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.
A Study of ASP2138 in Adults With Stomach Cancer or Pancreatic Cancer
ASP2138 is a potential new treatment for people with stomach cancer, gastroesophageal
junction cancer, or pancreatic cancer. Before ASP2138 is available as a treatment, the
researchers need to understand how it is processed by and acts upon the body. They do this to
find a suitable dose and to check for potential medical problems from the treatment.
People who are 18 years or older can take part. This is an open-label study. This means that
people in this study will know that they will receive ASP2138.
The study will have 2 phases. Phase 1 is called dose escalation. Different small groups of
people will take lower to higher doses of ASP2138. Medical problems will be recorded at each
dose. This is done to find suitable doses of ASP2138 to use later in the study. Doctors will
also check how each type of cancer is responding to ASP2138.
Phase 1b is called dose expansion. Other different small groups will take part, and will take
suitable doses of ASP2138 found from phase 1. This phase will check how each type of cancer
responds to ASP2138. The response to ASP2138 is measured using x-rays, scans and blood tests.
Doctors will continue to check all medical problems throughout the study.
ASP2138 will be given through a vein in the arm. This is called an infusion. People will
continue to receive treatment until: their disease gets worse; they have medical problems
they can't tolerate; they ask to stop treatment; the doctors decide that continuing treatment
is no longer in that person's best interest; the study is ended by the sponsor. Study doctors
will check for any medical problems from ASP2138. Other checks will include physical exams,
checking the nervous system, laboratory tests and vital signs. Nervous system checks include
checking reflexes, balance, movement and muscle strength. Vital signs include body
temperature, blood pressure and pulse. Electrocardiograms (ECG) will be done to check the
heart rhythm during the study. People will receive ASP2138 in a hospital. They will give
blood samples and study doctors will check for medical problems. People will also visit the
clinic on certain days during their treatment, with extra visits during the first 3 cycles of
treatment.
People will visit the clinic after treatment has finished. The study doctors will check for
more medical problems. Other checks will include physical exams, laboratory tests and vital
signs. People will also have an ECG.
After this, people will visit the clinic for a check-up several times. The number of visits
and checks done at each visit will depend on the health of each person and whether they
completed their treatment or not.
• Participant is considered an adult according to local regulation at the time of
signing the informed consent form (ICF).
• Female participant is not pregnant, confirmed by serum pregnancy test and medical
evaluation by interview and at least 1 of the following conditions apply:
• Not a woman of childbearing potential (WOCBP)
• WOCBP who agrees to follow the contraceptive guidance from the time of informed
consent through at least 6 months after final study intervention administration.
• Female participant must agree not to breastfeed starting at screening and throughout
the study period and for 6 months after the final study intervention administration.
• Female participant must not donate ova starting at screening and throughout the study
period and for 6 months after the final study intervention administration.
• Male participant with female partner(s) of childbearing potential (including
breastfeeding partner) must agree to use contraception throughout the treatment period
and for 6 months after the final study intervention administration.
• Male participant must not donate sperm during the treatment period and for 6 months
after the final study intervention administration.
• Male participant with pregnant or breastfeeding partner(s) must agree to remain
abstinent or use a condom for the duration of the pregnancy or time partner is
breastfeeding throughout the study period and for 6 months after the final study
intervention administration.
• Participant's tumor sample is positive for claudin (CLDN)18.2 expression by central
immunohistochemistry (IHC) testing.
• Participant has radiographically-confirmed, locally advanced, unresectable or
metastatic disease within 28 days prior to the first dose of study intervention.
• Participant has measurable disease according to Response Evaluation Criteria in Solid
Tumors (RECIST) 1.1 within 28 days prior to the first dose of study intervention. For
participant with only 1 measurable lesion and prior radiotherapy, the lesion must be
outside the field of prior radiotherapy or must have documented progression following
radiation therapy.
• Participant has QT interval by Fredericia (QTcF) =< 470 msec.
• Participant agrees not to participate in another interventional study while receiving
study treatment in the present study.
• Participant has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
1.
• Participant has predicted life expectancy >= 12 weeks.
• Participant must meet all of criteria based on laboratory tests within 7 days prior to
the first dose of study drug. In case of multiple laboratory data within this period,
the most recent data should be used. If a participant has received a recent blood
transfusion, the laboratory tests must be obtained >= 2 weeks after any blood
transfusion.
Disease Specific Criteria: Gastric/GEJ Cancer
• Participant has histologically confirmed gastric or gastroesophageal junction (GEJ)
adenocarcinoma.
• Participant with gastric or GEJ adenocarcinoma who has progressed, is intolerant, has
refused, or for whom there is no standard approved therapies that impart significant
clinical benefit (no limit to the number of prior treatment regimens).
Disease Specific Criteria: Pancreatic Cancer
• Participant has histologically or cytologically confirmed pancreatic adenocarcinoma.
• Participant with pancreatic adenocarcinoma who has progressed, is intolerant, has
refused, or for whom there is no standard approved therapies that impart significant
clinical (no limit to the number of prior treatment regimens).
Exclusion Criteria:
• Participant has received other investigational agents, or antineoplastic therapy
including immunotherapy or devices concurrently or within 21 days or 5 times the
half-life, whichever is shorter, prior to first dose of study intervention
administration.
• Participant has any condition which makes the participant unsuitable for study
participation.
• Participant has known immediate or delayed hypersensitivity or contraindication to any
component of study treatment.
• Participant has had prior severe allergic reaction or intolerance to known ingredients
of ASP2138 or other antibodies, including humanized or chimeric antibodies.
• Participant weighs < 40 kg.
• Participant has received systemic immunosuppressive therapy, including systemic
corticosteroids 14 days prior to first dose of study intervention. Participant using a
physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30
mg per day of hydrocortisone or up to 10 mg per day of prednisone), receiving a single
daily dose of systemic corticosteroids or receiving systemic corticosteroids as
pre-medication for radiologic imaging contrast use are allowed.
• Participant has a complete gastric outlet syndrome or a partial gastric outlet
syndrome with persistent/recurrent vomiting.
• Participant has significant gastric bleeding and/or untreated gastric ulcers that
exclude the participant from participation.
• Participant has symptomatic CNS metastases or participant has evidence of unstable CNS
metastases even if asymptomatic (e.g., progression on scans). Participants with
previously treated CNS metastases are eligible, if they are clinically stable and have
no evidence of CNS progression by imaging for at least 4 weeks prior to start of study
treatment and are not requiring immunosuppressive doses of systemic steroids (> 30 mg
per day of hydrocortisone or > 10 mg per day of prednisone or equivalent) for longer
than 2 weeks.
• Participant is known to have HIV infection. However, participants with cluster of
differentiation (CD4) + T cell counts >= 350 cells/µL and no history of acquired
immunodeficiency syndrome (AIDS)-defining opportunistic infections within the past 6
months are eligible. NOTE: Screening for human immunodeficiency virus (HIV) infection
should be conducted per local requirements.
• Participant is known to have active hepatitis B (positive hepatitis B surface antigen
[HBsAg]) or hepatitis C infection. Testing is required for known history of these
infections or as mandated by local requirements. NOTE: Screening for these infections
should be conducted per local requirements.
• For participant who is negative for HBsAg, but hepatitis B core antibody (HBc Ab)
positive, a hepatitis B virus (HBV) deoxyribonucleic acid (DNA) test will be
performed and if positive the participant will be excluded.
• Participant with positive hepatitis C virus (HCV) serology, but negative HCV
ribonucleic acid (RNA) test results are eligible.
• Participant treated for HCV with undetectable viral load results are eligible
• Participant has had within 6 months prior to first dose of study intervention any of
the following: unstable angina, myocardial infarction, ventricular arrhythmia
requiring intervention or hospitalization for heart failure.
• Participant has active infection requiring systemic therapy that has not completely
resolved within 7 days prior to the start of study intervention.
• Participant has active autoimmune disease that has required systemic immunosuppressive
treatment within the past 1 month prior to the start of study intervention.
• Participant has a clinically significant disease or co-morbidity that may adversely
affect the safe delivery of treatment within this study or make the participant
unsuitable for study participation.
• Participant has psychiatric illness or social situations that would preclude study
compliance.
• Participant has had a major surgical procedure 28 days before start of study
intervention and has not fully recovered.
• Participant has received radiotherapy for locally advanced unresectable or metastatic
gastric or GEJ or metastatic pancreatic adenocarcinoma 14 days prior to start of study
intervention and has NOT recovered from any related toxicity.
• Participant has another malignancy for which treatment is required.
• Participant who has received an CLDN18.2-targeted investigational agent (e.g.,
zolbetuximab or chimeric antigen receptor CLDN18.2-specific T cells) prior to first
dose of study intervention administration is not eligible for dose escalation cohorts.
However, a participant who has received an CLDN18.2-targeted investigational agent
greater than 28 days or 5 half-lives (whichever is longer) prior to first dose study
intervention administration is eligible for dose expansion cohorts only, with the
exception of participants who have experienced Grade >= 3 gastrointestinal (GI)
toxicity after receiving an CLDN18.2-targeted investigational agent.
• Participant has a history or complication of interstitial lung disease.
Drug: ASP2138
Pancreatic Adenocarcinoma, Gastric Adenocarcinoma, Other Digestive Organ, Pancreas, Stomach, Small Intestine, Gastroesophageal Junction (GEJ) Adenocarcinoma
Vincristine Sulfate Liposome Injection (Marqibo®) in Combination With UK ALL R3 Induction Chemotherapy for Children, Adolescents, and Young Adults With Relapsed ALL
This is a pilot study utilizing Marqibo® (vincristine sulfate liposome injection) combined
with dexamethasone, mitoxantrone and asparaginase (UK ALL R3) for relapsed acute
lymphoblastic leukemia (ALL).
Inclusion Criteria
Age
-Patients must be ≥ 1 and ≤ 21 years of age at the time of enrollment.
Diagnosis
• Cohort A: Patients must have a diagnosis of acute lymphoblastic leukemia (ALL) or
mixed phenotypic acute leukemia with ≥ 5% blasts in the bone marrow (M2 or M3), with
or without extramedullary disease) or a diagnosis of lymphoblastic lymphoma.
• Cohorts B & C: Patients must have a diagnosis of acute lymphoblastic leukemia (ALL),
lymphoblastic lymphoma, or mixed phenotypic acute leukemia with any level of
detectable disease (minimal residual disease level acceptable) with or without
extramedullary disease
Performance Level -Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for
patients ≤ 16 years of age.
Prior Therapy
• Patients must have recovered from the acute toxic effects (≤ Grade 2 or baseline) of
all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study,
unless otherwise specified. Subjects with disease related cytopenias will be eligible.
• Patients must have relapsed or refractory disease after attaining at least a first
remission. They may be in first to third relapse..
• Patients with Philadelphia chromosome t(9;22) positive disease must have received at
least two prior tyrosine kinase inhibitors.
• Patients who have experienced their relapse after a Hematopoietic stem cell
transplantation (HSCT) are eligible, provided they have no evidence of
graft-versus-host disease (GVHD) and are at least 100 days post-transplant at the time
of enrollment.
• Prior anthracycline lifetime cumulative exposure: Patients must have less than 320
mg/m2 (or 400 mg/m2 if prior cardioprotection) lifetime exposure of anthracycline
chemotherapy.
1. Cohort A: Patients must have less than 320 mg/m2 (or 400 mg/m2 if prior
cardioprotection) lifetime exposure of anthracycline chemotherapy (See Appendix 2
for anthracycline calculation worksheet).
2. Cohorts B & C: There is no limit on prior anthracycline exposure.
• Hematopoietic growth factors: It must have been at least seven days since the
completion of therapy with granulocyte colony-stimulating factor (GCSF) or other
growth factors at the time of enrollment. It must have been at least 14 days since the
completion of therapy with pegfilgrastim (Neulasta®).
• Biologic anti-neoplastic agents: At least seven days after the last dose of a biologic
agent. For agents that have known adverse events occurring beyond seven days after
administration, this period must be extended beyond the time during which adverse
events are known to occur. The duration of this interval must be discussed with the
study chair or vice chair.
• Monoclonal antibodies: At least three half-lives (or 30 days—whichever is longer) of
the antibody must have elapsed after the last dose of monoclonal antibody. (e.g.,
Rituximab = 66 days, Epratuzumab = 69 days)
• Immunotherapy: At least 30 days after the completion of any type of immunotherapy,
e.g. tumor vaccines, chimeric antigen receptor T-cells.
• Recent prior chemotherapy: At least 10 days after standard vincristine and the
completion of any type of chemotherapy induction regimen. At least 3 weeks after
radiation therapy. At least 30 days after the completion of any investigational
neoplastic agent is also required. An investigational agent is defined as any drug
that is not approved and licensed for sale by the FDA for institutions in the United
States, by Health Canada for institutions in Canada and by The Therapeutic Goods
Administration for institutions in Australia.
Exceptions:
• There is no time restriction in regard to prior intrathecal chemotherapy provided
there is complete recovery from any acute toxic effects of such; it is allowable to
enroll a patient that has received IT Cytarabine (ARA-C), IT Methotrexate (MTX) or
triple IT therapy within 14 days of enrollment as part of their evaluation to diagnose
disease relapse. The IT therapy given within 14 days of initiation of protocol
specified chemotherapy, may substitute for the day 1 IT in cohorts A and B
• Subjects with rapidly progressive disease may receive hydroxyurea until they begin
study therapy;
• Patients who relapse while on maintenance-type ALL therapy or are receiving
maintenance therapy for disease stabilization will not require a wash-out period
before entry into this study. However, there must be at least 10 days after any dose
of standard vincristine.
Renal and Hepatic Function
• Renal function: Patient's serum creatinine must be ≤ 1.5 x institutional upper limit
of normal (ULN) according to age. If the serum creatinine is greater than 1.5 times
normal, the patient must have a calculated creatinine clearance or radioisotope
glomerular filtration rate (GFR) ≥ 70milliliter/min/1.73m2. Alternatively, a 24-hour
creatinine clearance may also be used.
• Hepatic function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
must be < 5 x institutional upper limit of norm ULN. Total bilirubin must be ≤ 1.5 x
ULN (except in the case of subjects with documented Gilbert's disease ≤ 5 × ULN).
Cardiac Function
-Patients must have a shortening fraction ≥ 27% or an ejection fraction ≥ 55% by
echocardiogram, cardiac MRI or multigated acquisition scan (MUGA).
Reproductive Function
• Female patients must not be pregnant and those of childbearing potential must have a
negative urine or serum pregnancy test confirmed within one week prior to enrollment.
• Female patients with infants must agree not to breastfeed their infants while on this
study.
