Search Results
Pathway to Prevention Study
RATIONALE The accrual of data from the laboratory and from epidemiologic and prevention trials has improved the understanding of the etiology and pathogenesis of type 1 diabetes mellitus (T1DM). Genetic and immunologic factors play a key role in the development of T1DM, and characterization of the early metabolic abnormalities in T1DM is steadily increasing. However, information regarding the natural history of T1DM remains incomplete. The TrialNet Natural History Study of the Development of T1DM (Pathway to Prevention Study) has been designed to clarify this picture, and in so doing, will contribute to the development and implementation of studies aimed at prevention of and early treatment in T1DM. Purpose: TrialNet is an international network dedicated to the study, prevention, and early treatment of type 1 diabetes. TrialNet sites are located throughout the United States, Canada, Finland, United Kingdom, Italy, Germany, Sweden, Australia, and New Zealand. TrialNet is dedicated to testing new approaches to the prevention of and early intervention for type 1 diabetes. The goal of the TrialNet Natural History Study of the Development of Type 1 Diabetes is to enhance our understanding of the demographic, immunologic, and metabolic characteristics of individuals at risk for developing type 1 diabetes. The Natural History Study will screen relatives of people with type 1 diabetes to identify those at risk for developing the disease. Relatives of people with type 1 diabetes have about a 5% percent chance of being positive for the antibodies associated with diabetes. TrialNet will identify adults and children at risk for developing diabetes by testing for the presence of these antibodies in the blood. A positive antibody test is an early indication that damage to insulin-secreting cells may have begun. If this test is positive, additional testing will be offered to determine the likelihood that a person may develop diabetes. Individuals with antibodies will be offered the opportunity for further testing to determine their risk of developing diabetes over the next 5 years and to receive close monitoring for the development of diabetes.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Michelle.Murphy@UTSouthwestern.edu
• Individuals 1 to 45 years old who have an immediate family member with type 1 diabetes (such as a child, parent, or sibling)
• Individuals 1-20 years old who have an extended family member with type 1 diabetes (such as a cousin, niece, nephew, aunt, uncle, grandparent, or half-sibling)
• Have diabetes already
• Have a previous history of being treated with insulin or oral diabetes medications.
• Currently be using systemic immunosuppressive agents (topical and inhaled agents are acceptable)
• Have any known serious diseases
A Study of Pembrolizumab (MK-3475) in Pediatric Participants With an Advanced Solid Tumor or Lymphoma (MK-3475-051/KEYNOTE-051)
This is a two-part study of pembrolizumab (MK-3475) in pediatric participants who have any of the following types of cancer: - advanced melanoma (6 months to <18 years of age), - advanced, relapsed or refractory programmed death-ligand 1 (PD-L1)-positive malignant solid tumor or other lymphoma (6 months to <18 years of age), - relapsed or refractory classical Hodgkin lymphoma (rrcHL) (3 years to <18 years of age), or - advanced relapsed or refractory microsatellite-instability-high (MSI-H) solid tumors (6 months to <18 years of age). Part 1 will find the maximum tolerated dose (MTD)/maximum administered dose (MAD), confirm the dose, and find the recommended Phase 2 dose (RP2D) for pembrolizumab therapy. Part 2 will further evaluate the safety and efficacy at the pediatric RP2D. The primary hypothesis of this study is that intravenous (IV) administration of pembrolizumab to children with either advanced melanoma; a PD-L1 positive advanced, relapsed or refractory solid tumor or other lymphoma; advanced, relapsed or refractory MSI-H solid tumor; or rrcHL, will result in an Objective Response Rate (ORR) greater than 10% for at least one of these types of cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
• Between 6 months and <18 years of age (or between 3 years and <18 years of age for rrcHL participants) on day of signing informed consent/assent (the first 3 participants dosed in Part 1 are to be ≥ 6 years of age)
• Histologically- or cytologically-documented, locally-advanced, or metastatic solid malignancy or lymphoma that is incurable and has failed prior standard therapy, or for which no standard therapy exists, or for which no standard therapy is considered appropriate
• Any number of prior treatment regimens
• Tissue (or lymph node biopsy for rrcHL participants) available from an archival tissue sample or, if appropriate, a newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
• Advanced melanoma or PD-L1-positive advanced, relapsed, or refractory solid tumor or lymphoma
• Measurable disease based on RECIST 1.1 (Or based on IWG [Cheson, 2007] [i.e., measurement must be >15 mm in longest diameter or >10 mm in short axis] for rrcHL participants)
