, though appropriate
contraception must be used if the subject becomes sexually active.
Exclusion Criteria:
• Subject has received chronic treatment with an oral phenylbutyrate (RAVICTI, NaPBA,
Pheburane, or other) longer than 14 consecutive days within one year prior to
enrollment.
• Temporary use of NaPBA for acute management of a hyperammonemic crisis in the past is
acceptable.
• Any concomitant illness (e.g., malabsorption or clinically significant liver or
bowel disease) which would preclude the subject's safe participation, as judged
by the Investigator.
• Has undergone liver transplantation, including hepatocellular transplant.
• Subjects on NaBz at Baseline will be excluded if they are viewed by the
Investigator as being unable to undergo NaBz transition to a PAA prodrug during
the Initial Treatment Period.
• Known hypersensitivity to PBA or any excipients of the NaPBA/PBA formulations.
• Pregnant or breast-feeding patients. Women of childbearing potential must have a
pregnancy test performed at the Baseline Visit prior to the start of study drug.
STRATA: Safe Testing of Risk for AsymptomaTic MicrohematuriA
To evaluate the clinical utility associated with the integration of Cxbladder into the
evaluation of subjects presenting with hematuria for evaluation of urothelial carcinoma (UC)
without compromising detection of UC.
• Patient is undergoing investigation of recent confirmed hematuria, as defined by the
AUA/SUFU Guideline (Barocas DA, Boorjian SA, Alvarez RD et al. Microhematuria:
AUA/SUFU guideline, J Urol 2020; 204:778) (by either flexible or rigid
cystoscopy/TURBT), including hematuria subjects referred due to suspicious/positive
imaging, in order to determine the presence of urothelial carcinoma.
• Able to provide a voided urine sample of the required minimum volume
• Able to give written consent
• Able and willing to comply with study requirements
• Aged 18 years or older
Exclusion Criteria
• Prior history of bladder malignancy or pelvic radiotherapy. Prior history prostate or
renal cell carcinoma within the last 5 years.
• Prior genitourinary manipulation (flexible or rigid cystoscopy / catheterisation,
urethral dilation) in the 14 days before urine collection,
• Known current pregnancy
Immunotherapy With Nivolumab and Ipilimumab Followed by Nivolumab or Nivolumab With Cabozantinib for Patients With Advanced Kidney Cancer, The PDIGREE Study
This phase III trial compares the usual treatment (treatment with ipilimumab and nivolumab
followed by nivolumab alone) to treatment with ipilimumab and nivolumab, followed by
nivolumab with cabozantinib in patients with untreated renal cell carcinoma that has spread
to other parts of the body. The addition of cabozantinib to the usual treatment may make it
work better. 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. Cabozantinib may stop the growth of tumor cells by blocking some of
the enzymes needed for cell growth. It is not yet known how well the combination of
cabozantinib and nivolumab after initial treatment with ipilimumab and nivolumab works in
treating patients with renal cell cancer that has spread to other parts of the body.
• STEP I REGISTRATION CRITERIA
• Histologically documented renal cell carcinoma with clear cell component, including
patients who have sarcomatoid or rhabdoid features
• Any metastatic disease, including visceral, lymph node, other soft tissue and bone,
measurable per RECIST 1.1.
• Measurable disease as defined in the protocol.
• Must be intermediate or poor risk patient per International Metastatic Renal Cell
Carcinoma Database (IMDC) criteria (1 or more of the following): Karnofsky performance
status [KPS] < 80, < 1 year from diagnosis [including initial nephrectomy] to systemic
treatment for metastatic disease, hemoglobin less than lower limit of normal [LLN],
corrected calcium concentration greater than upper limit of normal [ULN], absolute
neutrophil count greater than ULN, platelet count > ULN).
• Central nervous system (CNS) disease permitted, if stable and not otherwise causing
symptoms or needing active treatment.
• Karnofsky performance status >= 70%.
• No prior treatment with PD-1, PD-L1, or CTLA-4 targeting agents (including but not
limited to nivolumab, pembrolizumab, pidilizumab, durvalumab, atezolizumab,
tremelimumab, and ipilimumab), or any other drug or antibody specifically targeting
T-cell co-stimulation or checkpoint pathways. The only exception is for prior
treatment with nivolumab or other PD-1/PD-L1/CTLA-4 targeting therapy on pre- or
post-operative trials, as long as > 1 year since completion of systemic therapy.
• No prior previous systemic therapy for renal cell carcinoma (prior HD IL-2 [> 28 days]
and prior adjuvant sunitinib > 180 days since completion and prior immunotherapy as
above are allowed).
• No systemic cancer therapy less than 28 days prior to registration; no radiation
therapy less than 14 days prior to registration. There must be a complete recovery and
no ongoing complications from radiotherapy.