• Male and female patients of childbearing potential must agree to use an effective
method of contraception during the study.
Exclusion Criteria
Patients will be excluded if they have isolated testicular disease.
Patients will be excluded if they have previously received Marqibo®.
Patients will be excluded if they have a known allergy to any of the drugs used in the
study, with the exception that patients with an allergy to PEG-asparaginase who can receive
Erwinia asparaginase are eligible. Patients unable to receive any formulation of
asparaginase may only enroll on cohort C
Patients will be excluded if they have active, uncontrolled systemic fungal, bacterial,
viral or other infection despite appropriate antibiotics or other treatment.
Patients who require azole antifungal agents will be excluded. Azoles must be discontinued
at least one week prior to the start of Marqibo®.
Patients will be excluded if there is a plan to administer non-protocol chemotherapy,
radiation therapy, another investigational agent or immunotherapy during the study period.
Patients with pre-existing, persistent grade 2 or greater sensory or motor neuropathy from
any cause will be excluded.
Patients will be excluded if they have, significant concurrent disease, illness,
psychiatric disorder or social issue that would compromise patient safety or adherence with
the protocol treatment or procedures or interfere with consent, study participation, follow
up, or interpretation of study results.Patients with Down syndrome will not be eligible for
enrollment on Cohort A
Patients with a known history of human immunodeficiency virus (HIV) will will be excluded
due to the increased risk of complications such as severe infection and unknown interaction
of Marqibo® with antiretroviral drugs.
Active hepatitis B or C infection as defined by seropositive for hepatitis B (hepatitis B
surface antigen (HBsAg)) or hepatitis C and elevated liver transaminases (defined as above
the ULN per the institution normal ranges).
Crizotinib in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Removed by Surgery and ALK Fusion Mutations (An ALCHEMIST Treatment Trial)
This randomized phase III trial studies how well crizotinib works in treating patients with
stage IB-IIIA non-small cell lung cancer that has been removed by surgery and has a mutation
in a protein called anaplastic lymphoma kinase (ALK). Mutations, or changes, in ALK can make
it very active and important for tumor cell growth and progression. Crizotinib may stop the
growth of tumor cells by blocking the ALK protein from working. Crizotinib may be an
effective treatment for patients with non-small cell lung cancer and an ALK fusion mutation.
• Patients must have undergone complete surgical resection of their stage IB (>= 4 cm),
II, or non-squamous IIIA NSCLC per American Joint Committee on Cancer (AJCC) 7th
edition and have had negative margins; N3 disease is not allowed
• Baseline chest computed tomography (CT) with or without contrast must be performed
within 6 months (180 days) prior to randomization to ensure no evidence of disease; if
clinically indicated additional imaging studies must be performed to rule out
metastatic disease
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Patients must be registered to the ALCHEMIST-SCREEN (ALLIANCE A151216) trial prior to
randomization
• Positive for translocation or inversion events involving the ALK gene locus (e.g.
resulting in echinoderm microtubule associated protein like 4 [EML4]-ALK fusion) as
determined by the Vysis Break Point fluorescence in situ hybridization (FISH) assay
and defined by an increase in the distance between 5? and 3? ALK probes or the loss of
the 5? probe; this must have been performed:
• By a local Clinical Laboratory Improvement Amendments (CLIA) certified
laboratory: report must indicate the results as well as the CLIA number of the
laboratory which performed the assay; tissue must be available for submission for
central, retrospective confirmation of the ALK fusion status via ALCHEMIST-SCREEN
(ALLIANCE A151216) OR
• Patient registered to and the ALK fusion status performed centrally on the
ALCHEMIST-SCREEN (ALLIANCE A151216)
• Women must not be pregnant or breast-feeding
• All females of childbearing potential must have a blood or urine pregnancy test within
72 hours prior to randomization to rule out pregnancy; a female of childbearing
potential is any woman, regardless of sexual orientation or whether they have
undergone tubal ligation, who meets the following criteria: 1) has not undergone a
hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal
for at least 24 consecutive months (i.e., has had menses at any time in the preceding
24 consecutive months)
• Women of childbearing potential and sexually active males must be strongly advised to
practice abstinence or use an accepted and effective method of contraception
• Patients must NOT have uncontrolled intercurrent illness including, but not limited
to, serious ongoing or active infection, symptomatic congestive heart failure,
unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric
illness/social situations that would limit compliance with study requirements
• No known interstitial fibrosis or interstitial lung disease
• No prior treatment with crizotinib or another ALK inhibitor
• No ongoing cardiac dysrhythmias of grade >= 2 National Cancer Institute (NCI) Common
Terminology Criteria for Adverse Events (CTCAE) version 4.0, uncontrolled atrial
fibrillation (any grade), or corrected QT (QTc) interval > 470 msec
• No use of medications, herbals, or foods that are known potent cytochrome P450,
subfamily 3A, polypeptide 4 (CYP3A4) inhibitors or inducers, included but not limited
to those outlined
• Patients must be adequately recovered from surgery at the time of randomization
• The minimum time requirement between date of surgery and randomization must be at
least 4 weeks (28 days)
• The maximum time requirement between surgery and randomization must be:
• 3 months (90 days) if no adjuvant chemotherapy was administered
• 8 months (240 days) if adjuvant chemotherapy was administered
• 10 months (300 days) if adjuvant chemotherapy and radiation therapy were
administered
• Patients must have completed any prior adjuvant chemotherapy or radiation therapy 2 or
more weeks (6 or more weeks for mitomycin and nitrosoureas) prior to randomization and
be adequately recovered at the time of randomization
• NOTE: Patients taking low dose methotrexate for non-malignant conditions and
other cytotoxic agents for non-malignant conditions are allowed to continue
treatment while on study
• NOTE: Neo-adjuvant chemotherapy or radiation therapy for the resected lung cancer
is not permitted
• Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) =< 2.5
x upper limit of normal (ULN)
• Total serum bilirubin =< 1.5 x ULN
• Absolute neutrophil count (ANC) >= 1500/mm^3
• Platelets >= 30,000/mm^3
• Hemoglobin >= 8.0 g/dL
• Serum creatinine =< 2 x ULN
• Prior to randomization patients with any non-hematologic toxicity from surgery,
chemotherapy, or radiation must have recovered to grade =< 1 with the exception of
alopecia and the criteria outlined
• Patients must not have any history of locally advanced or metastatic cancer requiring
systemic therapy within 5 years from randomization, with the exception of in-situ
carcinomas and non-melanoma skin cancer; patients must have no previous primary lung
cancer diagnosed concurrently or within the past 2 years
• Patients may not be receiving any other investigational agents while on study
Feasibility Study Using Imaging Biomarkers in Lung Cancer
The purpose of this research study is to develop a method of using magnetic resonance imaging
(MRI) to evaluate solitary pulmonary nodules (mass in the lung smaller than 3 centimeters). A
pulmonary nodule is a mass or growth on the lung. An MRI is a scanning device that uses
magnets to make images (pictures) of the body. This study is being done to determine what
series of reactions (metabolic pathways) pulmonary nodules use as they burn sugar as fuel for
growth. The manner in which the tumor burns (metabolizes) sugar for fuel is being
investigated by using a natural, slightly modified, sugar solution (13C-glucose) and studying
a small sample of the tumor once it is removed at the time of surgery.
• Subjects of all races and ethnic origins over 18 years of age will be recruited.
• Patients must have suspicious or known to be malignant solitary pulmonary nodule,5cm
or less in size.
Exclusion Criteria:
• Patients with a contraindication to MRI examinations will be excluded from this study.
Contraindications to MRI examinations include:
• Medically unstable
• Heart failure
• Unstable angina
• Child bearing
• Lactating
• Not a surgical candidate
• Any contraindication per MRI Screening Form (Appendix A attached). This is the same
form used in clinical practice at UT Southwestern.
• Titanium implants, pacemakers
• Poorly controlled diabetes
• Body weight greater than 300 pounds
• Claustrophobic
• Since each patient is receiving a gadolinium based contrast agent intravenously:
• eGFR < 45 mL/min/1.73m2
• Sickle cell disease
• Hemolytic anemia
• Status post radical prostatectomy for histologically confirmed adenocarcinoma of the
prostate
• pathologically confirmed T1-T3 disease
• no sign of lymph node or metastatic disease
• pT1-pT3pNxMx patients in whom standard NCCN or AUA guidelines would suggest are at low
risk for pelvic lymph node or metastatic disease and who would not require
confirmatory imaging for metastatic disease. This includes patients with Gleason 6 or
7(T2 disease) and PSA less than 20.
• Eastern Cooperative Oncology Group(ECOG) status 0-2
• adequate renal and liver function as well as bone marrow reserve (measured serum
creatinine <2mg/dl, bilirubin ≤ 1.5 mg/dl, ANC ≥ 1.5 x 10 (3) uL, platelets ≥ 50 x
K/uLL, and hemoglobin ≥ 10 g/dL)
• 30-80 y/o at time of diagnosis with a life expectancy of >= 3 yrs
• focally positive surgical margins are permitted
• no plan to receive adjuvant hormone or radiation therapy
• PSA at the time of enrollment must be undetectable
• life expectancy of 3 years
Exclusion Criteria:
• must not have exceeded 3 months from time of surgery to enrollment into study
• T3b or T4 or node positive disease
• macroscopic residual disease after surgery
• hormone therapy before surgery
• history of gallbladder problems or gallstones, or biliary obstruction, unless patient
had cholecystectomy
• radiation therapy as primary treatment after surgery
• INR value greater than 1.5
• AST/ALT are equal or greater than 2 times the upper limit of normal
• antiplatelet or anticoagulant agents- patients taking 81mg of Aspirin will be allowed
with close observation
• history of gastric or duodenal ulcers or untreated hyperacidity syndromes
• patients who are currently taking curcumin and are unwilling to stop or plan to take
curcumin during the study
Drug: Curcumin, Drug: placebo
Prostate Cancer, Prostate
prostate cancer, radical prostatectomy
UT Southwestern; Parkland Health & Hospital System
• Age > 18 years.
• ECOG performance status (PS) 0, 1, or 2.
• Radiographic findings consistent with non-small cell lung cancer, including lesions
with ground glass opacities with a solid component of 50% or greater. Those with
ground glass opacities and <50% solid component will be excluded.
• The primary tumor in the lung must be biopsy confirmed non-small cell lung cancer
within 180 days prior to randomization.
• Tumor ≤ 4 cm maximum diameter, including clinical stage IA and selected IB by PET/CT
scan of the chest and upper abdomen performed within 180 days prior to randomization.
Repeat imaging within 90 days prior to randomization is recommended for re-staging but
is not required based on institutional norms.
• All clinically suspicious mediastinal N1, N2, or N3 lymph nodes (> 1 cm short-axis
dimension on CT scan and/or positive on PET scan) confirmed negative for involvement
with NSCLC by one of the following methods: mediastinoscopy, anterior mediastinotomy,
EUS/EBUS guided needle aspiration, CT-guided, video-assisted thoracoscopic or open
lymph node biopsy within 180 days of randomization.
• Tumor verified by a thoracic surgeon to be in a location that will permit sublobar
resection.
• Tumor located peripherally within the lung. NOTE: Peripheral is defined as not
touching any surface within 2 cm of the proximal bronchial tree in all directions. See
below. Patients with non-peripheral (central) tumors are NOT eligible.
• No evidence of distant metastases.
• Availability of pulmonary function tests (PFTs •spirometry, DLCO, +/- arterial blood
gases) within 180 days prior to registration. Patients with tracheotomy, etc, who are
physically unable to perform PFTs (and therefore cannot be tested for the Major
criteria in 3.1.11 below) are potentially still eligible if a study credentialed
thoracic surgeon documents that the patient's health characteristics would otherwise
have been acceptable for eligibility as a high risk but nonetheless operable patient
(in particular be eligible for sublobar resection).
• Patient at high-risk for surgery by meeting a minimum of one major criteria or two
minor criteria
• Major Criteria
• FEV1 ≤ 50% predicted (pre-bronchodilator value)
• DLCO ≤ 50% predicted (pre-bronchodilator value)
• Minor Criteria
• Age ≥75
• FEV1 51-60% predicted (pre-bronchodilator value)
• DLCO 51-60% predicted (pre-bronchodilator value)
• Pulmonary hypertension (defined as a pulmonary artery systolic pressure greater
than 40mm Hg) as estimated by echocardiography or right heart catheterization
• Study credentialed thoracic surgeon believes the patient is potentially operable
but that a lobectomy or pneumonectomy would be poorly tolerated by the patient
for tangible or intangible reasons. The belief must be declared and documented in
the medical record prior to randomization.
• Poor left ventricular function (defined as an ejection fraction of 40% or less)
• Resting or Exercise Arterial pO2 ≤ 55 mm Hg or SpO2 ≤ 88%
• pCO2 > 45 mm Hg
• Modified Medical Research Council (MMRC) Dyspnea Scale ≥ 3.
• No prior intra-thoracic radiation therapy for previously identified intra-thoracic
primary tumor (e.g. previous lung cancer) on the ipsilateral side. NOTE: Previous
radiotherapy as part of treatment for head and neck, breast, or other non-thoracic
cancer is permitted so long as possible radiation fields would not overlap. Previous
chemotherapy or surgical resection specifically for the lung cancer being treated on
this protocol is NOT permitted.
• No prior lung resection on the ipsilateral side.
• Non-pregnant and non-lactating. Women of child-bearing potential must have a negative
urine or serum pregnancy test prior to registration. Peri-menopausal women must be
amenorrheic > 12 months prior to registration to be considered not of childbearing
potential.
• No prior invasive malignancy, unless disease-free for ≥ 3 years prior to registration
(exceptions: non-melanoma skin cancer, in-situ cancers).
• Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
• evidence of distant metastases
• prior intra-thoracic radiation therapy. NOTE: Previous radiotherapy as part of
treatment for head and neck, breast, or other non-thoracic cancer is permitted so long
as possible radiation fields would not overlap. Previous chemotherapy or surgical
resection specifically for the lung cancer being treated on this protocol is NOT
permitted. No prior lung resection on the ipsilateral side.
• pregnant and lactating women
• prior invasive malignancy, unless disease-free for ≥ 3 years prior to registration
(exceptions: non-melanoma skin cancer, in-situ cancers).
Phase 1/2a Evaluation of Adding AL3818 to Standard Platinum-Based Chemotherapy in Subjects With Recurrent or Metastatic Endometrial, Ovarian, Fallopian, Primary Peritoneal or Cervical Carcinoma (AL3818-US-002) (AL3818)
This trial is a Phase 1b/2a trial designed to evaluate the safety and efficacy of adding oral
AL3818 to standard platinum-based chemotherapy concurrently and continued as a maintenance
therapy for up to 12 months.