• Participants with neuroblastoma with only metaiodobenzylguanidine (MIBG)-positive evaluable disease may be enrolled
• Lansky Play Scale ≥50 for participants from 6 months up to and including 16 years of age; or Karnofsky score ≥50 for participants >16 years of age
• Adequate organ function
• Female participants of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication
• Female participants of childbearing potential must be willing to use 2 methods of contraception or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication
• Male participants of reproductive potential must agree to use an adequate method of contraception starting with the first dose of study medication through 120 days after the last dose of study medication
• Currently participating and receiving study therapy in, or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the date of allocation/randomization
• Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the date of allocation/randomization
• Prior systemic anti-cancer therapy including investigational agent within 2 weeks prior to study Day 1 or not recovered from adverse events due to a previously administered agent
• Prior radiotherapy within 2 weeks of start of study treatment
• Known additional malignancy that is progressing or requires active treatment with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical carcinoma in situ) with potentially curative therapy, or in situ cervical cancer
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Tumor(s) involving the brain stem
• Severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients
• Active autoimmune disease that has required systemic treatment in past 2 years; replacement therapy (such as thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is acceptable
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Active infection requiring systemic therapy
• Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial through 120 days after the last dose of study medication
• Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand 1 (anti-PD-L1), anti-PD-L2 agent, or any agent directed to another stimulatory or inhibitory T-cell receptor (eg, cytotoxic lymphocyte associated protein-4 [CTLA-4], OX-40, CD137)
• Human immunodeficiency virus (HIV)
• Hepatitis B or C
• Known history of active tuberculosis (TB; Bacillus tuberculosis)
• Received a live vaccine within 30 days of planned start of study medication
• Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Participants who have had an allogeneic hematopoietic transplant >5 years ago are eligible as long as there are no symptoms of Graft Versus Host Disease [GVHD].)
• History or current evidence of any condition, therapy, or laboratory abnormality, or known severe hypersensitivity to any component or analog of the trial treatment, that might confound the results of the trial, or interfere with the participant's participation for the full duration of the study
• Known psychiatric or substance abuse disorders that would interfere with the requirements of the study
Safety Study of Cord Blood Units for Stem Cell Transplants
Background: - Cord blood is blood that is taken from the umbilical cord and placenta of healthy newborns after childbirth. The cord blood collected from a baby is called a cord blood unit. Cord blood units are stored frozen in public cord blood banks. About 10,000 cord blood transplants have been performed in children and adults for blood cancers and other diseases in the world. These transplants have helped save lives and improve treatments. However, not all available units of cord blood have been collected, stored, and licensed according to specific government requirements. These unlicensed units can still be used in transplant, but they can only be given as part of specific research studies. This study will evaluate the safety of giving these unlicensed units by recording any problems that may occur during and after giving the cord blood. Objectives: - To test the safety and effectiveness of unlicensed cord blood units in people who need stem cell transplants. Eligibility: - Individuals who are scheduled to have a stem cell transplant. Design: - Participants will be screened with a medical history and physical exam. - Participants will receive the cord blood unit as part of their stem cell transplant procedure. The transplant will be performed according to the current standard of care for the procedure. - After the transplant, participants will be monitored for up to 1 year. Any problems or side effects from the transplant will be treated as necessary. All outcomes will be reported to the National Cord Blood Program and to the Center for International Blood and Marrow Transplant.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Gevel.Jackson@childrens.com
• INCLUSION CRITERIA:
• Patients of any age or either gender with indications for receipt of investigational HPC-CORD BLOOD who are participating in an NIH-IRB approved clinical trial for unrelated hematopoietic stem cell transplantation.