• Not pregnant and not nursing, because this study involves an agent that has known
genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing
potential only, a negative serum or urine pregnancy test done =< 14 days prior to
registration is required.
• Age >= 18 years
• Absolute neutrophil count (ANC) >= 1,500/mm^3.
• Platelet count >= 100,000/mm^3.
• Hemoglobin >= 8 g/dL.
• Calculated (Calc.) creatinine clearance >= 30 mL/min.
• Urine protein =< 1+ or urine protein to creatinine (UPC) ratio < 1.
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (except for patients with known
or likely Gilbert's syndrome, for whom total bilirubin up to 3 mg/dL is allowed with
direct bilirubin =< 20% total bilirubin)
• Aspartate aminotransferase/alanine aminotransferase (AST/ALT) =< 2.5 x upper limit of
normal (ULN) or < 5 x ULN if hepatic metastases present.
• STEP 2 REGISTRATION ELIGIBILITY CRITERIA
• Successful completion of at least 1 cycle of ipilimumab/nivolumab.
• Resolution of any treatment-related adverse events to grade 1 or less per dose
modification section (this criteria does not include any adverse events [AEs] not
attributable to treatment which are present due to disease), with
prednisone-equivalent dosing at 10 mg daily or less. Exceptions for this criteria
include patients receiving replacement hormone treatments (such as levothyroxine for
treatment-related hypothyroidism or glucocorticoid replacement for adrenal
insufficiency). Please contact study chair if further discussion is needed.
• No more than 80 days from last dose of ipilimumab/nivolumab.
Exclusion Criteria:
• Active autoimmune disease requiring ongoing therapy.
• Ongoing acute toxicity > grade 2 from previous treatment.
• History of severe allergic, anaphylactic or other hypersensitivity reactions to
chimeric or humanized antibodies.
• Active hepatitis B/C, or active tuberculosis (PPD response without active TB is
allowed)
• Human immunodeficiency virus (HIV) -infected patients with detectable viral load
within 6 months prior to registration. Patients on effective anti-retroviral therapy
with undetectable viral load within 6 months prior to registration are eligible.
• Concurrent use of immunosuppressive medication including prednisone above 10 mg daily.
• Uncontrolled adrenal insufficiency.
• Uncontrolled hypertension (systolic blood pressure [BP] >150 mmHg or diastolic BP > 90
mmHg).
• Major surgery less than 28 days prior to registration.
• Any serious non-healing wound, ulcer, or bone fracture within 28 days prior to
registration.
• Any arterial thrombotic events within 180 days prior to registration.
• Clinically significant hematuria, hematemesis, or hemoptysis within 12 weeks prior to
registration.
• Cavitating pulmonary lesions or known endotracheal or endobronchial disease
manifestations.
• Lesions encasing or invading any major blood vessels (this does not include tumor
thrombus extending into/through renal vein/inferior vena cava [IVC]). Patients with
tumor thrombus extending into/through renal vein are considered eligible.
• Moderate of severe hepatic impairment (Child-Pugh B or C).
• Any history of untreated pulmonary embolism or deep venous thrombosis (DVT) in the 180
days prior to registration. (Any asymptomatic, treated pulmonary embolism or
asymptomatic, treated deep venous thrombosis > 30 days prior to registration allowed).
• Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms.
• Unstable cardiac arrhythmia within 6 months prior to registration.
• Any gastrointestinal (GI) bleeding =< 180 days, hemoptysis, or other signs of
pulmonary hemorrhage =< 90 days prior to registration.
• History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess,
bowel obstruction, or gastric outlet obstruction within 180 days prior to
registration.
• Active peptic ulcer disease, inflammatory bowel disease, or malabsorption syndrome
within 28 days prior to registration.
• Untreated hypothyroidism (treated hypothyroidism on thyroid replacement therapy is
allowed. Abnormal thyroid-stimulating hormone (TSH) is acceptable with normal T3/free
T4 if treated on thyroid replacement therapy)
• Evidence of pancreatitis, history of organ transplant, or history of congenital QT
syndrome.