• Female ≥ 18 years
• Previously histologically proven diagnosis of
a. Endometrial Cancer: recurrent or persistent endometrial carcinoma refractory to
conventional therapy or established treatments with the following histologic
epithelial cell types i. Endometrioid adenocarcinoma, serous adenocarcinoma,
undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma,
adenocarcinoma not otherwise specified, mucinous adenocarcinoma, squamous cell
carcinoma, and transitional cell carcinoma b. Ovarian Cancer: recurrent or persistent
ovarian or primary peritoneal cancer refractory to established treatments with the
following histologic epithelial cell types i. Endometrioid adenocarcinoma, serous
adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed
epithelial carcinoma, adenocarcinoma not otherwise specified.
c. Cervical cancer: squamous cell carcinoma of the cervix refractory to conventional
therapy or established treatments with the following histologic epithelial cell types:
i. Squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma Measurable
disease defined as at least one lesion that can be accurately measured in at least one
dimension (longest dimension to be recorded). Each lesion must be ≥ 20mm when measured
by conventional techniques, including palpation, plain x-ray, CT, and MRI or ≥ 10mm
when measured by spiral CT.
• Life expectancy ≥ 3 months
• Able to take orally administered study medication
• Must sign approved informed consent and authorization permitting release of personal
health information.
• Patient must have adequate:
1. Bone marrow function: absolute neutrophil count (ANC) ≥ 1,500/mm^3, equivalent to
Common Toxicity Criteria (CTC) grade 1, platelets ≥ 100,000/mm^3
2. Renal function: creatinine ≤ 1.5 x institutional upper limit normal (ULN), CTC
grade 1. Note: If creatinine is > 1.5 x ULN, creatinine clearance must be > 50
mL/min.
3. Hepatic function: bilirubin ≤ 1.5 x ULN (CTC grade 1) or ≤ 3.0 x ULN for subjects
with Gilbert Syndrome; AST and ALT ≤ 3.0 ×ULN.
4. Coagulation profile: PT such that international normalized ratio (INR) is ≤ 1.55
(or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of
therapeutic warfarin or low molecular weight heparin) and a PTT < 1.2 times
control.
5. ECOG performance ≤ 2
• Patient of child-bearing potential must agree to use contraceptive measures starting 1
week before the administration of the first dose of AL3818 until 4 weeks after
discontinuing study drug and have a negative serum pregnancy test prior to study entry
and cannot be lactating.
• Ability and willingness to comply with the study protocol for the duration of the
study and with follow-up procedures.
Exclusion Criteria:
• Patients with serious, non-healing wound, ulcer or bone fracture.
• Patients with active bleeding or pathologic conditions that carry high risk of
bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major
vessels.
• Patient with history or evidence upon physical examination of CNS disease, including
primary brain tumor, seizures not controlled with standard medical therapy, any brain
metastases or history of cerebrovascular accident (CVA, stroke) transient ischemic
attack (TIA) or subarachnoid hemorrhage within 6 months of the first date of treatment
on this study.
a. Patients with metastatic CNS tumors may participate in this trial, if the patient
is > 4 weeks from therapy completion (including radiation and/or surgery), is
clinically stable at the time of study entry and is not receiving corticosteroid
therapy.
• Patients with proteinuria: patients discovered to have a urine protein of 1+ on
dipstick or ≥ 30 mg/dl at baseline should undergo a 24-hour urine collection, which
must be an adequate collection and must demonstrate < 1000 mg protein/24 hours to
allow participation in the study.
• Patients with clinically significant cardiovascular disease including uncontrolled
hypertension, myocardial infarction or unstable angina within 6 months prior to
registration. New York Heart Association (NYHA) Grade II or greater congestive heart
failure, Serious cardiac arrhythmia requiring medication, Grade II or greater
peripheral vascular disease.
• Patients who are pregnant or nursing.
• Women of childbearing potential who are unable to use contraceptive measures during
study therapy and for at least 3 months after completion of AL3818 therapy.
• Patients with uncontrolled hypokalemia, hypomagnesaemia, and/or hypocalcaemia.
• Hemoptysis within 3 months prior to first scheduled dose of AL3818.
• Patients with acute or chronic liver disease, active hepatitis A or B with known
cirrhosis or liver dysfunction.
• Cytotoxic chemotherapy, immunotherapy, or radiotherapy within 4 weeks (6 weeks in
cases of mitomycin C, nitrosourea, lomustine) prior to first scheduled dose of AL3818
or a major surgical procedure within 28 days or minor surgical procedure performed
within 7 days prior to first scheduled dose of AL3818.
• Concomitant treatment with strong inhibitors or inducers of CYP3A4, CYP2C9 and CYP2C19
who cannot be switched to other alternative medications .
• Known history of human immunodeficiency virus infection (HIV).
• Subjects with active bacterial infections (other than uncomplicated urinary tract
infection) and/or receiving systemic antibiotics.
• Patients with other invasive malignancies, with the exception of non-melanoma skin
cancer, who had (or have) any evidence of other cancer present within the last 5 years
or whose previous cancer treatment contraindicates this protocol therapy.
• History of non-malignant GI bleeding, gastric stress ulcerations, or peptic ulcer
disease within the past 3-months that in the opinion of the investigator may place the
patient at risk of side effects on an anti-angiogenesis product.
• History of significant vascular disease (e.g. aortic aneurysm, aortic dissection).
• Intra-abdominal abscess within the last 3 months.
• Pre-existing uncontrolled hypertension as documented by 2 baseline BP readings taken
at least one hour apart, defined as systolic bloodpressure (BP) >160 mm Hg or
diastolic BP > 90 mm Hg pressure.
• QTcF>470 msec on screening ECG.
• A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family
history of Long QT Syndrome).
• The use of concomitant medications that prolong the QT/QTc interval. Baseline
echocardiogram (within 2 months) with left ventricular ejection fraction (LVEF) < 50%.
• History of difficulty swallowing, malabsorption, active partial or complete bowel
obstruction, or other chronic gastrointestinal disease or condition that may hamper
compliance and/or absorption of AL3818.
• History of pancreatitis and/or renal disease or pancreatitis that includes
histologically confirmed glomerulonephritis, biopsy proven tubulointerstitial
nephritis, crystal nephropathy, or other renal insufficiencies.
• Treatment with an investigational agent within the longest time frame of either 5
half- lives or 30 days of initiating study drug.
• Known recreational substance abuse.
• Known hypersensitivity to AL3818 or components of the formulation.
Web-Based Physical Activity Intervention in Improving Long Term Health in Children and Adolescents With Cancer
This randomized clinical phase III trial studies how well web-based physical activity
intervention works in improving long term health in children and adolescents with cancer.
Regular physical activity after receiving treatment for cancer may help to maintain a healthy
weight and improve energy levels and overall health.
• All cancer cases with an International Classification of Diseases for Oncology (ICD)-O
histologic behavior code of two "2" (carcinoma in situ) or three "3" (malignant), in
remission
• Patient must have completed curative therapy (surgery and/or radiation and/or
chemotherapy) within the past 12 months at a Childrens Oncology Group (COG)
institution
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1, or 2; use Lansky for patients =< 16 years of age
• At the time of consent, patient or parent/guardian reports less than 420 minutes of
moderate to vigorous physical activity over the last week
• Patient and at least one parent/guardian are able to read and write English, Spanish,
and/or French; at least 1 parent/guardian must be able to read and write English,
Spanish, and/or French in order to assist the patient with using their physical
activity tracking device account
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Exclusion Criteria:
• Patients with previous hematopoietic stem cell transplant (HSCT)
• Patients with significant concurrent disease, illness, psychiatric disorder or social
issue that would compromise patient safety or compliance with protocol therapy, or
interfere with consent, study participation, follow up, or interpretation of study
results
• Female patients who are pregnant are not eligible; women of childbearing potential
require a negative pregnancy test
• Female patient who is postmenarcheal and has not agreed to use an effective
contraceptive method (including abstinence) for the duration of study participation
• Patients with a cognitive, motor, visual or auditory impairment that prevents computer
use (e.g. unresolved posterior fossa syndrome) are not eligible
1. Age ≥ 18 years.
2. ECOG Performance Score of 2 or better/Karnofsky Performance score of 50-60 or better.
3. Biopsy-proven non-hematopoietic malignancy, except for germ cell cancer. Small cell
lung carcinoma is eligible for this study.
4. Six or more metastases on diagnostic or treatment planning imaging, which include
either CT Brain (with contrast) or MR Brain (with or without contrast) imaging.
5. Largest tumor <= 4 cm.
6. No prior SRS to the lesions which will be treated on protocol.
7. 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.
Should a woman become pregnant or suspect she is pregnant while participating in this
study, she should inform her treating physician immediately.
A female of child-bearing potential is any woman (regardless of sexual orientation,
marital status, 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).
8. Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
1. Prior whole brain radiotherapy
2. Patients with leptomeningeal metastasis. (NOTE: For the purposes of exclusion, LMD is
a clinical diagnosis, defined as positive CSF cytology and/or equivocal radiologic or
clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms
in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to
have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can
adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic
or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement
(MRI) would not be considered to have LMD. In that patient, CSF sampling is not
required to formally exclude LMD, but can be performed at the investigator's
discretion based on level of clinical suspicion.)
3. Patients with life expectancy < 4 months.
4. Psychiatric illness/social situations that, in the opinion of the investigator, would
limit compliance with study requirements.
5. Subjects must not be pregnant or nursing due to the potential for congenital
abnormalities and the potential of this regimen to harm nursing infants.
Radiation: Stereotactic Radiosurgery
Brain Metastases, Brain and Nervous System
UT Southwestern; Parkland Health & Hospital System
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.
Prostate Oncologic Therapy While Ensuring Neurovascular Conservation (POTEN-C) (POTEN-C)
Reduction of dose to or 'sparing' of neurovascular structures during stereotactic ablative
body radiotherapy (SAbR) for localized prostate cancer will improve retention of sexual
potency, while retaining excellent oncologic control and other secondary health-related
quality of life (HRQOL) endpoints.
Primary Objectives:
• To compare the decline in patient health-related quality of life (HRQOL) instrument-defined
erectile dysfunction following stereotactic ablative body radiotherapy (SAbR) with or without
neurovascular sparing
Secondary Objectives:
- Assess acute (within 3 months of treatment) and chronic (>3 months after treatment) SAbR
related GU and GI toxicities, as well as serial impact on HRQOL metrics over time
- Assess biochemical progression free survival, local recurrence, distant recurrence, and
survival
- Evaluate simplified 'practical' secondary HRQOL sexual potency endpoints that can be
compared to prior literature.
Exploratory Objectives:
- Evaluate feasibility of MRI BOLD/TOLD to be integrated as hypoxia monitoring sequences
to standard already planned diagnostic and/or treatment planning MRI on the study in
five patient pilot.
- Evaluate quality of spacer placement and its effect on dose to neurovascular structures
- Evaluate rate local recurrence in the area of sparing adjacent to the neurovascular
elements by biopsy in those with biochemical progression.
1. Age ≥ 18 years.
2. Appropriate staging studies identifying patient as AJCC 7th edition clinical stage T1
(a, b, or c) or T2 (a, b, or c) adenocarcinoma of the prostate gland. The patient
should not have direct evidence of regional or distant metastases after appropriate
staging studies. See Appendix I for details on AJCC 7th Edition staging criteria.
Histologic confirmation of cancer will be required by biopsy performed within 12
months of registration. T-staging may be assessed by multi-parametric imaging alone if
digital rectal examination was deferred.
3. The patient's Zubrod performance status must be 0-2 (see Appendix II for definition).
4. The Gleason summary score should be less than or equal to 7 [Grade group 1 (Gleason
3+3=6), group 2 (Gleason 3+4=7), and group 3 (Gleason 4+3=7) are allowed]. See
Appendix III for details on definitions. While a template biopsy is recommended, it is
not required in the case of MRI fusion biopsy performed on all dominant MR lesions
(defined as PIRADS v2 4-5).
5. Baseline AUA symptom score ≤19 (see Appendix IV for questionnaire) without need for
maximum medical therapy (specifically, not on tamsulosin 0.8mg daily).
6. EPIC sexual domain composite score 60-100 (see Appendix V).
7. Multi-parametric MRI evaluation of the prostate is required for this study within 12
months of registration. Gross radiographic disease on MRI (defined as PIRADS v2 score
3-5) must be > 5mm at minimum distance from at least one side's neurovascular bundle,
which is typically the closest of the neurovascular elements to the prostate.
8. The serum PSA should be less than or equal to 20 ng/ml within 90 days of registration.
-Study entry PSA must not be obtained during the following time frames: (1) 10-day
period following prostate biopsy; (2) following initiation of ADT or anti-androgen
therapy; (3) within 30 days after discontinuation of finasteride; (4) within 90 days
after discontinuation of dutasteride; (5) within 5 days of a digital rectal
examination (which is not a required exam on the protocol).
9. Ultrasound or MRI based volume estimation of prostate gland ≤ 80 grams. Cytoreduction
therapy (finasteride or dutasteride only) may be considered for those with >60 gram
size.
10. All patients must be willing and capable to provide informed consent to participate in
the protocol within the 30 days prior to registration.
Exclusion Criteria:
1. Subjects with clinical (digital rectal examination) evidence of extraprostatic
extension (T3a) or seminal vesicle involvement (T3b). MRI evidence of
equivocal/potential but not definite extraprostatic extension is allowed, as long as
it is unilateral and not on the side of the gland proposed for neurovascular element
sparing. In equivocal cases of potential extracapsular extension on MRI only,
discretion is left to the treating physician.
2. MRI evidence of gross disease (defined as PIRADS v2 score 3-5 lesions) ≤5mm of BOTH
neurovascular bundles, which are the most proximate of the neurovascular elements
planned for sparing on this protocol.
3. Patients with all three intermediate risk factors (PSA >10 and ≤ 20, Gleason 7,
clinical stage T2b-T2c) who ALSO have ≥50% of the number of their template biopsy
cores positive for cancer are ineligible.
4. Inability to undergo multi-parametric MRI.
5. Evidence of metastatic disease. Note bone scan is not required for this study given
the low-intermediate NCCN risk cohort to be enrolled.
6. Evidence of clinical nodal involvement of the pelvis. Biopsy is required for lymph
nodes over ≥1.5cm in short-axis measured size.
7. No currently active ADT or anti-androgen therapy at time of registration is allowed.
Further, no more than 3 cumulative months of prior ADT or anti-androgen therapy is
allowed. If either has been used by the patient, there must be a demonstration of
testosterone recovery (>50ng/dL serum blood level), EPIC sexual domain score ≥60, and
at least 1 month between demonstration of testosterone recovery and study registration
(any one measurement of testosterone recovery suffices).