• Signed informed consent (and assent when applicable). EXCLUSION CRITERIA:
• Patients who are receiving licensed CB products (only)
• Patients who are receiving unlicensed CB products from other CB banks (i.e. NMDP)
Nephrotic Syndrome Study Network (NEPTUNE)
Minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and Membranous nephropathy (MN), generate an enormous individual and societal financial burden, accounting for approximately 12% of prevalent end stage renal disease (ESRD) cases (2005) at an annual cost in the US of more than $3 billion. However, the clinical classification of these diseases is widely believed to be inadequate by the scientific community. Given the poor understanding of MCD/FSGS and MN biology, it is not surprising that the available therapies are imperfect. The therapies lack a clear biological basis, and as many families have experienced, they are often not beneficial, and in fact may be significantly toxic. Given these observations, it is essential that research be conducted that address these serious obstacles to effectively caring for patients. In response to a request for applications by the National Institutes of Health, Office of Rare Diseases (NIH, ORD) for the creation of Rare Disease Clinical Research Consortia, a number of affiliated universities joined together with The NephCure Foundation the NIDDK, the ORDR, and the University of Michigan in collaboration towards the establishment of a Nephrotic Syndrome (NS) Rare Diseases Clinical Research Consortium. Through this consortium the investigators hope to understand the fundamental biology of these rare diseases and aim to bank long-term observational data and corresponding biological specimens for researchers to access and further enrich.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Bethany.Roehm@UTSouthwestern.edu
• Documented urinary protein excretion ≥1500 mg/24 hours or spot protein: creatinine ratio equivalent at the time of diagnosis or within 3 months of the screening/eligibility visit.
• Scheduled renal biopsy Cohort B (non-biopsy, cNEPTUNE)
• Age <19 years of age
• Initial presentation with <30 days immunosuppression therapy
• Proteinuria/nephrotic
• UA>2+ and edema OR
• UA>2+ and serum albumin <3 OR
• UPC > 2g/g and serum albumin <3 Exclusion Criteria (Cohort A&B):
• Prior solid organ transplant
• A clinical diagnosis of glomerulopathy without diagnostic renal biopsy
• Clinical, serological or histological evidence of systemic lupus erythematosus (SLE) as defined by the ARA criteria. Patients with membranous in combination with SLE will be excluded because this entity is well defined within the International Society of Nephrology/Renal Pathology Society categories of lupus nephritis, and frequently overlaps with other classification categories of SLE nephritis (68)
• Clinical or histological evidence of other renal diseases (Alport, Nail Patella, Diabetic Nephropathy, IgA-nephritis, monoclonal gammopathy (multiple myelomas), genito-urinary malformations with vesico-urethral reflux or renal dysplasia)
• Known systemic disease diagnosis at time of enrollment with a life expectancy less than 6 months
• Unwillingness or inability to give a comprehensive informed consent
• Unwillingness to comply with study procedures and visit schedule
• Institutionalized individuals (e.g., prisoners)
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.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
• 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.
• 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
Does Caudal Block Increase the Incidence of Urethrocutaneous Fistula Formation Following Hypospadias Repair in Infants?
This is a prospective randomized multi-center non-inferiority trial conducted through the Pediatric Regional Anesthesia Network study sites to determine if caudal block increases the incidence of urethrocutaneous fistula following distal or mid shaft hypospadias repair compared with penile nerve block.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Kiley.Poppino@UTSouthwestern.edu
• infants/ children with midshaft or distal hypospadias undergoing primary single stage repair in one of the Pediatric Regional Anesthesia Network participating centers.
• prior hypospadias surgery,
• proximal or penoscrotal hypospadias,
• abnormal caudal anatomy or spinal dysraphism,
• cyanotic congenital heart disease,
• infection or rash at the block injection site.
Multicenter Trial of Congenital Pulmonic Valve Dysfunction Studying the SAPIEN 3 THV With the Alterra Adaptive Prestent (ALTERRA)
To demonstrate the safety and functionality of the Edwards Alterra Adaptive Prestent in conjunction with the Edwards SAPIEN 3 Transcatheter Heart Valve (THV) System in patients with a dysfunctional right ventricular outflow tract/pulmonary valve (RVOT/PV) who are indicated for treatment of pulmonary regurgitation (PR).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Kirstie.LeDoux@UTSouthwestern.edu
• The patient/patient's legally authorized representative has been informed of the nature of the study, agrees to its provisions and has provided written informed consent.
• Pediatric or adult patent whose weight is ≥ 20 kg (44 lbs).
• The patient has a dysfunctional RVOT/PV.