• Active treatment with coumarin agents (e.g., warfarin), direct thrombin inhibitors
(e.g., dabigatran), direct Xa inhibitor betrixaban or platelet inhibitors (e.g.,
clopidogrel) within 5 days of registration. Allowed anticoagulants include:
prophylactic use of low-dose aspirin for cardio-protection (per local applicable
guidelines) and low-dose low molecular weight heparins (LMWH), therapeutic doses of
LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban,
apixaban. Allowed also in patients with known brain metastases who are on a stable
dose of the anticoagulant for at least 1 week prior to registration without clinically
significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• Significant cardiac ischemia events (ST elevation myocardial infarction [STEMI] or
non-ST elevation myocardial infarction [NSTEMI]) within 6 months or active NY Heart
Association class 3-4 heart failure symptoms
Clear Cell Renal Cell Carcinoma, Metastatic Malignant Neoplasm in the Bone, Sarcomatoid Renal Cell Carcinoma, Metastatic Malignant Neoplasm in the Soft Tissues, Stage IV Renal Cell Cancer AJCC v8, Metastatic Malignant Neoplasm in the Viscera, Metastatic Malignant Neoplasm in the Lymph Nodes
Pathogenesis of Uric Acid Nephrolithiasis: Role of Pioglitazone/Weight Loss
The investigators will randomize overweight and obese iuan patients to Pio (45 mg/day,
highest approved dose or placebo), WL (10% of body weight, following the established program
used in the Diabetes Prevention Program), or Pio+WL. Participants will be evaluated at
baseline and after 24 weeks of intervention while on a fixed metabolic diet to exclude the
confounding effects of diet and perspiration. The primary endpoint will be change in upH, and
multiple additional endpoints (serum, urine, imaging) will be assessed.
Idiopathic uric acid nephrolithiasis, with last stone analysis showing that stone has >90%
uric acid in composition Age >21 years Any gender, race/ethnicity (from weight loss), but
weight <165 Kg (to fit into MR instrument); eGFR>60ml/min/1.73 m2
Exclusion Criteria:
Bariatric surgery, chronic diarrhea, recurrent UTIs current insulin use use of a
thiazolidinedione in past 2 years contraindication to thiazolidinedione use (liver dz,
pedal edema, CHF NYHA class III/IV, no contraception) Bladder cancer Use of SGLT2-i, GLP-1
analogs, gemfibrozil, topiramate, rifampin Hba1c > 8.5%
A Study To Evaluate The Efficacy And Safety Of Obinutuzumab In Patients With ISN/RPS 2003 Class III Or IV Lupus Nephritis (REGENCY)
This study will evaluate the efficacy, safety, and pharmacokinetics of obinutuzumab compared
with placebo in patients with International Society of Nephrology/Renal Pathology Society
(ISN/RPS) class III or IV lupus nephritis (LN) when added on to standard-of-care therapy
consisting of mycophenolate mofetil (MMF) and corticosteroids.
• Diagnosis of ISN/RPS 2003 Class III or IV LN as evidenced by renal biopsy performed
within 6 months. Participants may co-exhibit Class V disease in addition to either
Class III or Class IV disease
• Urine protein to creatinine ratio greater than or equal to (>/=) 1 on a 24-hour
collection
• Other inclusion criteria may apply
Key
Exclusion Criteria:
• Pregnancy or breastfeeding
• Severe renal impairment or the need for dialysis or renal transplantation
• Receipt of an excluded therapy, including any anti-CD20 therapy less than 9 months
prior to screening or during screening; or cyclophosphamide, tacrolimus, ciclosporin,
or voclosporin during the 2 months prior to screening or during screening
• Significant or uncontrolled medical disease which, in the investigator's opinion,
would preclude patient participation
• Known active infection of any kind or recent major episode of infection
• Intolerance or contraindication to study therapies
• Other exclusion criteria may apply
A Study of TAR-200 in Combination With Cetrelimab, TAR-200 Alone, or Cetrelimab Alone in Participants With Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Intravesical Bacillus Calmette-Guérin Who Are Ineligible for or Elected Not to Undergo Radical Cystectomy (SunRISe-1)
The purpose of this study is to evaluate the overall complete response (CR) rate in
participants treated with TAR-200 in combination with cetrelimab (Cohort 1), or TAR-200 alone
(Cohort 2), or cetrelimab alone (Cohort 3) with Carcinoma in Situ (CIS), with or without
concomitant high-grade Ta or T1 papillary disease.