8. Testosterone ≤ 50 ng/dL (any one measurement >50 ng/dL suffices for inclusion) within
90 days of study entry.
9. Subjects who have had previous pelvic radiotherapy or have had chemotherapy or surgery
for prostate cancer.
10. Subjects who have plans to receive other concomitant or post treatment adjuvant
antineoplastic therapy while on this protocol including surgery, cryotherapy,
conventionally fractionated radiotherapy, hormonal therapy, or chemotherapy given as
part of the treatment of prostate cancer.
11. Subjects who have undergone previous transurethral resection of the prostate (TURP)
within 1 year of enrollment or ablative procedures to the prostate for benign
prostatic hyperplasia or other conditions (i.e. cryotherapy, HIFU).
12. Subjects who have baseline severe urinary symptoms, as defined by AUA symptom score
>19 (alpha-blocker medication allowed except if taking tamsulosin 0.8mg daily at
baseline which indicates compensated severe symptoms and also can affect sexual
function).
13. Subjects who have a history of significant psychiatric illness that would confound
informed consent.
14. Severe, active co-morbidity, defined as follows:
1. Unstable angina and/or congestive heart failure requiring hospitalization within
the last 6 months
2. Myocardial infarction within the last 6 months
3. Acute bacterial or fungal infection requiring intravenous antibiotics at time of
registration
4. Patients with active inflammatory colitis (including Crohn's Disease and
ulcerative colitis) currently requiring systemic steroids and/or systemic
immunosuppression are not eligible.
15. Subjects with a known allergy to polyethylene glycol hydrogel (rectal spacer material)
or contraindication to spacer products (SpaceOAR).
16. Subjects with uncontrolled coagulation disorder which cannot be controlled with
anticoagulants.
17. Men active with partners of reproductive potential who do not agree that they will use
an effective contraceptive method during treatment and 6 months after treatment.
18. Men who require erectile function medication or aid to achieve an erection sufficient
for intercourse. Ability to achieve erection sufficient for intercourse without
medication or aid at least once time in the month prior to registration is sufficient
for inclusion.
19. Men who have clinically significant penile malformation (i.e. Peyronie's disease) or
history of penile implantation are excluded.
20. If DRE is performed, patient may not have palpable disease on side of gland to be
planned for neurovascular sparing. Given the poor accuracy of DRE, such a finding
should be confirmed by MRI and/or biopsy to harbor actual disease before excluding a
patient on this basis.
Digital Tomosynthesis Mammography and Digital Mammography in Screening Patients for Breast Cancer
This randomized phase III trial studies digital tomosynthesis mammography and digital
mammography in screening patients for breast cancer. Screening for breast cancer with
tomosynthesis mammography may be superior to digital mammography for breast cancer screening
and may help reduce the need for additional imaging or treatment.
• Women of childbearing potential must not be known to be pregnant or lactating
• Patients must be scheduled for, or have intent to schedule, a screening mammogram
• Patients must be able to tolerate digital breast tomosynthesis and full-field digital
mammographic imaging required by protocol.
• Patients must be willing and able to provide a written informed consent
• Patients must not have symptoms or signs of benign or malignant breast disease (eg,
nipple discharge, breast lump) warranting a diagnostic rather than a screening
mammogram, and/or other imaging studies (eg, sonogram); patients with breast pain are
eligible as long as other criteria are met
• Patients must not have had a screening mammogram within the last 11 months prior to
date of randomization
• Patients must not have previous personal history of breast cancer including ductal
carcinoma in situ
• Patients must not have breast enhancements (e.g., implants or injections)
• ANNUAL SCREENING REGIMEN ELIGIBILITY CHECK
• To be eligible for inclusion in the annual screening regimen one of the following
three conditions must be met in addition to the eligibility criteria above:
• Patients are pre-menopausal; OR
• Post-menopausal aged 45-69 with any of the following three risks factors:
• Dense breasts (BIRADS density categories c-heterogeneously dense or
d-extremely dense), or
• Family history of breast cancer (first degree relative with breast cancer),
or, positive genetic testing for any deleterious genes that indicate an
increased risk for breast cancer, or
• Currently on hormone therapy; OR
• Post-menopausal ages 70-74 with either of the following two risk factors:
• Dense breasts (BIRADS density categories c-heterogeneously dense or
d-extremely dense), or
• Currently on hormone therapy
• Postmenopausal women are defined as those with their last menstrual period more than
12 months prior to study entry; for the purpose of defining menopausal status for
women who have had surgical cessation of their periods, women who no longer have
menses due to hysterectomy and oophorectomy will be considered postmenopausal; women
who no longer have menses due to hysterectomy without oophorectomy will be considered
premenopausal until age 52 and postmenopausal thereafter
• All other postmenopausal women are eligible for inclusion in the biennial screening
regimen
• For those women who cannot be assigned to annual or biennial screening at the time of
study entry and randomization because they are postmenopausal, have no family history
or known deleterious breast cancer mutation, are not on hormone therapy AND have not
had a prior mammogram, breast density will be determined by the radiologist?s
recording of it at the time of interpretation of the first study screening
examination, either DM or TM; for those who are randomized to TM, radiologists will
assign BI-RADS density through review of the DM or synthetic DM portion of the TM
examination; such women cannot be part of the planned stratification by screening
frequency and are expected to represent far less than 1% of the Tomosynthesis
Mammographic Imaging Screening Trial (TMIST) population
• Breast density will be determined by prior mammography reports, when available; all
other risk factors used to determine patient eligibility for annual or biennial
screening will be determined by subject self-report
Procedure: Digital Mammography, Procedure: Digital Tomosynthesis Mammography, Other: Laboratory Biomarker Analysis
Breast Screening, Breast - Female
Digital Mammography, Breast Tomography, Screening Mammography, TMIST
A Study of Daratumumab Plus Lenalidomide Versus Lenalidomide Alone as Maintenance Treatment in Participants With Newly Diagnosed Multiple Myeloma Who Are Minimal Residual Disease Positive After Frontline Autologous Stem Cell Transplant (AURIGA)
The purpose of this study is to evaluate conversion rate to minimal residual disease (MRD)
negativity following the addition of daratumumab to lenalidomide relative to lenalidomide
alone, when administered as maintenance treatment to anti-cluster of differentiation 38
(CD38) treatment naive participants with newly diagnosed multiple myeloma who are MRD
positive as determined by next generation sequencing (NGS) at screening, following high-dose
therapy (HDT) and autologous stem cell transplant (ASCT).
• Must have newly diagnosed multiple myeloma with a history of a minimum of 4 cycles of
induction therapy, have received high-dose therapy (HDT) and autologous stem cell
transplantation (ASCT) within 12 months of the start of induction therapy, and be
within 6 months of ASCT on the date of randomization
• Must have a very good partial response (VGPR) or better response assessed per
International Myeloma Working Group (IMWG) 2016 criteria at the time of randomization
• Must have archived bone marrow samples collected before induction treatment (that is,
at diagnosis) or before transplant (for example, at the end of induction) or have
existing results on the index multiple myeloma clone based on Adaptive
Biotechnologies' next generation sequencing (NGS)-based minimal residual disease (MRD)
assay. Archived bone marrow samples will be used for calibration of myeloma clonal
cells to facilitate assessment of primary end point by NGS. If an existing result on
index myeloma clone is available from Adaptive Biotechnologies' NGS-based MRD assay,
as part of institutional procedures, an archived bone marrow sample is not required as
long as Adaptive Biotechnologies is able to retrieve historical results on the index
myeloma clone form the clinical database. Any one of the following archived samples
are required: (a) Greater than 1 milliliter (mL) viable frozen bone marrow aspirated
aliquot (preferred) collected in an ethylenediaminetetra-acetic acid (EDTA) tube,
frozen, and stored at a temperature of -80 centigrade (°C), or; (b) Non-decalcified
diagnostic bone marrow aspirate clot sections (block or slides) for MRD assessment:
(i) A formalin fixed paraffin embedded (FFPE) block of bone marrow aspirate clot, or
slides (preferably 5, if available), 5 micrometer each, of non-decalcified bone
marrow, or; (ii) Slides (preferably 5, if available), bone marrow aspirate smear;
(iii) Please note, bone marrow core sections are not acceptable samples for analysis;
(iv) In exceptional circumstances when index myeloma clone cannot be identified from
the archived bone marrow sample, a post-transplant sample can be used to identify
myeloma clone with permission from the sponsor
• Must have residual disease as defined by detectable MRD (Adaptive Biotechnologies' NGS
based MRD assay)
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0,
1, or 2
Exclusion Criteria:
• A history of malignancy (other than multiple myeloma) unless all treatment of that
malignancy was completed at least 2 years before consent and the participant has no
evidence of disease before the of date of randomization. Exceptions are squamous and
basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other
non-invasive lesion that in the opinion of the investigator, with concurrence with the
sponsor's medical monitor, is considered cured with minimal risk of recurrence within
3 years
• Must not have progressed on multiple myeloma (MM) therapy at any time prior to
screening
• Have had prior treatment/therapy with: (a) Daratumumab or any other anti-cluster of
differentiation 38 (CD38) therapies, (b) Focal radiation therapy within 14 days prior
to randomization with the exception of palliative radiotherapy for symptomatic
management but not on measurable extramedullary plasmacytoma. Radiotherapy within 14
days prior to randomization on measurable extramedullary plasmacytoma is not permitted
even in the setting of palliation for symptomatic management, or (c) Plasmapheresis
within 28 days of randomization
• Be exhibiting clinical signs of meningeal or central nervous system involvement due to
multiple myeloma
• Have known chronic obstructive pulmonary disease (COPD) with a forced expiratory
volume in 1 second (FEV1) less than (<) 50 percent (%) of predicted normal
• Have known moderate or severe persistent asthma within the past 2 years or current
uncontrolled asthma of any classification
• Have any of the following: (a) Known history of seropositivity for human
immunodeficiency virus (HIV); (b) Seropositive for hepatitis B (defined by a positive
test for hepatitis B surface antigen [HBsAg]. Participants with resolved infection
(that is, participants who are HBsAg negative but positive for antibodies to hepatitis
B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs])
must be screened using real-time polymerase chain reaction (PCR) measurement of
hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded.
EXCEPTION: Participants with serologic findings suggestive of HBV vaccination
(anti-HBs positivity as the only serologic marker) AND a known history of prior HBV
vaccination, do not need to be tested for HBV DNA by PCR; (c) Seropositive for
hepatitis C (anti-hepatitis C virus [HCV] antibody positive or HCV-RNA quantitation
positive), except in the setting of a sustained virologic response, defined as
aviremia at least 12 weeks after completion of antiviral therapy)
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 that has spread from
where it first started (primary site) 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] PET/CT, CT or 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)
• Age >= 18 years
• 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 CT or 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
Regional Radiotherapy in Biomarker Low-Risk Node Positive and T3N0 Breast Cancer (TAILOR RT)
The purpose of this study is to compare the effects on low risk breast cancer receiving usual
care that includes regional radiation therapy, with receiving no regional radiation therapy.
Researchers want to see if not giving this type of radiation treatment works as well at
preventing breast cancer from coming back.
• Patients must be women with newly diagnosed histologically proven invasive carcinoma
of the breast with no evidence of metastases, staged as per site standard of care.
• Patients must have been treated by BCS or mastectomy with clear margins of excision.
Post-mastectomy positive margins for invasive disease and/or DCIS is not allowed.
Multifocal disease (i.e. the presence of two or more foci or breast cancer within the
same breast quadrant) and multicentric disease (i.e. the presence of two or more foci
of breast cancer in different quadrants of the same breast) are allowed.
• Patients with T3N0 disease are eligible.
• Patients with disease limited to nodal micrometastases are eligible
• Patients with nodal macrometastases (>2mm) treated by axillary dissection must have
1-3 positive axillary nodes (macrometastases, > 2 mm).
• Patients treated by mastectomy and SLNB alone must have only 1-2 positive axillary
nodes (macrometastases, > 2 mm).
• Patients must be ER ≥ 1% and HER2 negative on local testing
• Patients must have an Oncotype DX recurrence score ≤25 obtained from testing of breast
tumour tissue from a core biopsy or from the surgical specimen.
• Patient must consent to provision of, and investigator(s) must agree to submit to the
CCTG Central Tumour Bank, a representative formalin fixed paraffin block of tumour
tissue in order that the specific correlative marker assays described in the protocol
may be conducted
• Patient must consent to provision of samples of blood in order that the specific
correlative marker assays described in the protocol may be conducted.
• Patients must have had endocrine therapy initiated or planned for ≥ 5 years.
Premenopausal women will receive ovarian ablation plus aromatase inhibitor therapy or
tamoxifen if adjuvant chemotherapy was not administered. For all patients, endocrine
therapy can be given concurrently or following RT.
• Patients may or may not have had adjuvant chemotherapy.
• RT must commence within 16 weeks of definitive surgery if the patient is not treated
with chemotherapy. If adjuvant chemotherapy is given, RT must begin within 12 weeks
after the last dose. (Note: adjuvant chemotherapy may be ongoing at the time of
randomization). Definitive surgery is defined as the last breast cancer-related
surgery.
• Patient's ECOG performance status must be 0, 1 or 2.
• Patient's age must be ≥ 35 years.
• For the first 736 eligible English or French-speaking subjects who have agreed to
optional questionnaire completion: Patient is able (i.e. sufficiently fluent) and
willing to complete the quality of life, health utilities and lost productivity
questionnaires in either English or French (note: enrollment completed 2022Aug02)
• Patient consent must be appropriately obtained in accordance with applicable local and
regulatory requirements
• Patients must be accessible for treatment and follow-up. Investigators must assure
themselves the patients randomized on this trial will be available for complete
documentation of the treatment, adverse events, and follow-up.
• In accordance with CCTG policy, protocol treatment is to begin within 6 weeks of
patient randomization.
• Women of childbearing potential must have agreed to use an effective contraceptive
method. A woman is considered to be of "childbearing potential" if she has had menses
at any time in the preceding 12 consecutive months.
Exclusion Criteria:
• Patients with nodal disease limited to isolated tumour cells (pN0i+ < 0.2 mm).
• Patients with pT3N1 and pT4 disease (Note: patients with T3N0 are eligible).
• Any prior history, not including the index cancer, of ipsilateral invasive breast
cancer or ipsilateral DCIS treated with radiation therapy. (Patients with synchronous
or previous ipsilateral LCIS are eligible.)
• Synchronous or previous contralateral invasive breast cancer. (Patients with
contralateral DCIS are eligible unless previously treated with radiation.)