• RVOT/PV proximal and distal landing zone diameter ≥ 27 mm and ≤ 38 mm and/or minimum of 35 mm from contractile tissue to lowest pulmonary artery takeoff immediately prior to Alterra Prestent insertion.
• Active infection requiring current antibiotic therapy (if temporary illness, patient may be a candidate 2 weeks after discontinuation of antibiotics).
• History of or active endocarditis (active treatment with antibiotics) within the past 180 days.
• Leukopenia (WBC < 2000 cells/μL), anemia (Hgb < 7 g/dL), thrombocytopenia (platelets < 50,000 cells/μL) or any known blood clotting disorder.
• Inappropriate anatomy for introduction and delivery of the Alterra Adaptive Prestent or the SAPIEN 3 THV.
Study of Biomarker-Based Treatment of Acute Myeloid Leukemia
This screening and multi-sub-study Phase 1b/2 trial will establish a method for genomic screening followed by assigning and accruing simultaneously to a multi-study "Master Protocol (BAML-16-001-M1)." The specific subtype of acute myeloid leukemia will determine which sub-study, within this protocol, a participant will be assigned to evaluate investigational therapies or combinations with the ultimate goal of advancing new targeted therapies for approval. The study also includes a marker negative sub-study which will include all screened patients not eligible for any of the biomarker-driven sub-studies.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
• Adults, age 60 years or older at the time of diagnosis
• Subjects or their legal representative must be able to understand and provide written informed consent
• Cohort Inclusion Criteria - Group A: Subjects must have previously untreated acute myeloid leukemia (AML) according to the WHO classification with no prior treatment other than hydroxyurea. Prior therapy for myelodysplastic syndrome (MDS), myeloproliferative syndromes (MPD), or aplastic anemia is permitted but not with hypomethylating agents.
• Cohort Inclusion Criteria - Group B: Subjects must have relapsed or refractory AML according to the WHO classification. For study purposes, refractory AML is defined as failure to ever achieve CR or recurrence of AML within 6 months of achieving CR; relapsed AML is defined as all others with disease after prior remission. (Group B is not currently recruiting. Expected to begin recruiting in 3rd quarter 2017.)
• Isolated myeloid sarcoma (meaning, patients must have blood or marrow involvement with AML to enter the study)
• Acute promyelocytic leukemia
• Symptomatic central nervous system (CNS) involvement by AML
• Signs of leukostasis requiring urgent therapy
• Disseminated intravascular coagulopathy with active bleeding or signs of thrombosis
• Patients with psychological, familial, social, or geographic factors that otherwise preclude them from giving informed consent, following the protocol, or potentially hamper compliance with study treatment and follow-up
• Any other significant medical condition, including psychiatric illness or laboratory abnormality, that would preclude the patient participating in the trial or would confound the interpretation of the results of the trial
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).
Call 214-648-5005
studyfinder@utsouthwestern.edu, kara.lorduy@childrens.com
• Orthotopic heart transplantation
• Age < 21 years at time of transplant
• Stable immunosuppression at the time of randomization with no contraindication to everolimus, tacrolimus, or mycophenolate mofetil
• Planned follow-up at a study site for the 30 month duration of the study.
• Subject or legal adult representative capable of providing informed consent (in general, assent will be sought for children aged 12 years or older).
• Multi-organ transplant (e.g. heart-lung or heart-liver).
• Known hypersensitivity to everolimus, sirolimus, tacrolimus or mycophenolate mofetil (MMF), or to components of the drug products.
• Patients on maintenance corticosteroid therapy exceeding a dose equivalent of prednisone 0.1 mg/kg/day at randomization.
• 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
• Graft dysfunction (LVEF <40% or wedge pressure >22 mmHg or cardiac index <2.2 L/min/m2)
• 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).
• Active infection requiring hospitalization or treatment dose medical therapy.
• 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.
• 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.
• Uncontrolled diabetes mellitus.
• Diagnosis of post-transplant lymphoproliferative disorder (PTLD) during the first 6 months post-heart transplant.
• History of non-adherence to medical regimens.
• Patients who are treated with drugs that are strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) and cannot discontinue the treatment
• Patients who are pregnant or breast-feeding or intend to get pregnant during the study period.