• Histologically confirmed diagnosis of persistent or recurrent (carcinoma in situ [CIS]
or Tumour in situ [Tis]), with or without papillary disease (T1, high-grade Ta) within
12 months of completion of the last dose of Bacillus Calmette-Guerin (BCG) therapy, in
participants who have received adequate BCG. Mixed histology tumors are allowed if
urothelial differentiation (transitional cell histology) is predominant (example, less
than (<) 20 percent (%) variant histologic subtype). However, the presence of
neuroendocrine, micropapillary, signet ring cell, plasmacytoid, or sarcomatoid
features will make a participant ineligible. For participants with lamina propria
invasion (T1) on the screening biopsy/ transurethral resection of bladder tumor
(TURBT), muscularis propria must be present in order to rule out Muscle Invasive
Bladder Cancer (MIBC)
• All visible papillary disease must be fully resected (absent) prior to randomization
(residual CIS acceptable) and documented in the electronic case report form (eCRF) at
screening cystoscopy
• Participants must be ineligible for or have elected not to undergo radical cystectomy
• BCG-unresponsive high-risk NMIBC after treatment with adequate BCG therapy defined as
a minimum of 5 of 6 full doses of an induction course (adequate induction) plus 2 of 3
doses of a maintenance course, or at least 2 of 6 doses of a second induction course
• Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2
Exclusion Criteria:
• Histologically confirmed, muscle-invasive, locally advanced, nonresectable, or
metastatic urothelial carcinoma (that is, T2, T3, T4, and/or Stage IV
• Must not have had urothelial carcinoma or histological variant at any site outside of
the urinary bladder. Ta/T1/CIS of the upper urinary tract (including renal pelvis and
ureter) is allowable if treated with complete nephroureterectomy more than 24 months
prior to randomization
• Participants with an active, known or suspected autoimmune disease. Participants with
autoimmune disorders not requiring systemic treatment (example, skin conditions such
as vitiligo, psoriasis, alopecia) or conditions requiring hormonal replacement
therapies such as type 1 diabetes mellitus or hypothyroidism are permitted to enroll
• Active hepatitis B or C infection (for example, participants with history of hepatitis
C infection but undetectable hepatitis C virus polymerase chain reaction (PCR) test
and participants with history of hepatitis B infection with positive hepatitis B
surface antigen (HBsAg) antibody and undetectable PCR are allowed)
• Prior therapy with an anti-programmed-cell death 1 (PD-1), anti-PD-ligand 2 (L2)
agent, or with an agent directed to another co-inhibitory T-cell receptor
Non-Contrast Perfusion Using Arterial Spin Labeled MR Imaging for Assessment of Therapy Response in Metastatic Renal Cell Carcinoma
Magnetic Resonance Imaging (MRI) including Arterial Spin Labeling (ASL) will be performed
before, during, and after the treatment, in a total of up to 6 MRI sessions until 7 months
after the first session, or when progression is clinically indicated. Thereafter, patients
will be followed through standard clinical examinations for the next 3 years or until demise,
whichever occurs first.
Clinically, metastatic renal cell carcinoma (RCC) patients are imaged every 2-3 months after
the initiation of anti-angiogenic therapy, since morphological (i.e. size) changes are not
anticipated earlier. However, our preliminary experience has shown functional changes
including perfusion as early as 2-weeks after the initiation of the treatment. T0, T1, and T2
sessions will be performed for this proposal, while T3, T4, and T5 will be performed along
with the clinical imaging sessions. All MR imaging sessions will be scheduled within ±1 or ±2
weeks of the target time period.
The research MR imaging may take approximately an additional 15 minutes per each imaging
session, when done in conjunction with the clinical imaging. The T0, T1, and T2 research MR
imaging sessions will be performed additionally for the purpose of this study, with each
taking approximately one hour.
• Patients with locally advanced or metastatic renal cell carcinoma.
• Patients scheduled to undergo anti-angiogenic treatment or immunotherapy
• Eastern Cooperative Oncology Group (ECOG) Status 0, 1 and 2.
• Women of child-bearing potential must agree to undergo a urine pregnancy screening per
standard Radiology departmental protocol, in place to prevent imaging of pregnant
patients. 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: 1) Has not undergone a hysterectomy or bilateral
oophorectomy; or 2) 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).
• Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
• Subjects may not be receiving any other anti-angiogenic agents, at the time of
enrollment.
• Subjects must not be pregnant since pregnancy is a contraindication to administration
of gadolinium-based contrast agents.
• Any contraindication to MRI per Radiology Department's routine protocol, e.g.
MRI-incompatible objects, including but not limited to medical devices (e.g.
pacemakers, automated implantable cardioverter defibrillators, etc.) and other foreign
bodies.
• Known severe allergic reaction to Gadolinium-based contrast agents.
• Patients with sickle cell disease and patients with other hemolytic anemias (low red
blood count in body).
• Patients with uncontrollable claustrophobia, severe lower back pain, and
uncontrollable tremors, to the point that it would render them unable to tolerate an
MRI study.
Procedure: MRI with ASL
Renal Cell Carcinoma, Kidney
magnetic resonance imaging, arterial spin labeling
Gemcitabine Versus Water Irrigation in Upper Tract Urothelial Carcinoma
There is a high rate of intravesical (bladder) recurrence following extirpative surgery for
upper tract urothelial carcinoma. There is no single established standard of care for
prevention of intravesical recurrence; however, one protocol in common use involves the use
of intravesical gemcitabine instilled into the bladder during surgery and prior to entry into
the bladder. There are barriers to the use of gemcitabine, especially at lower volume
centers. Some evidence suggests that intravesical irrigation with sterile water has
equivalent efficacy to intravesical chemotherapy in prevention of recurrent bladder cancer
following transurethral resection of bladder tumors (TURBT). This study is intended to
compare recurrence rates using intravesical gemcitabine (as a pseudo-standard of care) and
continuous bladder irrigation with sterile water.
• Biopsy proven UTUC with plan for excisional surgery (distal ureterectomy or
nephroureterectomy) with curative intent
• Age 18 •90 years
• Life expectancy > 1 year
• 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.
Female participants who become pregnant or who suspect that they are pregnant should
notify the treating investigator immediately.
• Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
• Concurrent or prior diagnosis of bladder cancer with a disease-free interval of less
than three years.
• Synchronous bilateral upper tract urothelial carcinoma (prior history of contralateral
UTUC is permissible with a disease-free interval of more than three years).
• Plan for radical cystectomy.
• 3.2.4 Suspicion for small bladder capacity (< 100 mL) based on treating urologist's
clinical judgment.
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to gemcitabine or other agents used in study.
Procedure: sterile water irrigation, Drug: Gemcitabine
Urinary Bladder, Urothelial Cancer of Renal Pelvis, Urothelial Carcinoma Ureter
Comparing the Outcome of Immunotherapy-Based Drug Combination Therapy With or Without Surgery to Remove the Kidney in Metastatic Kidney Cancer, the PROBE Trial (PROBE)
This phase III trial compares the effect of adding surgery to a standard of care
immunotherapy-based drug combination versus a standard of care immunotherapy-based drug
combination alone in treating patients with kidney cancer that has spread to other places in
the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab,
ipilimumab, pembrolizumab, and avelumab, may help the body's immune system attack the cancer,
and may interfere with the ability of tumor cells to grow and spread. Axitinib may stop the
growth of tumor cells by blocking some of the enzymes needed for cell growth. Surgery to
remove the kidney, called a nephrectomy, is also considered standard of care; however,
doctors who treat kidney cancer do not agree on its benefits. It is not yet known if the
addition of surgery to an immunotherapy-based drug combination works better than an
immunotherapy-based drug combination alone in treating patients with kidney cancer.
• STEP 1 REGISTRATION: Participants must have a histologically proven diagnosis of clear
cell or non-clear cell renal cell carcinoma. Participants with collecting duct
carcinoma histology are not eligible. Participants with multifocal or bilateral tumors
are eligible
• STEP 1 REGISTRATION: Participants must have primary tumor in place
• STEP 1 REGISTRATION: Participants must have the following scans performed, showing
clinical evidence of measurable or non-measurable metastatic disease:
• Computed tomography (CT) scan of the chest (can be performed without contrast if
CT contrast cannot be given)
• CT of abdomen and pelvis with contrast OR magnetic resonance imaging (MRI) of the
abdomen and pelvis with or without contrast
Scans must be performed within the following timeframes:
• Treatment naive participants must have scans documenting metastatic disease completed
within 90 days prior to study registration
• Previously treated participants must have scans documenting metastatic disease
completed within 90 days prior to first dose of systemic treatment
• STEP 1 REGISTRATION: Participants with symptomatic metastases may have received
palliative radiotherapy or receive palliative radiotherapy after registration
• STEP 1 REGISTRATION: Participants must have no clear contraindications to
nephrectomy
• STEP 1 REGISTRATION: Participants must be offered the opportunity to participate
in specimen bank. With participant consent, specimens must be collected and
submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
• STEP 1 REGISTRATION: Participants must be informed of the investigational nature
of this study and must sign and give informed consent in accordance with
institutional and federal guidelines
• STEP 1 REGISTRATION: As part of the Oncology Patient Enrollment Network (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 REGISTRATION: Participants must have at least one of the following scans
performed 12 weeks (+/- 2 weeks) after starting pre-randomization treatment
• CT scan of the chest (can be performed without contrast if CT contrast cannot be
given)
• CT of abdomen and pelvis with contrast OR MRI of the abdomen and pelvis with or
without contrast Scans must be performed within 28 days prior to randomization.
Response should be assessed by comparing with a CT or MRI of the chest, abdomen and
pelvis obtained prior to starting pre-randomization treatment. Participants with
complete response in all metastatic sites are not eligible to randomize to Step 2
• STEP 2 REGISTRATION: Participants must have one of the following objective statuses
after 12 weeks of pre-randomization treatment
• Stable disease
• Partial response
• The treating investigator believes the patient is deriving clinical benefit from
systemic therapy AND have Zubrod performance status 0-1
• STEP 2 REGISTRATION: Participants must plan to continue the immune-based therapy
received during pre-randomization treatment
• STEP 2 REGISTRATION: Participants must be randomized on or between the 11th and
14th week of protocol-directed pre-randomization treatment therapy
• STEP 2 REGISTRATION: Participants must have received at least one of the minimum
amounts of immunotherapy:
• 2 infusions of nivolumab + 1 infusion of ipilimumab
• 2 infusions of pembrolizumab
• 2 infusions of avelumab
• STEP 2 REGISTRATION: Participants must have a planned surgery date within 42 days
of randomization
• STEP 2 REGISTRATION: Participants must be a surgical candidate as determined by
study urologist. The urology consult should be done within 42 days prior to
randomization
• STEP 2 REGISTRATION: Participants must have a complete physical examination and
medical history within 28 days prior to randomization
• STEP 2 REGISTRATION: Participants must have a Zubrod performance status of 0-1
within 28 days prior to randomization
• STEP 2 REGISTRATION: Total bilirubin =< institutional upper limit of normal (ULN)
(within 28 days prior to randomization)
• STEP 2 REGISTRATION: Aspartate aminotransferase (AST)/alanine aminotransferase
(ALT) =< 3 x institutional upper limit of normal (ULN) (within 28 days prior to
randomization)
• STEP 2 REGISTRATION: Serum creatinine =< 1.5 x the institutional upper limit of
normal (IULN) OR measured OR calculated creatinine clearance >= 50 mL/min using
the Cockcroft-Gault Formula) (must have been drawn and processed within 28 days
prior to randomization)
Exclusion Criteria:
• STEP 1 REGISTRATION: Participants must not have known active brain metastases.
Participants with previously treated brain metastases are eligible if participant has
no neurologic signs or symptoms suggestive of brain metastasis. Brain imaging studies
are not required. If brain imaging studies are performed, they must be negative for
disease
• STEP 1 REGISTRATION: Participants must not have received the following prior treatment
of metastatic renal cell carcinoma:
• Treatment naive participants must not have received any prior lines of systemic
therapy for metastatic renal cell carcinoma beyond the line intended as part of
protocol therapy
• Previously treated participants must not have received any systemic therapy for
metastatic renal cell carcinoma beyond the one regimen received off protocol as
specified in Step 1 pre-randomization treatment
• STEP 1 REGISTRATION: Participants must not have received more than the following
amounts protocol-directed pre-randomization treatment:
• Treatment naive participants must not have received any pre-randomization
treatment.
• Previously treated participants must not be planning to receive any additional
treatment prior to Step 2 randomization, and must not have received more than the
following amounts of pre-randomization treatment:
• 4 infusions of nivolumab
• 4 infusions of ipilimumab
• 4 infusions of pembrolizumab
• 7 infusions of avelumab
• STEP 1 REGISTRATION: Participants must not have received immunotherapy for any cancer
within the following timeframes:
• Treatment naive participants must not have received any immunotherapy within a
year of registration
• Previously treated participants must not have received any other immunotherapy
within a year of the start of off protocol specified pre-randomization treatment
• STEP 1 REGISTRATION: Participants must not have a solitary kidney and not have a
transplanted kidney
• STEP 1 REGISTRATION: No other prior malignancy is allowed except for the following:
adequately treated basal cell or squamous cell skin cancer, any in situ or T1 cancer,
adequately treated stage I or II cancer from which the participant is currently in
complete remission, or any other cancer from which the participant has been disease
free for at least two years
• STEP 1 REGISTRATION: Participants must not have been previously diagnosed with a
medical condition that makes them ineligible for immune based combination therapy or
nephrectomy
• STEP 2 REGISTRATION: Participants must not show progression in the primary tumor.
Participants who are considered to have pseudo progression are allowed
• STEP 2 REGISTRATION: Participants must not have known active brain metastases.
Participants with previously treated brain metastases are eligible if participant has
no neurologic signs or symptoms suggestive of brain metastasis. Brain imaging studies
are not required. If brain imaging studies are performed, they must be negative for
disease
• STEP 2 REGISTRATION: No other prior malignancy is allowed except for the following:
adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer,
adequately treated stage I or II cancer from which the participant is currently in
complete remission, or any other cancer from which the participant has been disease
free for two years
Procedure: Cytoreductive Nephrectomy, Drug: Active Comparator
Metastatic Renal Cell Carcinoma, Metastatic Clear Cell Renal Cell Carcinoma, Stage IV Renal Cell Cancer AJCC v8, Kidney
Comparison of Laser Lithotripsy With and Without Steerable Ureteroscopic Renal Evacuation (SURE)
The purpose of the study is to compare the effects, good and/or bad, of a treatment for
removing kidney stones called the SURE procedure for stone evacuation to the standard
treatment using a basket for stone removal.
• Candidate for ureteroscopy with laser lithotripsy;
• Presence of renal stone(s);
• Be willing and able to return for all study-related follow up procedures; and,
• Have been informed of the nature of the study, agreeing to its requirements, and have
signed the IRB approved informed consent.
Exclusion Criteria:
• BMI > 45;
• Significant comorbidities;
• Bladder, ureteral or kidney abnormalities;
• Pregnant individuals; or
• Unable to meet the treatment and follow up protocol requirements.