• History of non-breast malignancies except adequately treated non-melanoma skin
cancers, in situ cancers treated by local excision or other cancers curatively treated
with no evidence of disease for ≥ 5 years.
• Patients who are pregnant.
• Patients that have had prior ipsilateral chestwall/thoracic radiation.
• Patients treated with chemo or endocrine therapy administered in the neoadjuvant
setting for breast cancer. Endocrine therapy exposure 12 weeks or less prior to
surgery is permitted.
• Patients with serious non-malignant disease (e.g. cardiovascular, scleroderma etc.)
which would preclude RT.
• Patients with any serious active or co-morbid medical conditions, laboratory
abnormality, psychiatric illness, active or uncontrolled infections, or serious
illnesses or medical conditions that would prevent the patient from participating or
to be managed according to the protocol (according to investigator's decision).
Radiation: Radiation, Other: No Radiation
Breast Cancer, Breast - Female
UT Southwestern; Parkland Health & Hospital System
89Zr-DFO-Atezolizumab ImmunoPET/CT in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma
This is an exploratory clinical trial to assess the potential of 89Zr-DFO-Atezolizumab
Positron Emission Tomography/Computed Tomography (PET/CT) scans in patients with locally
advanced or metastatic renal cell carcinoma (RCC). This open label, nontherapeutic trial will
test the correlation of 89Zr-DFO-Atezolizumab immunoPET/CT with programmed death-ligand 1
(PD-L1) expression and the response to immune checkpoint inhibitor therapy in patients with
RCC. There will be two cohorts, one made up of patients with localized RCC who will undergo
89Zr-DFO-Atezolizumab PET/CT prior to nephrectomy and a second cohort of patients with
metastatic RCC who will undergo 89Zr-DFO-Atezolizumab PET/CT prior to treatment with an
immune checkpoint inhibitor.
• Patients with suspected renal cell carcinoma with planned surgery or patients with
metastatic RCC and a tissue diagnosis. (In standard clinical practice, biopsy is not
routinely performed in patients who will be having surgery).
• Ability to understand and the willingness to sign a written informed consent.
• Patient must be able to lie still for a 30 to 60 minute PET/CT scan.
• One of the following:
1. Patients with locally advanced RCC planned for surgery determined to be a high
risk of recurrence, defined by presence of at least clinical T2 or thioredoxin 1
(TxN1), OR patients with metastatic RCC for whom treatment with metastasectomy is
planned by the treating physician.
2. Patients with metastatic RCC for whom immuno-oncology (IO) therapy is planned.
• Women of child-bearing potential must agree to undergo and have documented a negative
pregnancy test on the day of 89Zr-DFO-Atezolizumab administration. A female of
child-bearing potential is any woman (regardless of sexual orientation, having
undergone a tubal ligation, or remaining celibate by choice) who meets the following
criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e.,
has had menses at any time in the preceding 12 consecutive months).
Exclusion Criteria:
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to
atezolizumab or any other chimeric or humanized antibodies.
• Uncontrolled severe and irreversible intercurrent illness or psychiatric
illness/social situations that would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital
abnormalities and the potential of this regimen to harm nursing infants.
• Significant autoimmune disease requiring treatment with either prednisone (or steroid
equivalent) at a dose > 10 mg/day or other immunosuppressive agents. (Replacement
steroid therapy is acceptable).
• Any patient for whom ICI therapy would be contraindicated for other reasons. Patients
with adverse reactions to ICI therapy may undergo second 89Zr-DFO-Atezolizumab
injection and PET/CT at the discretion of the treating physician considering that the
dose of antibody represents 1% of a single therapeutic dose and therefore unlikely to
cause adverse events.
• Subjects unable to provide informed consent.
• Subjects who are claustrophobic or have other contraindications to PET/CT.
• Subjects must not weigh more than the maximum weight limit for the table for the
PET/CT scanner where the study is being performed. (>200 kg or 440 lbs).
Trial of DFP-10917 vs Non-Intensive or Intensive Reinduction for AML Patients in 2nd/3rd/4th Salvage
Phase III, multicenter, randomized study with two arms (1:1 ratio) enrolling patients with
AML relapsed/refractory after 2, 3, or 4 prior induction regimens:
Experimental arm: DFP-10917 14-day continuous intravenous (IV) infusion at a dose of 6
mg/m²/day followed by a 14-day resting period per 28-day cycles.
Control arm: Non-Intensive Reinduction (LoDAC, Azacitidine, Decitabine, Venetoclax
Combination Regimens) or Intensive Reinduction (High and Intermediate Dose Cytarabine
Regimens), depending on the patient's prior induction treatment.
1. Histologically or pathologically confirmed diagnosis of AML based on WHO
classification that has relapsed after, or is refractory to, two, three, or four prior
induction regimens that may have included intensive chemotherapy (e.g., "7+3"
cytarabine and daunorubicin), epigenetic therapy (i.e., azacitidine or decitabine), or
targeted therapy (e.g., FLT-3, IDH-1/2, BCL-2, monoclonal antibody).
(Relapse is defined as reemergence of ≥5% leukemia blasts in bone marrow or ≥1% blasts
in peripheral blood ≥90 days after first CR or CR without complete platelet recovery
(CRp). Refractory AML is defined as persistent disease ≥28 days after initiation of
intensive induction therapy (up to two induction cycles) or relapse <90 days after
first CR or CRp. Refractory disease for patients undergoing hypomethylating agent
induction is defined as lack of remission following at least 2 cycles of epigenetic
therapy without reduction in bone marrow blast status.)
Patients with a history of IPSS-R high or very high risk MDS that transformed to AML
during treatment with hypomethylating drugs and then relapse following or are
refractory to a subsequent AML induction regimen may be enrolled as Second Salvage AML
patients. Additionally, patients with a history of MPN in accelerated phase (MPN-AP)
or high-risk primary myelofibrosis (PMF) that transformed to AML during treatment with
hypomethylating drugs and then relapse following or are refractory to a subsequent AML
induction regimen may be enrolled as Second Salvage AML patients.
2. Aged ≥ 18 years.
3. ECOG Performance Status of 0, 1 or 2.
4. Adequate clinical laboratory values (i.e., plasma creatinine <2.5 x upper limit of
normal (ULN) for the institution, bilirubin <2.5 x ULN, alanine transaminase (ALT) and
aspartate transaminase (AST) ≤2.5 x ULN).
5. Absence of active central nervous system (CNS) involvement by leukemia. Patients with
previously diagnosed CNS leukemia are eligible if the CNS leukemia is under control
and intrathecal treatment may continue throughout the study.
6. Absence of uncontrolled intercurrent illnesses, including uncontrolled infections,
cardiac conditions, or other organ dysfunctions.
7. Signed informed consent prior to the start of any study specific procedures.
8. Women of child-bearing potential must have a negative serum or urine pregnancy test.
9. Male and female patients must agree to use acceptable contraceptive methods for the
duration of the study and for at least one month after the last drug administration.
Exclusion Criteria:
1. The interval from prior treatment to time of study drug administration is < 2 weeks
for cytotoxic agents or < 5 half-lives for noncytotoxic agents. Exceptions: Use of
hydroxyurea is allowed before the start of study and is to be discontinued prior to
the initiation of study treatment. At the investigator's discretion, for patients with
significant leukocytosis that develops during the early treatment cycles, hydroxyurea
may be administered. The hydroxyurea should be discontinued as soon as clinically
appropriate.
2. Any >grade 1 persistent clinically significant toxicities from prior chemotherapy.
3. Inadequate Cardiac (left ventricular ejection fraction ≤40%) function.
4. White blood cell (WBC) count >15,000/μL (Note: Patients considered for possible
venetoclax-containing regimen must have WBC ≤10k/μL prior to initiating venetoclax
treatment).
5. For patients with prior hematopoietic stem cell transplant (HSCT):
1. Less than 3 months since HSCT
2. Acute Graft versus Host Disease (GvHD) >Grade 1
3. Chronic GvHD >Grade 1
6. Any concomitant condition that in the opinion of the investigator could compromise the
objectives of this study and the patient's compliance.
7. A pregnant or lactating woman.
8. Current malignancies of another type. Exceptions: Patients may participate if they
have previously treated and currently controlled prostate cancer, or adequately
treated in situ cervical cancer or basal cell skin cancer, or other malignancies with
no evidence of disease for 2 years or more.
9. Patient has acute promyelocytic leukemia (APL).
10. Patients with known HIV, active HBV or active HCV infection (note: testing for these
infections is not required). For patients with evidence of chronic hepatitis B virus
(HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if
indicated. Patients with a history of hepatitis C virus (HCV) infection must have been
treated and cured. For patients with HCV infection who are currently on treatment,
they are eligible if they have an undetectable HCV viral load.
11. Documented or known clinically significant bleeding disorder.
A Study of CC-99712, a BCMA Antibody-Drug Conjugate, in Participants With Relapsed and Refractory Multiple Myeloma
Study CC-99712-MM-001 is an open-label, Phase 1, dose escalation (Part A) and expansion (Part
B), First-in-Human (FIH) clinical study of CC-99712 in monotherapy or combination with
BMS-986405 in participants with relapsed and refractory multiple myeloma (MM). The dose
escalation part (Part A) of the study will evaluate the safety and tolerability of escalating
doses of CC-99712, administered intravenously (IV) in monotherapy (Arm 1) or combination with
BMS-986405 (Arm 2), to determine the maximum tolerated dose (MTD) of CC-99712 guided by a
Bayesian logistic regression model (BLRM). A modified accelerated titration design will also
be used for Arm 1 and Arm 2. The MTD may be established separately for CC-99712 administered
at Q3W and/ or Q4W schedules. The expansion part (Part B) will further evaluate the safety
and efficacy of CC-99712 in monotherapy (Arm 1) or combination (Arm 2) administered at or
below the MTD in selected expansion cohorts in order to determine the RP2D. One or more doses
or dosing regimens may be selected for cohort expansion. All participants will be treated
until confirmed disease progression per IMWG criteria, unacceptable toxicity, or
participants//Investigator decision to withdraw.
Participants must satisfy the following criteria to be enrolled in the study:
Inclusion
• Participant is ≥ 18 years of age at the time of signing the ICF.
• Participant has a history of multiple myeloma (MM) with relapsed and/or refractory
disease
• Participant must have measurable disease.
• Participant has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of
0 or 1.
Exclusion Criteria
• Participant has symptomatic central nervous system involvement of MM.
• Participant had a prior autologous stem cell transplant ≤ 3 months prior to starting
CC-99712.
• Participant had a prior allogeneic stem cell transplant with either standard or
reduced intensity conditioning ≤ 6 months prior to starting CC-99712 or is on systemic
immunosuppression for graft-versus host disease.
• Subject is a pregnant or lactating female.
• Subject has known human immunodeficiency virus (HIV) infection.
• Subject has active hepatitis B or C (HBV/HCV) infection.
Other protocol-defined inclusion/exclusion criteria apply
Drug: CC-99712, Drug: BMS-986405
Multiple Myeloma
Multiple Myeloma, Relapsed and refractory, CC-99712, BCMA, Antibody drug conjugate, BMS-986405
A Study of Erdafitinib Versus Investigator Choice of Intravesical Chemotherapy in Participants Who Received Bacillus Calmette-Guérin (BCG) and Recurred With High Risk Non-Muscle-Invasive Bladder Cancer (NMIBC)
The purpose of this study is to evaluate recurrence-free survival (RFS) in participants
treated with erdafitinib vs Investigator's Choice, for participants with high-risk
non-muscle-invasive bladder cancer (NMIBC) who harbor fibroblast growth factor receptor
(FGFR) mutations or fusions, and who recurred after bacillus calmette-guerin (BCG) therapy.
• Histologically confirmed, recurrent, non-muscle-invasive urothelial carcinoma of the
bladder. Variant pathology are allowed
• Tumor with specified fibroblast growth factor receptor (FGFR) mutations or fusions
• Bacillus Calmette- Guerin (BCG)-unresponsive after adequate BCG therapy or BCG
experienced participants
• Refuses or is not eligible for cystectomy (Cohort 1 and Cohort 2 only)
• Eastern Cooperative Oncology Group (ECOG) performance status Grade 0-1
• Must sign an informed consent form (ICF) (or their legally acceptable representative
must sign) indicating that he or she understands the purpose of, and procedures
required for, the study and is willing to participate in the study
• A woman of childbearing potential must have a negative pregnancy test (beta-hCG
[beta-human chorionic gonadotropin]) (urine or serum) within 7 days before
randomization (Cohort 1) or the first dose of study drug (Cohort 2 and Cohort 3)
• Adequate bone marrow, liver, and renal function as specified in the protocol
Exclusion Criteria:
• Histologically confirmed, muscle-invasive (T2 or higher stage) urothelial carcinoma of
the bladder
• Histopathology demonstrating any small cell component, pure adenocarcinoma, pure
squamous cell carcinoma, or pure squamous CIS of the bladder
• Prior treatment with an FGFR inhibitor
• Active malignancies other than the disease being treated under study. The only allowed
exceptions are: (a) skin cancer treated within the last 24 months that is considered
completely cured (b) adequately treated lobular carcinoma in situ (LCIS) and ductal
CIS (c) history of localized breast cancer and receiving antihormonal agents, or
history of localized prostate cancer (N0M0) and receiving androgen deprivation therapy
• Current central serous retinopathy or retinal pigment epithelial detachment of any
grade
CAMPFIRE: A Study of Ramucirumab (LY3009806) in Children and Young Adults With Desmoplastic Small Round Cell Tumor
This study is being conducted to test the safety and efficacy of ramucirumab in combination
with other chemotherapy in the treatment of relapsed, recurrent, or refractory desmoplastic
small round cell tumor (DSRCT) in children and young adults. This trial is part of the
CAMPFIRE master protocol which is a platform to accelerate the development of new treatments
for pediatric and young adult participants with cancer. Your participation in this trial
could last 12 months or longer, depending on how you and your tumor respond.
• Participants must have discontinued all previous treatments for cancer or
investigational agents ≥7 days after the last dose or per the type of previous
treatment as stated in the protocol and must have recovered from the acute effects to
≤Grade 2 for alopecia and decreased tendon reflex and to ≤Grade 1 for all other
effects at the time of enrollment, unless otherwise noted. Consult with the Lilly
clinical research physician or scientist for the appropriate length of time prior to
the first dose of study treatment.
• Participants with relapsed, recurrent, or refractory DSRCT.
• Participants must:
• Have measurable disease by Response Evaluation Criteria in Solid Tumors, Version
(RECIST) 1.1.