A Study of Therapeutic Iobenguane (131-I) and Vorinostat for Recurrent or Progressive High-Risk Neuroblastoma Subjects (OPTIMUM)
The purpose of this study is to evaluate the efficacy and safety of 131I-MIBG in combination with Vorinostat in patients with Recurrent or Progressive neuroblastoma
Call 833-722-6237
canceranswerline@utsouthwestern.edu
• Subjects with a diagnosis of iobenguane avid, high-risk neuroblastoma based on Revised INRC criteria at the time of study enrollment with recurrent or progressive disease at any time prior to enrollment, regardless of overall response to frontline therapy, where frontline therapy includes a minimum of 4 cycles of induction therapy at any time prior to enrollment.
• May have had prior 131I-MIBG therapy, provided:
• It has been at least 6 months from the date of last 131I-MIBG ;
• Response was other than progressive disease on first restaging after 131I-MIBG ;
• Prior 131I-MIBG was given as monotherapy and not in combination with systemic anticancer agents;
• Cumulative lifetime dose of 131I-MIBG at enrollment does not exceed 18 mCi/kg.
• All soft tissue lesions identified on CT/MRI scans must be iobenguane avid lesions on an (123I)-iobenguane scan, or
• any progressive non-iobenguane avid lesion is proven by biopsy to be a non-neuroblastoma lesion.
• any other non-avid lesion is comprised of a fibrotic or scarred mass as shown by routine imaging and confirmed by the investigator.
• Adequate cryopreserved autologous peripheral blood stem cells or bone marrow (at least 2 aliquots of 2.0 × 10exp6 CD34/kg at the time of study enrollment).
• If a male, must agree to use an adequate contraception method as deemed appropriate by the Investigator (e.g., vasectomy, condoms) or partner using effective contraception and to not donate sperm during the study and for 90 days after receiving the last dose of study drug.
• If a female of childbearing potential, have a negative serum pregnancy test result prior to each dosing and, if sexually active, be practicing an effective method of birth control [e.g., intrauterine device, double-barrier method (i.e., diaphragm, or a cervical cap) with intravaginal spermicidal foam, cream or gel], or male partner sterilization throughout the study.
• Age at study entry ≥1 year.
• Previous platelet transfusions are permitted, as long as the subject has a platelet count ≥50,000/μL without transfusion support for at least 1 week.
• Subjects must have a minimum pulse oximetry measurement of at least 94% at baseline.
• An absolute neutrophil count ≥750/μL without growth factor for 5 days.
• Liver function parameter results: total bilirubin ≤2 × upper limit of normal for age, and Serum alanine aminotransferase (glutamic-pyruvic transaminase) and serum aspartate aminotransferase (glutamic-oxaloacetic transaminase) ≤ 10 times the upper limit of normal (for all sites, the upper limit of normal for alanine aminotransferase is defined as 45 U/L).
• Normal thyroid function as measured by T4 or TSH or have abnormal results that are not considered clinically important by the Investigator or may be receiving levothyroxine.
• Cardiac Function: shortening fraction of ≥ 27% by echocardiogram or ejection fraction ≥ 50% documented by echocardiogram or radionuclide angiogram within 1 month prior to Visit 1 (Baseline).
• Karnofsky Performance Status (for subjects >16 years of age) or the Lansky Performance Status Performance Status (for subjects 1 to 16 years of age) ≥50%.
• Full recovery from the toxic effects of any prior therapy.
• Coagulation Function:
• International Normalized Ratio (INR) < 1.5
• Partial thromboplastin time (PTT) < 1.5 times upper limit of normal.
• Subjects within 5 half-lives after any antibody-based immunotherapy, or have not recovered from effects of any biologic therapy.
• Subjects <12 weeks after myeloablative therapy with autologous stem cell transplant.
• Subjects who have had an allogeneic stem cell treatment less than 4 months from Visit 1 are excluded. Those who have received allogeneic stem cell treatment more than 4 months from Visit 1 must have recovered and have no active graft versus host disease (GVHD) to be eligible.
• Subjects must not have received radiation for a minimum of 2 weeks prior to study enrollment. Subjects whose only site(s) of disease have been radiated are eligible as long as the subject has MIBG avidity 2 weeks after completion of radiation. A minimum of 12 weeks prior to study enrollment is required following prior large field radiation therapy (ie, craniospinal, whole abdominal, total lung, > 50% marrow space)
• History of total body irradiation.