Device: SURE, Device: Standard Ureteroscopy (Basketing)
Abatacept in Immune Checkpoint Inhibitor Myocarditis (ATRIUM)
The primary aim is to test whether abatacept, as compared to placebo, is associated with a
reduction in major adverse cardiac events (MACE) among participants hospitalized with
myocarditis secondary to an immune checkpoint inhibitor (ICI). The primary outcome, MACE, is
a composite of first occurrence of cardiovascular death, non-fatal sudden cardiac arrest,
cardiogenic shock, significant ventricular arrythmias, significant bradyarrythmias, or
incident heart failure.
1. Must have provided informed consent in a manner approved by the Investigator's
Institutional Review Board (IRB) prior to any study-related procedure being performed.
If a participant is unable to provide informed consent due to his/her medical
condition, the participant's legally authorized representative may consent on behalf
of the study participant, as permitted by local law and institutional Standard
Operating Procedures;
2. Aged greater than or equal to 18 years at the time of informed consent;
3. Recent use of an FDA-approved immune checkpoint inhibitor (ICI, defined as
administered an immune checkpoint inhibitor ≤ 6 months of myocarditis diagnosis),
alone or in combination with other cancer therapies (i.e. chemotherapy, radiation
therapy or targeted therapy). The FDA-approved ICI could be given as part of a
clinical trial but not in combination with a new investigational agent which may cause
myocarditis;
4. A diagnosis of myocarditis.
5. Hospitalized at the time of randomization;
6. On 1000 mg of solumedrol per day for myocarditis or with an intent to initiate 1000 mg
of solumedrol per day for myocarditis within 24 hours of first administration of study
drug;
7. Serum evidence of ongoing myocardial injury: Serum evidence of ongoing myocardial
injury will be defined as an institutional troponin (either conventional or
high-sensitivity troponin I or T, using the standard institutional assay) with a value
that is ≥5 times the upper limit of the reference standard normal for that
institution. The troponin assay may be adjusted based on sex depending on
institutional standards. This value of troponin of ≥5 times above the institutional
upper limits of normal value must be noted within 10 days prior to potential
randomization. The 10-day period can be in the outpatient or inpatient setting. For
example, a participant with a troponin value that on one occasion was ≥5 times the
upper limits of institutional normal in the 10-day window prior to potential
randomization (whether in the inpatient or outpatient setting), but later decreases
below that threshold, typically due to starting corticosteroids, would still be
considered eligible;
8. The following laboratory parameters, not older than 48 hours at the time of
randomization, and measured as part of usual care:
• Total white blood cell (WBC) count >2,500/μl
• Absolute neutrophil count (ANC) >1,500/μL
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) <20 times the
upper limit of the institutional normal ranges;
9. Women of childbearing potential (i.e., not postmenopausal, or surgically sterilized)
must have a negative highly sensitive urine or serum pregnancy test prior to
randomization. Participating women of childbearing potential must be willing to
consistently use effective methods of contraception from screening until at least 90
days after administration of the last dose of study drug. Participating men must also
be willing to consistently use effective methods of contraception from screening until
at least 90 days after administration of the last dose of study drug; and
10. Must be willing and able to abide by all study requirements and restrictions.
Exclusion Criteria:
1. Must not have experienced any of the following (as defined in the section on the
primary endpoint) in the 30-day period prior to randomization:
• A sudden cardiac arrest
• Cardiogenic shock as defined. A significant bradyarrhythmia (Mobitz type II
second degree atrioventricular block or third degree (complete) atrio-ventricular
(AV) block, for which an intervention with a temporary or permanent pacemaker is
completed or recommended).
• A significant tachyarrhythmia (ventricular fibrillation of any duration or
sustained ventricular tachycardia (>30 seconds, >120 beats per minute); or a
ventricular tachyarrhythmia requiring intervention.
2. Recent (≤2 month) exposure to abatacept or belatacept.
3. Concurrent or recent (≤2 month) use of the following non-corticosteroid
immunosuppressive therapies prior to randomization: mycophenolate, JAK STAT inhibitors
(including but not limited to upadacitinib, tofacitinib, baricitinib, and filgotinib),
tacrolimus, anti-thymocyte globulin, alemtuzumab, infliximab, and plasma exchange. The
use of intravenous immunoglobulin is permitted prior to randomization and during study
treatment.
4. Currently enrolled in another interventional study utilizing systemic agents for the
management of ICI-related toxicities.
5. Female who is pregnant, breastfeeding, or is considering becoming pregnant during the
study or for approximately 90 days after the last dose of study drug.
6. Male who is considering fathering a child or donating sperm during the study or for
approximately 30 days after the last dose of study drug.
7. Any active, chronic, or recurrent viral infection that, based on the investigator's
clinical assessment, makes the participant an unsuitable candidate for the study.
These may include hepatitis B virus (HBV) or hepatitis C virus (HCV), recurrent or
disseminated (even a single episode) herpes zoster, and disseminated (even a single
episode) herpes simplex. Active HBV and HCV are defined as: HBV: hepatitis B surface
antigen (HBs Ag) positive (+) or detected sensitivity on the HBV deoxyribonucleic acid
(DNA) polymerase chain reaction (PCR) qualitative test for Hepatitis B core antibody
(HBc Ab) positive (+) participants; HCV: HCV ribonucleic acid (RNA) detectable in any
participant with anti-HCV antibody (HCV Ab). Patients with active Covid-19 infection
will be excluded. This is defined as the period of ongoing symptoms in the setting of
a positive Covid-19 test, or until 10 days after symptom onset and after resolution of
fever for at least 24 hours, without the use of fever-reducing medications.
8. Known active tuberculosis (TB), history of incompletely treated TB, suspected or known
extrapulmonary TB, suspected or known systemic bacterial or fungal infections;
9. Receipt of any live vaccine within four weeks prior to the first dose of study drug,
or expected need of live vaccination during study participation including at least 90
days after the last dose of IV study drug.
10. Any medical condition that could interfere with, or for which the treatment might
interfere with, the conduct of the study or interpretation of the study results, or
that would, in the opinion of the Investigator, increase the risk of the participant
by participating in the study.
11. Any factors that, in the Investigator's opinion, are likely to interfere with study
procedures, such as history of noncompliance with scheduled appointments.
Drug: Abatacept plus, Drug: Placebo
Cancer, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Thyroid, Urinary Bladder, Small Intestine, Soft Tissue, Unknown Sites, Myocarditis Acute
Tacrolimus/Everolimus vs. Tacrolimus/MMF in Pediatric Heart Transplant Recipients Using the MATE Score (TEAMMATE)
The TEAMMATE Trial will enroll 210 pediatric heart transplant patients from 25 centers at 6
months post-transplant and follow each patient for 2.5 years. Half of the participants will
receive everolimus and low-dose tacrolimus and the other half will receive tacrolimus and
mycophenolate mofetil. The trial will determine which treatment is better at reducing the
cumulative risk of coronary artery vasculopathy, chronic kidney disease and biopsy
proven-acute cellular rejection without an increase in graft loss due to all causes (e.g.
infection, PTLD, antibody mediated rejection).
1. Orthotopic heart transplantation
2. Age < 21 years at time of transplant
3. Stable immunosuppression at the time of randomization with no contraindication to
everolimus, tacrolimus, or mycophenolate mofetil
4. Planned follow-up at a study site for the 30 month duration of the study.
5. Subject or legal adult representative capable of providing informed consent (in
general, assent will be sought for children aged 12 years or older).
Exclusion Criteria:
1. Multi-organ transplant (e.g. heart-lung or heart-liver).
2. Known hypersensitivity to everolimus, sirolimus, tacrolimus or mycophenolate mofetil
(MMF), or to components of the drug products.
3. Patients on maintenance corticosteroid therapy exceeding a dose equivalent of
prednisone 0.1 mg/kg/day at randomization.
4. High-risk for rejection defined as active rejection, recurrent (≥ 2 episodes of grade
2R rejection) cellular rejection, recurrent rejection (≥ 2 episodes of any grade) with
hemodynamic compromise, steroid-resistant rejection or unresolved antibody-mediated
rejection during the first 6 months post-heart transplant
5. Graft dysfunction (LVEF <40% or wedge pressure >22 mmHg or cardiac index <2.2
L/min/m2)
6. Stage 4 or 5 CKD (eGFR <30 ml/min/1.73 m2) or moderate proteinuria (urine protein to
urine creatinine ratio >0.5 mg/mg).
7. Active infection requiring hospitalization or treatment dose medical therapy.
8. Patients with ongoing wound healing problems, clinically significant wound infection
requiring continued therapy or other severe surgical complication in the opinion of
the Site Principal Investigator.
9. Fasting Serum Cholesterol ≥300 mg/dL OR greater than or equal to 7.75 mmol/L, AND
fasting triglycerides ≥2.5x the upper limit of normal (ULN). Note: In case one or both
of these thresholds are exceeded, the patient can only be included after initiation of
appropriate lipid lowering medication, and reduction of serum cholesterol and
triglyceride levels to below exclusion ranges is confirmed.
10. Uncontrolled diabetes mellitus.
11. Diagnosis of post-transplant lymphoproliferative disorder (PTLD) during the first 6
months post-heart transplant.
12. History of non-adherence to medical regimens.
13. Patients who are treated with drugs that are strong inducers or inhibitors of
cytochrome P450 3A4 (CYP3A4) and cannot discontinue the treatment
14. Patients who are pregnant or breast-feeding or intend to get pregnant during the study
period.
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
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
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).
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
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
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
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.
-