• Have received at least one prior line of systemic treatment (including
neoadjuvant and adjuvant chemotherapy). This prior treatment must include
approved therapies for which they are eligible, unless the participant is not a
suitable candidate for the approved therapy.
• Not be eligible for surgical resection at time of enrollment.
• Adequate cardiac function, defined as: Shortening fraction of ≥27% by echocardiogram,
or ejection fraction of ≥50% by gated radionuclide study.
• Adequate blood pressure (BP) control, defined as:
• Participants ≥18 years: Controlled hypertension defined as systolic BP ≤150
millimeters of mercury (mmHg) or diastolic BP ≤90 mmHg where standard medical
management is permitted. Please note that ≥2 serial BP readings should be
obtained and averaged to determine baseline BP.
• Participants <18 years: A BP ≤95th percentile for age, height, and gender
measured as described in National High Blood Pressure Education Program Working
Group (NHBPEPWG) on High Blood Pressure in Children and Adolescents (2004), where
standard medical management is permitted. Please note that ≥2 serial BP readings
should be obtained and averaged to determine baseline BP.
• Adequate hematologic function, as defined as:
• Absolute neutrophil count (ANC): ≥750/microliters (µL) granulocyte-colony
stimulating factor (G-CSF) permitted up to 48 hours prior. Participants with
documented history of benign ethnic neutropenia or other conditions could be
considered with a lower ANC after discussion with and approval from the Lilly
clinical research physician or scientist.
• Platelets: ≥75,000/cubic millimeters. Platelet transfusion permitted up to 72
hours prior.
• Hemoglobin: ≥8 grams per deciliter (g/dL) (≥80 g/liter). Transfusions to increase
the participant's hemoglobin level to at least 8 g/dL are permitted; however,
study treatment must not begin until 7 days after the transfusion, and complete
blood count criteria for eligibility are confirmed within 24 hr of first study
dose.
• Adequate renal function, as defined as:
• Creatinine clearance or radioscope glomerular filtration rate (GFR) ≥60
milliliters/minute/meters squared OR serum creatinine meeting the following
parameters:
• for participants ≥18 years of age serum creatinine ≤1.5×upper limit of
normal (ULN);
• for participants <18 years of age, serum creatinine based on age/gender as
follows: Age 1 to <2 years maximum serum creatinine 0.6, Age 2 to <6 years
maximum serum creatinine 0.8, Age 6 to <10 years maximum serum creatinine
1.0, Age 10 to <13 years maximum serum creatinine 1.2, Age 13 to <16 years
maximum serum creatinine 1.5 for males and 1.4 for females, Age 16 to <18
years maximum serum creatinine 1.7 for males and 1.4 for females.
• Urine protein meeting the following parameters:
• for participants ≥18 years of age: <2+ on dipstick or routine urinalysis. If
urine dipstick or routine analysis indicates proteinuria ≥2+, then a 24-hour
urine must be collected and must demonstrate <2 grams of protein in 24 hours
to allow participation in the study.
• for participants <18 years of age: ≤30 milligrams per deciliter urine
analysis or <2+ on dipstick. If urine dipstick or routine analysis indicates
proteinuria ≥2+, then a 24-hour urine must be collected and must demonstrate
<1 g of protein in 24 hours to allow participation in the study.
• Adequate liver function:
• Total bilirubin: ≤1.5×ULN. Except participants with document history of Gilbert
Syndrome who must have a total bilirubin level of <3.0×ULN.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): ≤2.5×ULN OR
≤5.0×ULN if the liver has tumor involvement.
• The participant has an adequate coagulation function as defined by International
Normalized Ratio ≤1.5 or prothrombin time ≤1.5×ULN, and partial thromboplastin time
≤1.5×ULN if not receiving anticoagulation therapy. For participants receiving
anticoagulants, exceptions to these coagulation parameters are allowed if they are
within the intended or expected range for their therapeutic use. Participants must
have no history of clinically significant active bleeding (defined as within 14 days
of first dose of study drug) or pathological condition that carries a high risk of
bleeding (for example, tumor involving major vessels or known esophageal varices).
• The participant has adequate hematologic and organ function ≤1 week (7 days) prior to
first dose of study drug.
• Female participants of childbearing potential must have a negative urine or serum
pregnancy test within 7 days prior to randomization. Male and female participants must
agree to use highly effective contraception for the duration of the study and up to 3
months following the last dose of ramucirumab and vinorelbine, and 12 months following
the last dose of cyclophosphamide in order to prevent pregnancy.
Exclusion Criteria:
• Participants with severe and/or uncontrolled concurrent medical disease or psychiatric
illness/social situation that in the opinion of the investigator could cause
unacceptable safety risks or compromise compliance with the protocol.
• Participants who have active infections requiring therapy.
• Participants with an active fungal, bacterial, and/or known severe viral
infection including, but not limited to, human immunodeficiency virus (HIV) or
viral (A, B, or C) hepatitis (screening is not required).
• Participants who have had allogeneic bone marrow or solid organ transplant are
excluded.
• Surgery: Participants who have had, or are planning to have, the following invasive
procedures are not eligible:
• Major surgical procedure, laparoscopic procedure, or significant traumatic injury
within 28 days prior to enrollment.
• Central line placement or subcutaneous port placement is not considered major
surgery.
• Core biopsy, fine needle aspirate, and bone marrow biopsy/aspirate are not
considered major surgeries.
• Surgical or other wounds must be adequately healed prior to enrollment.
• Bleeding and thrombosis:
• Participants with evidence of active bleeding or a history of significant (≥Grade
3) bleeding event within 3 months prior to enrollment are not eligible.
• Participants with a bleeding diathesis or vasculitis are not eligible.
• Participants with known or prior history in the prior 3 months of esophageal
varices are not eligible.
• Participants with a history of deep vein thrombosis requiring medical
intervention (including pulmonary embolism) within 3 months prior to study
enrollment are not eligible.
• Participants with a history of hemoptysis or other signs of pulmonary hemorrhage
within 3 months prior to study enrollment are not eligible.
• Cardiac:
• Participants with a history of central nervous system (CNS) arterial/venous
thromboembolic events (VTEs) including transient ischemic attack (TIA) or
cerebrovascular accident (CVA) within 6 months prior to study enrollment are not
eligible.
• Participants with myocardial infarction or unstable angina within the prior 6
months.
• Participants with New York Heart Association Grade 2 or greater congestive heart
failure (CHF).
• Participants with serious and inadequately controlled cardiac arrhythmia.
• Participants with significant vascular disease (eg, aortic aneurysm, history of
aortic dissection).
• Participants with clinically significant peripheral vascular disease.
• Participants who have a history of fistula, gastrointestinal (GI) ulcer or
perforation, or intra-abdominal abscess within 3 months of study enrollment are not
eligible.
• Participants with a history of hypertensive crisis or hypertensive encephalopathy
within 6 months of study enrollment are not eligible.
• Participants who have non-healing wound, unhealed or incompletely healed fracture, or
a compound (open) bone fracture at the time of enrollment are not eligible.
• Participants previously treated and progressed on combination cyclophosphamide and
vinorelbine regimen. Participants who received combination as maintenance therapy,
without progression, would be eligible.
• Participants with a known hypersensitivity to ramucirumab, cyclophosphamide,
vinorelbine or any of the excipients of the medicinal products.
• Hepatic impairment:
• Severe liver cirrhosis Child-Pugh Class B (or worse).
• Cirrhosis with a history of hepatic encephalopathy.
• Clinically meaningful ascites resulting from cirrhosis and requiring ongoing
treatment with diuretics and/or paracentesis.
• History of hepatorenal syndrome.
• The participant has a bowel obstruction, history or presence of inflammatory
enteropathy or extensive intestinal resection (eg, hemicolectomy or extensive small
intestine resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or
chronic diarrhea.
• The participant has a urinary outflow obstruction.
• The participant has Grade 2 hematuria or non-infectious cystitis at the time of
screening.
• Participants with central nervous system (CNS) involvement are ineligible.
Gemcitabine and Cisplatin Without Cystectomy for Patients With Muscle Invasive Bladder Urothelial Cancer and Select Genetic Alterations
This phase II trial studies how well gemcitabine hydrochloride and cisplatin work in treating
participants with invasive bladder urothelial cancer. Drugs used in chemotherapy, such as
gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor
cells, either by killing the cells, by stopping them from dividing, or by stopping them from
spreading.
• Step 1 Patient Registration Eligibility Criteria
• Histologically confirmed muscle-invasive urothelial carcinoma of the bladder.
Urothelial carcinoma invading into the prostatic stroma with no histologic muscle
invasion is allowed, provided the extent of disease is confirmed via imaging and/or
examination under anesthesia (EUA). The diagnostic TURBT sample must have been
obtained within 60 days prior to registration
• 20 unstained slides (10 micron thickness) of formalin-fixed paraffin-embedded (FFPE)
pre-treatment diagnostic transurethral resection (TUR) specimen available (for
sequencing), with 2 (5 micron) slides at the start and end of the 20 slides, for a
total of 22 unstained slides. An FFPE block is also acceptable
• Clinical stage T2-T4aN0/xM0 disease
• Medically appropriate candidate for radical cystectomy as assessed by surgeon
• No concomitant multifocal carcinoma in situ; a single focus is allowed
• A single muscle-invasive bladder tumor measuring ≤5 cm in size as defined by the
surgeons at cystoscopic evaluation. When documented, pathologic size at cystoscopy and
TURBT will take precedence over radiographic measurements of tumor size.
• No clinical or radiographic evidence for locally advanced or metastatic disease
• No prior anti-PD-1 or anti PD-L1 therapies, or systemic chemotherapy within the past 5
years (prior intravesical induction immunotherapy for non-muscle invasive disease is
allowed, defined as BCG x6 doses and maintenance therapy); BCG refractory disease,
defined as disease recurrence within 3 months of BCG therapy, is not allowed.
Intravesical chemotherapy is allowed.
• No prior radiation therapy to the bladder or prostate
• No major surgery or radiation therapy =< 4 weeks of registration (TURBT is allowed).
• Not pregnant and not nursing. This study involves an agent that has known genotoxic,
mutagenic and teratogenic effects. For women of childbearing potential only, a
negative pregnancy test done =< 14 days prior to registration is required
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Absolute neutrophil count (ANC) >= 1,000/mm^3
• Platelet count >= 100,000/mm^3
• Calculated creatinine clearance ≥ 55 mL/min using formula per institutional standard
or investigator's discretion. The same formula should be used to calculate all
subsequent creatinine clearances.
• Total bilirubin =< 1.5 x upper limit of normal (ULN)
* (For patients with documented Gilbert's syndrome Total Bilirubin =< 3 x ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
• Alkaline phosphatase =< 2.5 x ULN
• No evidence of New York Heart Association (NYHA) functional class III or IV heart
disease
• No ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Terminology
Criteria for Adverse Events (CTCAE) version 5.0 grade >= 2
• No pre-existing sensory grade >= 2 neuropathy
• No pre-existing grade >= 2 hearing loss
• No serious intercurrent medical or psychiatric illness, including serious active
infection
• None of the following within the 6 months prior to study drug administration:
myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
graft, symptomatic congestive heart failure, cerebrovascular accident, or transient
ischemic attack
• No known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
(AIDS)-related illness or other active infection. HIV-positive patients on combination
antiretroviral therapy are ineligible because of the potential for pharmacokinetic
interactions with the drugs used in this trial. In addition, these patients are at
increased risk of lethal infections when treated with marrow-suppressive therapy.
Appropriate studies will be undertaken in patients receiving combination
antiretroviral therapy, when indicated
• No history of allergic reaction attributed to compounds of similar chemical or
biologic composition to the agents used in this study
• No concurrent treatment on another clinical trial; supportive care trials or
non-therapeutic trials (e.g., quality of life) are allowed
• No prior malignancy except for: adequately treated basal or squamous cell skin cancer,
in situ cervical cancer, adequately treated stage I or II cancer from which the
patient is currently in complete remission, or any other cancer from which the patient
has been disease free for five years. Patients with localized prostate cancer who are
being followed by an active surveillance program are also eligible
• Step 2 Patient Registration Eligibility Criteria
• Patients must have completed 4 or more cycles of protocol-directed chemotherapy and
DDR gene results must be available
• Step 3 Patient Registration Eligibility Criteria (only patients with a DDR gene
alteration)
• Deleterious alteration within 1 or more of 9 pre-defined DDR genes within the
pre-treatment TURBT deoxyribonucleic acid (DNA)
• Cystoscopy and imaging performed to determine stage/treatment assignment
HYPORT: A Phase I/II Study of Hypofractionated Post-operative Radiation Therapy for Head and Neck Cancer
There is a strong radiobiological and economic rationale for hypofractionated radiation
therapy in head and neck cancer. Phase 1 of the trial aims to assess the acute toxicity and
tolerability of hypofractionated radiation therapy in the post-operative setting, and to
determine the dose/fractionation for Phase 2. Phase 2 aims to establish non-inferiority of
swallowing-related quality of life and to assess the toxicity and efficacy of
hypofractionated radiation therapy compared to conventionally fractionated radiation therapy
in the post-operative setting.
Inclusion criteria will be the same for Phase I and Phase II.
1. Pathologically proven diagnosis of stage I-IVB squamous cell carcinoma of the oral
cavity, oropharynx, hypopharynx, or larynx status post gross total resection with
pathology showing one or more of the following intermediate risk factors:
• T3/4 disease (AJCC 8th edition), positive lymph node(s), close margin(s),
perineural invasion, and/or lymphovascular invasion
• Close margin(s) defined as either:
• Final patient margin of <5 mm without disease on ink OR
• Initial positive margin in the specimen regardless of the final patient
margin (e.g. if resection margin on the initial specimen is positive, final
patient margin after subsequent resections can be ≥5 mm and still be
considered close margin)
2. Age ≥18 years
3. ECOG performance status 0-2
4. Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for 90 days following completion of therapy.
Medically acceptable birth control (contraceptives) includes:
• approved hormonal contraceptives (such as birth control pills, patch or ring;
Depo-Provera, Implanon), or
• barrier methods (such as condom or diaphragm) used with a spermicide
Should a woman become pregnant or suspect she is pregnant while participating in this
study, she should inform her treating physician immediately.
A female of child-bearing potential is any woman (regardless of sexual orientation,
having undergone a tubal ligation, or remaining celibate by choice) who meets the
following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e.,
has had menses at any time in the preceding 12 consecutive months).
5. Negative serum or urine pregnancy test within 2 weeks before registration for women of
childbearing potential.