• Subjects do not have adequate renal function defined as GFR ≥ 70 mL/min/1.73 m2 either by creatinine clearance or radioisotope direct measurement or by calculation with the Schwartz formula
• Subjects who are on hemodialysis.
• Pregnancy or breastfeeding.
• Significant active infections including active hepatitis B, or hepatitis C infection, or known infection with human immunodeficiency virus (HIV) (testing for HIV is not required prior to study entry).
• Clinically important cardiac, pulmonary, and hepatic impairment.
• Vorinostat treatment exclusion criteria (subjects, who meet any one of these criteria and otherwise meet eligibility criteria, are still eligible for 131I-MIBG monotherapy)
• Since valproic acid has HDAC inhibitory activity, patients must not have received valproic acid within 30 days of study entry.
• Since vorinostat may prolong the QT interval, patients must not be receiving other medications known to prolong the QT interval at the time of study entry . Pentamidine must not have been received within 1 week of study enrollment.
• Patients with a history of deep venous thrombosis that was not associated with the presence of a central venous catheter.
• Patients who are receiving Coumadin.
Accelerated v's Standard BEP Chemotherapy for Patients With Intermediate and Poor-risk Metastatic Germ Cell Tumours (P3BEP)
The purpose of this study is to determine whether accelerated BEP chemotherapy is more effective than standard BEP chemotherapy in males with intermediate and poor-risk metastatic germ cell tumours.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
• Age ≥ 11 years and ≤ 45 years on the date of randomisation
• Histologically or cytologically confirmed germ cell tumour (non-seminoma or seminoma); or Exceptionally raised tumour markers (AFP ≥ 1000ng/mL and/or HCG ≥ 5000 IU/L) without histologic or cytologic confirmation in the rare case where pattern of metastases consistent with GCT, high tumour burden, and a need to start therapy urgently
• Primary arising in testis, ovary, retro-peritoneum, or mediastinum
• Metastatic disease or non-testicular primary
• Intermediate or poor prognosis as defined by IGCCC classification3 (modified with different LDH criteria for intermediate risk non-seminoma, and inclusion of ovarian primaries). (See protocol for more information).
• Adequate bone marrow function with ANC ≥1.0 x 10^9/L, Platelet count ≥100 x 10^9/L
• Adequate liver function where bilirubin must be ≤1.5 x ULN, except participants with Gilbert's Syndrome where bilirubin must be ≤2.0 x ULN; ALT and AST must be ≤2.5 x ULN, except if the elevations are due to hepatic metastases, in which case ALT and AST must be ≤ 5 x ULN
• Adequate renal function with estimated creatinine clearance of ≥60 ml/min according to the Cockcroft-Gault formula, unless calculated to be < 60 ml/min or borderline in which case GFR should be formally measured, eg. with EDTA scan
• ECOG Performance Status of 0, 1, 2, or 3
• Study treatment both planned and able to start within 14 days of randomisation.
• Willing and able to comply with all study requirements, including treatment, timing and nature of required assessments
• Able to provide signed, written informed consent
• Other primary malignancy (EXCEPT adequately treated non-melanomatous carcinoma of the skin, germ cell tumour, or other malignancy treated at least 5 years previously with no evidence of recurrence)
• Previous chemotherapy or radiotherapy, except if patient has pure seminoma relapsing after adjuvant radiotherapy or adjuvant chemotherapy with 1-2 doses of single agent carboplatin or if patient has non-seminoma and poor prognosis by IGCCC criteria in the rare case where low-dose induction chemotherapy is given prior to registration because patient is not fit enough to receive protocol chemotherapy (eg. organ failure, vena cava obstruction, overwhelming burden of disease). In these instances acceptable regimens include cisplatin 20 mg/m^2 days 1-2 and etoposide 100 mg/m^2 days 1-2; carboplatin AUC 3 days 1-2 and etoposide 100 mg/m^2 days 1-2; or baby-BOP. Patients must meet all other inclusion and exclusion criteria at the time of registration. Additionally participants who need to start therapy urgently prior to completing study-specific baseline investigations may commence study chemotherapy prior to registration and randomisation. Such patients must be discussed with the coordinating centre prior to registration, and must be registered within 10 days of commencing study chemotherapy.
• Significant cardiac disease resulting in inability to tolerate IV fluid hydration for cisplatin
• Significant co-morbid respiratory disease that contraindicates the use of bleomycin
• Peripheral neuropathy ≥ grade 2 or clinically significant sensorineural hearing loss or tinnitus
• Concurrent illness, including severe infection that may jeopardize the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety
• Inadequate contraception. Men must use 2 effective methods of contraception, including use of a condom, during chemotherapy and for a year after completing chemotherapy.
• Known allergy or hypersensitivity to any of the study drugs
• Presence of any psychological, familial, sociological or geographical condition that in the opinion of the investigator would hamper compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse The above inclusion and exclusion criteria will apply to stage 1 (n=150) and stage 2 (n=500 including stage 1) of the study. All sites will participate in both stages of the study with the exception of the Children's Oncology Group who will be participate in stage 1 only.
GammaPod Registry and Quality of Life Nomogram (GCC 1876)
This study is a prospective, single arm study (registry) summarizing patient-level adverse-event and tumor outcomes as well as a number of feasibility and dosimetric characteristics of delivering a single-fraction boost with the GammaPod.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
• The patient must sign consent for study participation.
• The patient must be female and have a diagnosis of an invasive or non-invasive breast cancer that was treated surgically by a partial mastectomy.
• The patient must be deemed an appropriate candidate for breast conserving therapy (i.e. not pregnant, never had radiation to the treated breast, breast size would allow adequate cosmesis after volume loss from partial mastectomy).
• Patients with involved lymph nodes are candidates for the study.
• Surgical margins are negative for invasive (no tumor on ink) or non-invasive breast cancer (2 mm negative margin).
• The greatest dimension of the tumor is less than 4cm before surgery.
• Multifocal disease is allowed if it was removed by a single lumpectomy resection and the patient remained a candidate for breast conservation.
• Age 18 years and older.
• Women of childbearing potential (pre-menopausal defined as having a menstrual period within the past 1 year) must have a negative serum pregnancy test or complete a pregnancy waiver form per institutional policy.
• The surgical cavity is clearly visible on CT images. Of note, clips are not required but recommended.
• The patient must weigh less than 150Kg (330lb), which is the limit of the imaging couch.
• The patient must be less than 6'6" in height.
• The patient must feel comfortable in the prone position.
• Diagnosis of prior contralateral breast cancer is allowed.
• Diagnosis of synchronous bilateral cancers is allowed. In this case if bilateral boosts are required, a patient would not have both treatments on the same day.
• Oncoplastic reduction surgery is allowed if the lumpectomy cavity can be clearly visualized.
• Patients with proven multi-centric carcinoma (tumors in different quadrants of the breast or tumor separated by at least 4 cm).
• Prior radiation therapy to that breast or that hemi thorax.
• Unable to fit into the immobilization breast cup with an adequate seal.
• Male gender.
• Patient cannot comfortably be set up in the prone position (i.e. physical disability)
• Unable to fit into the breast immobilization device due to breast size or other anatomical reason.
• Mastectomy is the surgery performed.
• Patient has received prior radiotherapy to the involved breast.
• Tumor bed is less than 3 mm from the skin surface.
• Greater than 50% of the target volume is above the upper border of the table.
• Patients with skin involvement, regardless of tumor size.
• Patients with connective tissue disorders specifically systemic lupus erythematosis, scleroderma, or dermatomyositis.
• Patients with psychiatric or addictive disorders that would preclude obtaining informed consent.
• Patients who are pregnant or lactating due to potential exposure of the fetus to RT and unknown effects of RT to lactating females.
• Patients with breast implants/tissue expanders or flap reconstruction.
Mechanisms of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction
The global objective of this study is to determine the mechanisms of exercise intolerance and dyspnea on exertion (DOE) in patients with HFpEF and based on this pathophysiology, test whether specific exercise training programs (whole body vs single leg) will result in improved exercise tolerance.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Mary.Childers@UTSouthwestern.edu
• signs and symptoms of heart failure
• an ejection fraction > 0.50
• objective evidence of diastolic dysfunction
• age < 60 years
• BMI > 50 kg/m2
• PDE5 inhibitor use
• Severe valvular disease
• Severe COPD
• CKD 4 or higher
• Contra-indication to MRI.