6. Ability to understand and the willingness to sign a written informed consent
Exclusion Criteria:
Phase I:
1. Distant metastasis
2. Stage I and II glottic squamous cell carcinoma
3. High risk factors following surgical resection requiring concurrent chemotherapy:
final positive margin(s) and/or extranodal extension
4. Feeding tube dependence at baseline assessment.
5. Synchronous non-skin cancer primaries outside of the oropharynx, oral cavity, larynx,
and hypopharynx except for low- and intermediate-risk prostate cancer and synchronous
well-differentiated thyroid cancer. For prostate cancer, patient should not be
receiving active treatment. For thyroid cancer, thyroid surgery may occur before or
after treatment, provided all other eligibility criteria are met.
6. Prior invasive malignancy with an expected disease-free interval of less than 3 years
7. Prior radiotherapy to the region of the study cancer that would result in overlap of
radiation fields
8. Subjects may not be receiving any other investigational agents for the treatment of
the cancer under study.
9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that, in the opinion of the
investigator, would limit compliance with study requirements
10. Subjects must not be pregnant or nursing due to the potential for congenital
abnormalities and the potential of this regimen to harm nursing infants.
11. History of severe immunosuppression, including HIV, and organ or autologous or
allogeneic stem cell transplant
Phase II:
The exclusion criteria will be the same as Phase I except for feeding tube dependence.
Patients who are feeding tube dependent are excluded from Phase I to accurately assess
treatment associated toxicity affecting swallowing and oral intake. During Phase II,
patients who are feeding tube dependent will be eligible to enroll and stratified at
randomization.
Standard Systemic Therapy With or Without Definitive Treatment in Treating Participants With Metastatic Prostate Cancer
This phase III trial studies how well standard systemic therapy with or without definitive
treatment (prostate removal surgery or radiation therapy) works in treating participants with
prostate cancer that has spread to other places in the body. Addition of prostate removal
surgery or radiation therapy to standard systemic therapy for prostate cancer may lower the
chance of the cancer growing or spreading.
• STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: All patients must have a histologically
or cytologically proven diagnosis of adenocarcinoma of the prostate. Patients with
pure small cell carcinoma* (SCC), sarcomatoid, or squamous cell carcinoma are not
eligible. (*morphology must be consistent with SCC; synaptophysin or chromogranin
positive by immunohistochemical staining is insufficient to diagnose SCC).
• STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: Patients must have an intact prostate.
No prior local therapy for prostate adenocarcinoma is allowed (e.g., brachytherapy,
high-intensity focused ultrasound [HIFU], cryotherapy, laser ablative therapies). Any
prior therapy for benign conditions, such as obstruction, are acceptable (e.g.,
transurethral resection of the prostate, greenlight laser ablation, microwave
ablation).
• STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: Patients must have evidence of
metastatic disease on technetium bone scan and computed tomography (CT) or magnetic
resonance imaging (MRI) within 42 days prior to starting standard systemic therapy.
Metastatic disease that is detected by positron emission tomography (PET) scan only
(sodium fluoride [NaF], prostate-specific membrane antigen [PSMA],
anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid [FACBC], carbon [C]11) but not
conventional imaging (technetium [Tc]99 bone scan, CT or MRI) or solitary metastases
by conventional imaging, must be confirmed histologically or cytologically.
• STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: Patients with known brain metastases
are not eligible. Brain imaging studies are not required for eligibility if the
patient has no neurologic signs or symptoms suggestive of brain metastasis. If brain
imaging studies are performed, they must be negative for disease.
• STEP 1 REGISTRATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must have received no
more than 28 weeks of standard systemic therapy (SST). SST is defined as current
National Comprehensive Cancer Network (NCCN) guidelines for metastatic prostate
cancer.
• STEP 1 REGISTRATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must not have
progressed while on SST.
• STEP 1 REGISTRATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients with oligometastatic
prostate cancer may receive metastasis directed therapy to up to four sites of disease
prior to randomization.
• STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: Patients must have a complete
physical examination and medical history within 28 days prior to registration.
• STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: Patients must have a PSA documented
prior to initiation of SST and within 28 days prior to registration. Any additional
PSAs measured while receiving SST should be recorded.
• STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: Patients must have a testosterone
lab documented within 28 days prior to randomization. Any additional testosterone labs
measured while receiving SST should be recorded as well as pretreatment initiation if
available.
• STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: No other prior malignancy is
allowed except for the following: adequately treated basal cell or squamous cell skin
cancer, adequately treated stage 0, I or II cancer from which the patient is currently
in complete remission, or any other cancer from which the patient has been disease
free for three years.
• STEP 1 REGISTRATION: SPECIMEN SUBMISSION CRITERIA: Patients must be offered the
opportunity to participate in translational medicine studies and specimen banking for
future studies.
• STEP 1 REGISTRATION: QUALITY OF LIFE CRITERIA: Patients who can complete
Patient-Reported Outcome instruments in English, Spanish or French, must participate
in the quality of life studies.
• STEP 1 REGISTRATION: REGULATORY CRITERIA: Patients must be informed of the
investigational nature of this study and must sign and give written informed consent
in accordance with institutional and federal guidelines.
• STEP 2 RANDOMIZATION: DISEASE-RELATED CRITERIA: As a part of the OPEN registration
process the treating institution's identity is provided in order to ensure that the
current (within 365 days) date of institutional review board approval for this study
has been entered in the system.
• STEP 2 RANDOMIZATION: DISEASE-RELATED CRITERIA: Patients must have no evidence of
disease progression during the 28 weeks of SST by PSA measure, bone scan and CT or MRI
or symptomatic deterioration (as defined by physician discretion) within 28 days prior
to randomization.
• STEP 2 RANDOMIZATION: DISEASE-RELATED CRITERIA: Patients must have consultation with a
urologist and have surgically resectable disease regardless of definitive treatment
intent or randomization.
• STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must have received
between 22 and 28 weeks of SST as measured from the date of first hormonal therapy or
surgical castration. SST is defined by current NCCN guidelines for metastatic prostate
cancer.
• STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must not be planning
to receive docetaxel after randomization.
• STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Any toxicities from SST must
have resolved to =< grade 1 (Common Terminology Criteria for Adverse Events [CTCAE]
version 5.0) prior to randomization.
• STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients may have received
elective metastasis directed therapy to oligometastatic sites (=< 4 sites). All
treatment must be completed prior to randomization.
• STEP 2 RANDOMIZATION: CLINICAL/LABORATORY CRITERIA: Patients must have a PSA performed
within 28 days prior to randomization.
• STEP 2 RANDOMIZATION: CLINICAL/LABORATORY CRITERIA: Patients must have a testosterone
< 50 ng/dL within 28 days prior to randomization.
• STEP 2 RANDOMIZATION: CLINICAL/LABORATORY CRITERIA: Patients must have a Zubrod
performance status of 0 ? 1 within 28 days prior to randomization.
Efficacy and Safety of Olaparib (MK-7339) in Participants With Previously Treated, Homologous Recombination Repair Mutation (HRRm) or Homologous Recombination Deficiency (HRD) Positive Advanced Cancer (MK-7339-002 / LYNK-002)
This study will evaluate the efficacy and safety of olaparib (MK-7339) monotherapy in
participants with multiple types of advanced cancer (unresectable and/or metastatic) that: 1)
have progressed or been intolerant to standard of care therapy; and 2) are positive for
homologous recombination repair mutation (HRRm) or homologous recombination deficiency (HRD).
• Has a histologically- or cytologically-confirmed advanced (metastatic and/or
unresectable) solid tumor (except breast or ovarian cancers whose tumor has a germline
or somatic BRCA mutation) that is not eligible for curative treatment and for which
standard of care therapy has failed. Participants must have progressed on or be
intolerant to standard of care therapies that are known to provide clinical benefit.
There is no limit on the number of prior treatment regimens.
• Has either centrally-confirmed known or suspected deleterious mutations in at least 1
of the genes involved in HRR or centrally-confirmed HRD.
• For participants receiving prior platinum (cisplatin, carboplatin, or oxaliplatin
either as monotherapy or in combination) for advanced (metastatic and/or unresectable)
solid tumor, have no evidence of disease progression during the platinum chemotherapy.
• Has measurable disease per RECIST 1.1 or PCWG-modified RECIST 1.1 as assessed by the
local site Investigator/radiology and confirmed by BICR.
• Is able to provide a newly obtained core or excisional biopsy of a tumor lesion or
either an archival formalin-fixed paraffin embedded (FFPE) tumor tissue block or
slides.
• Has a life expectancy of at least 3 months.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1,
as assessed within 3 days of treatment initiation.
• Male participants must agree to use contraception during the treatment period and for
at least 90 days (3 months) after the last dose of study treatment and refrain from
donating sperm during this period.
• Female participants must not be pregnant or breastfeeding. Additionally, female
participants must either not be a woman of childbearing potential (WOCBP) or, if a
WOCBP, agree to use contraception during the treatment period and for at least 30 days
(1 month) after the last dose of study treatment.
• Has adequate organ function.
Exclusion Criteria:
• Has a known additional malignancy that is progressing or has required active treatment
in the last 5 years. Note: Participants with basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, ductal carcinoma in situ, or cervical carcinoma
in situ that has undergone potentially curative therapy are not excluded.
• Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features
suggestive of MDS/AML.
• Has known central nervous system (CNS) metastases and/or carcinomatous meningitis.
Note: Participants with previously treated brain metastases may participate if
radiologically stable, clinically stable, and without requirement for steroid
treatment for at least 14 days prior to the first dose of study treatment.
• Has received colony-stimulating factors (e.g., granulocyte colony-stimulating factor
[G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF] or recombinant
erythropoietin) within 28 days prior to the first dose of study treatment.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has known active hepatitis infection (i.e., Hepatitis B or C).
• Is unable to swallow orally administered medication or has a gastrointestinal disorder
affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).
• Has received prior therapy with olaparib or with any other polyadenosine 5'
diphosphoribose (poly[ADP ribose]) polymerization (PARP) inhibitor.
• Has a known hypersensitivity to the components or excipients in olaparib.
• Has received previous allogenic bone-marrow transplant or double umbilical cord
transplantation (dUCBT).
• Has received a whole blood transfusion in the last 120 days prior to entry to the
study. Packed red blood cells and platelet transfusions are acceptable if not
performed within 28 days of the first dose of study treatment.
Enfortumab Vedotin and Pembrolizumab vs. Chemotherapy Alone in Untreated Locally Advanced or Metastatic Urothelial Cancer (EV-302)
This study is being done to see how well two drugs (enfortumab vedotin and pembrolizumab)
work together to treat patients with urothelial cancer. The study will compare these drugs to
other drugs that are usually used to treat this cancer (standard of care). The patients in
this study will have cancer that has spread from their urinary system to other parts of their
body.
• Histologically documented, unresectable locally advanced or metastatic urothelial
carcinoma
• Measurable disease by investigator assessment according to RECIST v1.1
• Participants with prior definitive radiation therapy must have measurable disease
per RECIST v1.1 that is outside the radiation field or has demonstrated
unequivocal progression since completion of radiation therapy
• Participants must not have received prior systemic therapy for locally advanced or
metastatic urothelial carcinoma with the following exceptions:
• Participants that received neoadjuvant chemotherapy with recurrence >12 months
from completion of therapy are permitted
• Participants that received adjuvant chemotherapy following cystectomy with
recurrence >12 months from completion of therapy are permitted
• Must be considered eligible to receive cisplatin- or carboplatin-containing
chemotherapy, in the investigator's judgment
• Archival tumor tissue comprising muscle-invasive urothelial carcinoma or a biopsy of
metastatic urothelial carcinoma must be provided for PD-L1 testing prior to
randomization
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2
• Adequate hematologic and organ function
Exclusion Criteria
• Previously received enfortumab vedotin or other monomethyl auristatin E (MMAE)-based
antibody-drug conjugate (ADCs)
• Received prior treatment with a programmed cell death ligand-1 (PD-(L)-1) inhibitor
for any malignancy, including earlier stage urothelial cancer (UC), defined as a PD-1
inhibitor or PD-L1 inhibitor
• Received prior treatment with an agent directed to another stimulatory or co
inhibitory T-cell receptor
• Received anti-cancer treatment with chemotherapy, biologics, or investigational agents
not otherwise prohibited by exclusion criterion 1-3 that is not completed 4 weeks
prior to first dose of study treatment
• Uncontrolled diabetes
• Estimated life expectancy of less than 12 weeks
• Active central nervous system (CNS) metastases
• Ongoing clinically significant toxicity associated with prior treatment that has not
resolved to ≤ Grade 1 or returned to baseline
• Currently receiving systemic antimicrobial treatment for active infection (viral,
bacterial, or fungal) at the time of randomization. Routine antimicrobial prophylaxis
is permitted.
• Known active hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV)
infection.
• History of another invasive malignancy within 3 years before the first dose of study
drug, or any evidence of residual disease from a previously diagnosed malignancy
• Documented history of a cerebral vascular event (stroke or transient ischemic attack),
unstable angina, myocardial infarction, or cardiac symptoms consistent with New York
Heart Association (NYHA) Class IV within 6 months prior to randomization
• Receipt of radiotherapy within 2 weeks prior to randomization
• Received major surgery (defined as requiring general anesthesia and >24 hour inpatient
hospitalization) within 4 weeks prior to randomization
• Known severe (≥ Grade 3) hypersensitivity to any enfortumab vedotin excipient
contained in the drug formulation of enfortumab vedotin
• Active keratitis or corneal ulcerations
• History of autoimmune disease that has required systemic treatment in the past 2 years
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced
pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
chest computed tomography (CT) scan
• Prior allogeneic stem cell or solid organ transplant
• Received a live attenuated vaccine within 30 days prior to randomization
The goal of this research is to examine the ability of Gallium-68 (68Ga) Prostate-Specific
Membrane Antigen-11 (PSMA-11) positron emission tomography/computed tomography (PET/CT) to
detect sites of recurrent prostate cancer in patients with biochemical recurrence previously
treated with radical prostatectomy (RP) or external beam radiation (EBRT) and to assess
treatment response to subsequent salvage therapy.
• Patients with suspected BCR of prostate cancer following initial treatment with either
prostatectomy or definitive EBRT of the prostate or patients with known metastatic
prostate cancer who have failed systemic therapy.
• Patients being considered for salvage therapy.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0-3.
• Patients must be medically stable as judged by the patient's physician.
• Patients must be able to lie still for 20-40 minutes for the PET/CT scans.
• Ability to understand and the willingness to sign a written informed consent.
• Patients with BCR and no known lesions should not be on antiandrogen therapy at the
time of scans. Patients with known metastases who are currently being treated with
anti-androgen therapy may remain on this medication.
Exclusion Criteria:
• Patients who have or have had a biopsy proven concurrent other malignancy, excluding
skin cancers.
• Patients may not weigh more than the maximum weight limit for the PET /CT scanner
table (> 200 kg or 440 pounds).
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to 68Ga PSMA-11. Furosemide will not be administered to patients with
known allergy.
• Patients must not be claustrophobic.
• Written informed consent in accordance with federal, local, and institutional
guidelines. The patient must provide informed consent prior to the first screening
procedure.
• Previously treated (up to three prior lines of therapy), histologically proven
advanced squamous NSCLC.
• No prior treatment with EGFR inhibitors, IMIDs (eg, thalidomide, lenalidomide), or
anti-TNF antibodies.
• No treatment with systemic glucocorticoids within 3 weeks of initiation of study
therapy (topical and inhaled glucocorticoids are permitted).
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ and marrow function as defined below:
• absolute neutrophil count ≥ 1,000/μL
• platelets ≥ 50,000/μl
• total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SPGT) ≤ 2.5 X institutional upper limit of normal
• CrCl ≥ 45 ml/min
• For both male and female patients, effective methods of contraception must be used
throughout the study and for 3 months following the last dose of study treatment.
• Adequate archival tissue (5-10 slides) for correlative studies.
• Subject must have measurable disease per RECIST 1.1
Exclusion Criteria:
• Chemotherapy, radiotherapy, or other cancer therapy within two weeks prior to starting
study treatment. Subjects must have recovered from prior treatment-related to
toxicities to grade 1 or baseline (excluding alopecia and clinically stable toxicities
requiring ongoing medical management, such as hypothyroidism from prior immune
checkpoint inhibitor treatment).
• Subjects may not be receiving any other investigational agents for the treatment of
the cancer under study.
• Symptomatic brain metastases or brain metastases requiring escalating doses of
corticosteroids
• History of hypersensitivity or allergic reactions attributed to afatinib or
prednisone.
• Uncontrolled intercurrent illness including but not limited to poorly controlled
diabetes (which may worsen in setting of chronic prednisone therapy), symptomatic
congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric
illness/social situations that, in the opinion of the investigator, would limit
compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital
abnormalities and the potential of this regimen to harm nursing infants.
Drug: Afatinib + Prednisone
Lung/Thoracic, Advanced Squamous Non Small Cell Lung Cancer
UT Southwestern; Parkland Health & Hospital System
Study of Venetoclax in Combination With Carfilzomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma (MM)
A Phase 2, open-label, dose escalation study to evaluate the safety and efficacy of
venetoclax in combination with carfilzomib-dexamethasone (Kd) in participants with relapsed
or refractory MM and have received 1 to 3 prior lines of therapy.
Part 4 of this study is currently enrolling.
• Eastern Collaborative Oncology Group (ECOG) performance score of less than or equal to
2.
• Documented relapsed or progressive Multiple Myeloma (MM) on or after any regimen or is
refractory to the most recent line of therapy.
• Positive for translocation t(11;14) as determined by an analytically validated
Fluorescent In Situ Hybridization (FISH) assay per central laboratory testing.
• Received prior treatment with at least 1 prior line of therapy for MM.
• Measurable disease on Screening per International Myeloma Working Group (IMWG)
criteria.
• Meets absolute neutrophil count, platelet count, hemoglobin, liver and kidney function
laboratory values within 2 weeks prior to first dose of study drug.
Exclusion Criteria:
• Has a pre-existing condition that is contraindicated including.
• Non-secretory or oligo-secretory MM
• Active plasma cell leukemia.
• Waldenström's macroglobulinemia.
• Primary amyloidosis.
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein,
and skin changes).
• Active hepatitis B or C infection based on screening blood testing.
• Known active Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
infection.
• Significant cardiovascular disease.
• Major surgery within 4 weeks prior to first dose.
• Acute infections requiring antibiotic, antifungal or antiviral therapy within14
days prior to first dose.
• Peripheral neuropathy ≥ Grade 3 or ≥ Grade 2 with pain within 2 weeks prior to
first dose.
• Uncontrolled diabetes or uncontrolled hypertension within 14 days prior to first
dose.
• Any other medical condition that, in the opinion of the Investigator, would
adversely affect the participant's participation in the study.
• History of other active malignancies, including myelodysplastic syndrome (MDS), within
the past 3 years prior to study entry Other protocol defined inclusion/exclusion
criteria could apply
A Study to Evaluate the Effectiveness and Safety of CAEL-101 in Patients With Mayo Stage IIIa AL Amyloidosis
AL (or light chain) amyloidosis begins in the bone marrow where abnormal proteins misfold and
create free light chains that cannot be broken down. These free light chains bind together to
form amyloid fibrils that build up in the extracellular space of organs, affecting the
kidneys, heart, liver, spleen, nervous system and digestive tract.
The primary purpose of this study is to determine if CAEL-101 improves the overall survival
in Patients with cardiac AL Amyloidosis.
• Each patient must meet the following criteria to be enrolled in this study.
1. Be able to and provide written informed consent and be willing and able to comply
with all study procedures
2. Adult, 18 years and older
3. AL amyloidosis Mayo stage IIIa based on the 2013 European Modification of the
2004 Standard Mayo Clinic Staging in patients with advanced cardiac involvement
at the time of Screening
4. Measurable hematologic disease at Screening as defined by at least one of the
following:
1. Involved/Uninvolved Free Light Chain Difference (dFLC) > 4 mg/dL or
2. Involved Free Light Chain (iFLC) > 4 mg/dL with abnormal ratio or
3. Serum Protein Electrophoresis (SPEP) m-spike > 0.5 g/dL
5. Histopathological diagnosis of amyloidosis AND confirmation of AL derived amyloid
deposits by at least one of the following:
1. Immunohistochemistry or
2. Mass spectrometry or
3. Characteristic electron microscopy appearance
6. Cardiac involvement as defined by:
a. Documented clinical signs and symptoms supportive of a diagnosis of heart
failure in the setting of a confirmed diagnosis of AL amyloidosis in the absence
of an alternative explanation for heart failure AND b. At least one of the
following: i. Endomyocardial biopsy demonstrating AL cardiac amyloidosis or
ii. Echocardiogram demonstrating a mean left ventricular wall thickness
(calculated as [IVSd+LPWd]/2) of > 12 mm at diastole in the absence of other
causes (e.g., severe hypertension, aortic stenosis), which would adequately
explain the degree of wall thickening or
iii. Cardiac MRI with gadolinium contrast agent diagnostic or cardiac amyloidosis
7. Planned first-line treatment for plasma cell dyscrasia is a CyBorD-based regimen
administered as Standard of Care (SoC)
8. Adequate bone marrow reserve and hepatic function as demonstrated by:
1. Absolute neutrophil count ≥ 1.0 x 109/L
2. Platelet count ≥ 75 x 109/L
3. Hemoglobin ≥ 9 g/dL
4. Total direct bilirubin ≤ 2 times the upper limit of normal (x ULN) unless
due to Gilbert's syndrome.
5. Aspartate aminotransferase (AST) ≤ 3 x ULN
6. Alanine aminotransferase (ALT) ≤ 3 x ULN
7. Alkaline phosphatase (ALP) ≤ 5 x ULN (except for patients with hepatomegaly
and isozymes specific to liver, rather than bone)
9. Women of childbearing potential (WOCBP) must have a negative pregnancy test
during Screening and must agree to use highly effective physician approved
contraception from Screening to at least 5 months following the last study drug
administration or 12 months following the last dose of her PCD therapy, whichever
is longer
10. Men must be surgically sterile or must agree to use effective physician approved
contraception and refrain from donating sperm from Screening to at least 5 months
following the last study drug administration or 12 months following the last dose
of his PCD therapy, whichever is longer
Exclusion Criteria:
• Patients who meet any of the following criteria will not be permitted entry to the
study.
1. Have any other form of amyloidosis other than AL amyloidosis
2. Received prior therapy for AL amyloidosis or multiple myeloma. A maximum exposure
of 2 weeks of a CyBorD-based PCD treatment after screening laboratory samples are
obtained and prior to randomization is allowed.
3. Has POEMS syndrome or multiple myeloma defined as clonal bone marrow plasma cells
> 10% or biopsy-proven bony or extramedullary plasmacytoma AND any one or more of
the following CRAB features:
a. Evidence of end organ damage that can be attributed to the underlying plasma
cell proliferative disorder, specifically:
i. Hypercalcemia: serum calcium > 0.25 mmol/L (> 1mg/dL) higher than the ULN or >
2.75 mmol/L (> 11mg/dL)
ii. Renal insufficiency: creatinine clearance < 40 mL per minute or serum
creatinine > 177mol/L (> 2mg/dL)
iii. Anemia: hemoglobin value of > 20g/L below the lowest limit of normal, or a
hemoglobin value < 100g/L
iv. Bone lesions: one or more osteolytic lesion on skeletal radiography, CT, or
PET/CT. If bone marrow has < 10% clonal plasma cells, more than one bone lesion
is required to distinguish from solitary plasmacytoma with minimal marrow
involvement
OR
b. Any one of the following biomarkers of malignancy:
i. 60% or greater clonal plasma cells on bone marrow examination
ii. More than one focal lesion on MRI that is at least 5mm or greater in size
4. Have supine systolic blood pressure < 90 mmHg or symptomatic orthostatic
hypotension, defined as a decrease in systolic blood pressure upon standing of >
30 mmHg despite medical management (e.g., midodrine, fludrocortisones) in the
absence of volume depletion
5. Taking prednisone or its equivalent > 10 mg/day
6. Taking doxycycline
7. Receiving dialysis
8. Planned stem cell transplant during the first 6 months of protocol therapy. Stem
cell collection during the protocol therapy is permitted.
9. Have had myocardial infarction, uncontrolled angina, severe uncontrolled
ventricular arrhythmias within 6 months prior to screening or percutaneous
cardiac intervention with recent stent or coronary artery bypass grafting within
4 months prior to screening. Exacerbation of chronic condition or new acute
condition will require discussion and approval by the Medical Monitor.
10. Left Ventricular Ejection Fraction (LVEF) is < 40% by echocardiogram at Screening
11. Have severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area
< 1.0 cm2) or severe congenital heart disease
12. Have history of sustained ventricular tachycardia or aborted ventricular
fibrillation or a history of atrioventricular nodal or sinoatrial nodal
dysfunction for which a pacemaker/implantable cardioverter-defibrillator (ICD) is
indicated but not placed. (Participants who do have a pacemaker or ICD are
allowed in the study.)
13. QT corrected by Fridericia (QTcF) is > 550 msec. Participants who have a
pacemaker may be included regardless of calculated QTc interval.
14. There is evidence of acute ischemia or active conduction system abnormalities
with the exception of any of the following:
1. First degree Atrioventricular (AV)-block
2. Second degree AV-block Type 1 (Mobitz Type 1/Wenckebach type)
3. Right or left bundle branch block
4. Atrial fibrillation with a controlled ventricular rate. (An uncontrolled
ventricular rate [i.e., > 110 beats per minute] determined by an average of
three beats in lead II or representative beats in lead II is not allowed)
15. Have had major surgery within 4 weeks of randomization or is planning major
surgery during the study. Patients with surgical procedures conducted under local
anesthesia may participate
16. There is active malignancy (including lymphoma) with the exception of any of the
following:
1. Adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ
cervical cancer
2. Adequately treated stage I cancer from which the patient is currently in
remission and has been in remission for > 2 years
3. Low-risk prostate cancer with Gleason score < 7 and prostate-specific
antigen < 10 mg/mL
4. Other localized and/or low risk malignancies may be permitted with Medical
Monitor approval.
17. Have received an investigational drug/device in another clinical investigational
study within 60 days before Screening
18. Hypersensitivity to the study drug
19. Have received a live vaccine within 4 weeks prior to first dose of CyBorD
20. Women who are breast feeding
21. Have any other medical, social or psychological factors that could affect the
patient's safety or ability to consent personally or comply with study
procedures.
Mobile Health and Social Media Physical Activity Intervention Among Adolescent and Young Adult Childhood Cancer Survivors, the StepByStep Study
This phase III trial compares a multi-component mobile health and social media physical
activity intervention versus wearing a physical activity tracker alone among adolescent and
young adult childhood cancer survivors. Regular physical activity helps maintain healthy
weight, energy levels, and health. Adolescents and young adults who complete treatment for
cancer are often less active. They may gain weight and have more health problems compared to
people the same age who have not had treatment for cancer. Comparing the 2 programs will help
researchers learn how to increase physical activity levels over time and also how changes in
physical activity levels affect health and quality of life over time.
• First diagnosis of malignant neoplasm (International Classification of Diseases for
Oncology [ICD-O] behavior code of "3") in first and continuous remission at the time
of enrollment
• Curative cancer treatment must have included chemotherapy (including cellular therapy)
and/or radiation (including radioactive iodine)
• Note: Childrens Oncology Group (COG) therapeutic trial participation is not
required
• All cancer treatment must have been completed within 3-36 calendar months prior to
enrollment
• Patients must have a life expectancy of > 1 year
• Self-report of < 420 minutes of moderate-to-vigorous physical activity per week as
assessed via the study-specific Physical Activity Worksheet
• Note: See COG Study Web Page for the Godin-Shephard Leisure Time Physical
Activity Questionnaire or link to online calculator
• Ambulatory and no known medical contraindications to increasing physical activity
• Note: Patients with amputation, rotationplasty, or other prothesis are not
automatically excluded as long as they are ambulatory and have no known medical
contraindications to increasing physical activity and all other eligibility
criteria are satisfied
• No known significant physical or cognitive impairment that would prevent use of the
electronic devices used for the protocol intervention (e.g. Fitbit, smartphone,
tablet, or computer)
• Able to read and write English
• Note: For patients < 18 years, consenting parent/legal guardian does not have to
be able to read and write English
• All patients and/or their parents or legal guardians must sign a written informed
consent
• Note: Informed consent may be obtained electronically/online if allowed by local
site policy and Institutional Review Board (IRB)/Research Ethics Board (REB) of
record
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Exclusion Criteria:
• Post-menarchal female patients who are pregnant or planning to become pregnant in the
next year are excluded
• Note: Pregnancy status can be established by clinical history with patient.
Post-menarchal female patients are eligible as long as they agree to use an
effective contraceptive method (including abstinence) during study participation
• Patients with previous hematopoietic stem cell transplant (HSCT) are excluded
• Note: Patients with previous autologous HSCT, chimeric antigen receptor T-cell
(CAR T-cell) therapy, and other cellular cancer therapies can participate as long
as all other eligibility criteria are satisfied
Other: Educational Intervention, Device: FitBit, Other: Goal Setting, Other: Health Promotion and Education, Other: Media Intervention, Behavioral: Telephone-Based Intervention
Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm