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.
The Role of 68Gallium PSMA-11 in Enhancing Diagnosis of Primary and Metastatic Prostate Cancer
To goal of this research is to assess the ability of Gallium-68 (68Ga) Prostate-Specific
Membrane Antigen-11 (PSMA-11) positron emission tomography/computed tomography (PET/CT) to
increase diagnostic accuracy in localizing primary and metastatic lesions in patients with
suspected prostate cancer and elevated Prostate Imaging Reporting and Data System (PI-RADS)
scores and Prostate-Specific Antigen (PSA).
• Patients with suspected prostate cancer (e.g., abnormal digital rectal exam, elevated
and/or rising PSA) as determined by referring physician
• Patients must have had a diagnostic, standard of care mpMRI of the prostate with at
least one lesion with a PI-RADS v2.1 score ≥ 4
• In men with PI-RADS v2.1 score 4, PSA should be ≥ 10 ng/mL. In men with at least one
PI-RADS v2.1 score 5 lesion, there is no restriction on PSA level.
• Patients must be scheduled for biopsy or radical prostatectomy
• Patients should not have had any type of curative or palliative therapy for prostate
cancer before enrolling in the study
• Patients must be medically stable as judged by the patient's physician
• Patients must be able to lie still for a total of 60 minutes for the PET/CT scans
• Ability to understand and the willingness to sign a written informed consent
Exclusion Criteria:
• Patients who have had a prior prostatectomy or radiotherapy for prostate cancer cannot
participate in the study
• Patients who have had a prior biopsy for prostate cancer cannot participate in the
study
• Patients who have been treated for cancers other than skin cancers
• Subjects may not be receiving any other investigational agents for the treatment of
the cancer under study
• Patients may not weigh more than the maximum weight limit for the PET/CT scanner table
(>200 kilograms or 440 pounds)
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to 68Ga PSMA-11 or other agents used in the study such as gadolinium-based
intravenous contrast agent used during the mpMRI
• Prior TURP/BPH procedures, including steam/laser therapies
Trial of Curcumin to Prevent Progression of Low-risk Prostate Cancer Under Active Surveillance
This is a prospective study to determine if the use of curcumin randomized against placebo
will reduce cancer progression in patients with prostate cancer undergoing active
surveillance.
• Age between 40-89 years
• Biopsy proven, low-risk, localized prostate cancer (minimum of 8 cores)
• May have had biopsy within last 12 months ≤4 cores involved with cancer
• Gleason score ≤6 with no Gleason pattern 4
• Clinical stage T1c-T2a/b
• Serum PSA ≤15 ng/ml
• Life expectancy > 5 years
Exclusion Criteria:
• Any previous prostate cancer treatment (radiotherapy, chemotherapy, hormonal therapy,
oral glucocorticoids, GnRH analogues, prostatectomy)
• Concurrent or previous use within 6 months of screening of any 5α-reductase inhibitor
• Use of anabolic steroids or drugs with antiandrogenic properties
• Prostate volume >150 grams
• Patients who are taking antiplatelet, anticoagulant agents or have a history of a
bleeding disorder. Patients taking 81 mg of Aspirin will be allowed to enroll with
close observation
• History of gastric or duodenal ulcers or untreated hyperacidity syndromes. Patients on
stable doses (2 months of therapy) of GERD medication allowed.
• Patients who are currently taking Curcumin and are unwilling to stop or plan to take
Curcumin during the study
• Patients with a history of gallbladder problems or gallstones or biliary
obstruction,unless patient had cholecystectomy
Drug: Curcumin, Drug: Placebo
Prostate Cancer, Prostate
prostate cancer, active surveillance, curcumin
UT Southwestern; Parkland Health & Hospital System
Immunotherapy With Nivolumab and Ipilimumab Followed by Nivolumab or Nivolumab With Cabozantinib for Patients With Advanced Kidney Cancer, The PDIGREE Study
This phase III trial compares the usual treatment (treatment with ipilimumab and nivolumab
followed by nivolumab alone) to treatment with ipilimumab and nivolumab, followed by
nivolumab with cabozantinib in patients with untreated renal cell carcinoma that has spread
to other parts of the body. The addition of cabozantinib to the usual treatment may make it
work better. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may
help the body's immune system attack the cancer, and may interfere with the ability of tumor
cells to grow and spread. Cabozantinib may stop the growth of tumor cells by blocking some of
the enzymes needed for cell growth. It is not yet known how well the combination of
cabozantinib and nivolumab after initial treatment with ipilimumab and nivolumab works in
treating patients with renal cell cancer that has spread to other parts of the body.
• STEP I REGISTRATION CRITERIA
• Histologically documented renal cell carcinoma with clear cell component, including
patients who have sarcomatoid or rhabdoid features
• Any metastatic disease, including visceral, lymph node, other soft tissue and bone,
measurable per RECIST 1.1.
• Measurable disease as defined in the protocol.
• Must be intermediate or poor risk patient per International Metastatic Renal Cell
Carcinoma Database (IMDC) criteria (1 or more of the following): Karnofsky performance
status [KPS] < 80, < 1 year from diagnosis [including initial nephrectomy] to systemic
treatment for metastatic disease, hemoglobin less than lower limit of normal [LLN],
corrected calcium concentration greater than upper limit of normal [ULN], absolute
neutrophil count greater than ULN, platelet count > ULN).
• Central nervous system (CNS) disease permitted, if stable and not otherwise causing
symptoms or needing active treatment.
• Karnofsky performance status >= 70%.
• No prior treatment with PD-1, PD-L1, or CTLA-4 targeting agents (including but not
limited to nivolumab, pembrolizumab, pidilizumab, durvalumab, atezolizumab,
tremelimumab, and ipilimumab), or any other drug or antibody specifically targeting
T-cell co-stimulation or checkpoint pathways. The only exception is for prior
treatment with nivolumab or other PD-1/PD-L1/CTLA-4 targeting therapy on pre- or
post-operative trials, as long as > 1 year since completion of systemic therapy.
• No prior previous systemic therapy for renal cell carcinoma (prior HD IL-2 [> 28 days]
and prior adjuvant sunitinib > 180 days since completion and prior immunotherapy as
above are allowed).
• No systemic cancer therapy less than 28 days prior to registration; no radiation
therapy less than 14 days prior to registration. There must be a complete recovery and
no ongoing complications from radiotherapy.
• Not pregnant and not nursing, because this study involves an agent that has known
genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing
potential only, a negative serum or urine pregnancy test done =< 14 days prior to
registration is required.
• Age >= 18 years
• Absolute neutrophil count (ANC) >= 1,500/mm^3.
• Platelet count >= 100,000/mm^3.
• Hemoglobin >= 8 g/dL.
• Calculated (Calc.) creatinine clearance >= 30 mL/min.
• Urine protein =< 1+ or urine protein to creatinine (UPC) ratio < 1.
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (except for patients with known
or likely Gilbert's syndrome, for whom total bilirubin up to 3 mg/dL is allowed with
direct bilirubin =< 20% total bilirubin)
• Aspartate aminotransferase/alanine aminotransferase (AST/ALT) =< 2.5 x upper limit of
normal (ULN) or < 5 x ULN if hepatic metastases present.
• STEP 2 REGISTRATION ELIGIBILITY CRITERIA
• Successful completion of at least 1 cycle of ipilimumab/nivolumab.
• Resolution of any treatment-related adverse events to grade 1 or less per dose
modification section (this criteria does not include any adverse events [AEs] not
attributable to treatment which are present due to disease), with
prednisone-equivalent dosing at 10 mg daily or less. Exceptions for this criteria
include patients receiving replacement hormone treatments (such as levothyroxine for
treatment-related hypothyroidism or glucocorticoid replacement for adrenal
insufficiency). Please contact study chair if further discussion is needed.
• No more than 80 days from last dose of ipilimumab/nivolumab.
Exclusion Criteria:
• Active autoimmune disease requiring ongoing therapy.
• Ongoing acute toxicity > grade 2 from previous treatment.
• History of severe allergic, anaphylactic or other hypersensitivity reactions to
chimeric or humanized antibodies.
• Active hepatitis B/C, or active tuberculosis (PPD response without active TB is
allowed)
• Human immunodeficiency virus (HIV) -infected patients with detectable viral load
within 6 months prior to registration. Patients on effective anti-retroviral therapy
with undetectable viral load within 6 months prior to registration are eligible.
• Concurrent use of immunosuppressive medication including prednisone above 10 mg daily.
• Uncontrolled adrenal insufficiency.
• Uncontrolled hypertension (systolic blood pressure [BP] >150 mmHg or diastolic BP > 90
mmHg).
• Major surgery less than 28 days prior to registration.
• Any serious non-healing wound, ulcer, or bone fracture within 28 days prior to
registration.
• Any arterial thrombotic events within 180 days prior to registration.
• Clinically significant hematuria, hematemesis, or hemoptysis within 12 weeks prior to
registration.
• Cavitating pulmonary lesions or known endotracheal or endobronchial disease
manifestations.
• Lesions encasing or invading any major blood vessels (this does not include tumor
thrombus extending into/through renal vein/inferior vena cava [IVC]). Patients with
tumor thrombus extending into/through renal vein are considered eligible.
• Moderate of severe hepatic impairment (Child-Pugh B or C).
• Any history of untreated pulmonary embolism or deep venous thrombosis (DVT) in the 180
days prior to registration. (Any asymptomatic, treated pulmonary embolism or
asymptomatic, treated deep venous thrombosis > 30 days prior to registration allowed).
• Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms.
• Unstable cardiac arrhythmia within 6 months prior to registration.
• Any gastrointestinal (GI) bleeding =< 180 days, hemoptysis, or other signs of
pulmonary hemorrhage =< 90 days prior to registration.
• History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess,
bowel obstruction, or gastric outlet obstruction within 180 days prior to
registration.
• Active peptic ulcer disease, inflammatory bowel disease, or malabsorption syndrome
within 28 days prior to registration.
• Untreated hypothyroidism (treated hypothyroidism on thyroid replacement therapy is
allowed. Abnormal thyroid-stimulating hormone (TSH) is acceptable with normal T3/free
T4 if treated on thyroid replacement therapy)
• Evidence of pancreatitis, history of organ transplant, or history of congenital QT
syndrome.
• Active treatment with coumarin agents (e.g., warfarin), direct thrombin inhibitors
(e.g., dabigatran), direct Xa inhibitor betrixaban or platelet inhibitors (e.g.,
clopidogrel) within 5 days of registration. Allowed anticoagulants include:
prophylactic use of low-dose aspirin for cardio-protection (per local applicable
guidelines) and low-dose low molecular weight heparins (LMWH), therapeutic doses of
LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban,
apixaban. Allowed also in patients with known brain metastases who are on a stable
dose of the anticoagulant for at least 1 week prior to registration without clinically
significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• Significant cardiac ischemia events (ST elevation myocardial infarction [STEMI] or
non-ST elevation myocardial infarction [NSTEMI]) within 6 months or active NY Heart
Association class 3-4 heart failure symptoms
Clear Cell Renal Cell Carcinoma, Metastatic Malignant Neoplasm in the Bone, Sarcomatoid Renal Cell Carcinoma, Metastatic Malignant Neoplasm in the Soft Tissues, Stage IV Renal Cell Cancer AJCC v8, Metastatic Malignant Neoplasm in the Viscera, Metastatic Malignant Neoplasm in the Lymph Nodes
A Multi-Center Trial of Androgen Suppression With Abiraterone Acetate, Leuprolide, PARP Inhibition and Stereotactic Body Radiotherapy in Prostate Cancer (ASCLEPIuS)
The purpose of this study is to establish the maximum tolerable dose of niraparib when
combined with prostate stereotactic body radiotherapy (SBRT), abiraterone, leuprolide, and
prednisone (the phase 1 portion of the study) and determine 3-year biochemical PSA recurrence
free-survival with this treatment approach (the phase 2 portion of the study).
Inclusion Criteria
1. Pathologic biopsy proven adenocarcinoma of the prostate
2. At least one of the following criteria:
• cN1 on conventional or PET imaging
• Grade group 5
• Grade group 4 and PSA ≥10 ng/mL
• Grade group 3 and PSA ≥20 ng/mL
• High probability of Radiographic T3 on MRI AND Grade group ≥2
• Grade Group 3 AND PSA ≥10 ng/mL AND ≥50% positive biopsy cores
3. Age ≥ 18
4. ECOG < 1
5. Adequate organ and marrow function as defined per protocol.
6. Use of highly effective contraception (e.g. condoms) for the duration of treatment and
a minimum of 90 days thereafter. Men must also agree not to donate sperm for the
duration of the study participation, and for at least 90 days thereafter.
7. International Prostate Symptoms Score (IPSS) ≤ 20
8. Medically fit for treatment and agreeable to follow-up
9. Ability to understand and the willingness to sign a written informed consent
10. Tissue available for MiOncoSeq testing to assign DNA repair deficiency status
Exclusion Criteria
1. Clinical or radiographic evidence of distant metastatic disease by CT/bone scan
2. Clinical or radiographic evidence of high probability of clinical T4 disease
3. Prostate gland size >80 cc measured by ultrasound or MRI
4. Prominent median lobe assessed by treating physician
5. Lack of tissue from biopsy to be sent for correlative studies
6. Any prior treatment for prostate cancer (incudes TURP, chemotherapy, radiation
therapy, or anti-androgen therapy)
7. Prohibited within 30 days prior to administration to study treatment: spironolactone
and other investigational drug therapies.
8. Prohibited 3 months before participant registration and during administration of study
treatment: non-steroidal anti-androgens (e.g., bicalutamide, flutamide, nilutamide),
steroidal antiandrogens (megestrol acetate, cyproterone acetate), oral ketoconazole,
chemotherapy, immunotherapy, estrogens, radiopharmaceuticals.
9. History of prior pelvic radiation therapy
10. Concurrent treatment with strong CYP3A4 inducers such as phenytoin, carbamazepine,
rifampin, rifabutin, rifapentine, phenobarbital
11. Enrollment concurrently in another investigational drug study within 1 month of
registration
12. History of another active malignancy within the previous 3 years except for adequately
treated skin cancer or superficial bladder cancer
13. History of or active Crohn's disease or ulcerative colitis
14. Contraindication to or inability to tolerate MRIs
15. Patients with severe depression
16. Uncontrolled diabetes or known HbA1c>10
17. Any gastrointestinal disorder affecting absorption
18. Active pituitary or adrenal dysfunction
19. Patients with significant cardiovascular disease potentially including severe /
unstable angina, recent history of myocardial infarction, clinically significant heart
failure, cerebrovascular disease, venous thromboembolic events, clinically significant
arrhythmias)
20. Uncontrolled hypertension with persistently elevated systolic blood pressure >160
mmgHg or diastolic blood pressure >100 mmHg despite anti-hypertensive agents.
21. Prolonged QTc >450 ms or any ECG changes that interfere with QT interval
interpretation
22. Major surgery within 1 month of registration
23. History of myelodysplastic syndrome or leukemia
24. A known hypersensitivity to niraparib, abiraterone acetate, leuprolide, and/or
prednisone
25. Active infection or other medical condition that would be a contraindication to
prednisone use
26. Patients with known active hepatitis or chronic liver disease including cirrhosis
27. Any condition that in the opinion of the investigator would preclude participation in
this study
Pivotal Study of the NanoKnife System for the Ablation of Prostate Tissue (PRESERVE)
Pivotal study to evaluate the use of the NanoKnife System as a focal therapy option for
prostate cancer patients. This study will assess the safety and effectiveness of the device
when used to ablate prostate tissue in intermediate-risk prostate cancer patients.
1. Is greater than 50 years of age
2. Has at least a 10-year life expectancy
3. Has histologically confirmed organ-confined prostate cancer, clinical stage ≤ T2c
4. Has a PSA ≤ 15 ng/mL or PSA density < 0.2 ng/mL2 if PSA is > 15 ng/mL
5. Has Gleason score 3+4 or 4+3
6. Has no evidence of extraprostatic extension by mpMRI
7. Has no evidence of seminal vesicle invasion by mpMRI, and if suspected, confirmed by
biopsy
8. Physician is able to visualize prostate gland adequately on transrectal ultrasound
imaging during enrollment evaluation
9. Transperineal or transrectal targeted prostate biopsies of lesion, plus 10 core
systematic biopsies to include adequate sampling of the peripheral zone correlating
with an intermediate risk lesion in the area of the MR-visible lesion
10. A visible lesion on mpMRI that is accessible to Irreversible Electroporation (IRE)
treatment (Note: A non-MRI visible lesion detected via systematic standard biopsy will
not be considered an exclusion criterion provided the non-MRI visible lesion is
singularly located in the contralateral hemisphere of the prostate; is Gleason 6; and
comprises no more than 6 mm linear extent of prostate-bearing tissue in a single core
on standard biopsy)
11. Has signed a written informed consent and in the judgment of the physician, the study
is in the best interest of the subject
12. Understands and accepts the obligation and is logistically able to present for all
scheduled follow-up visits
Exclusion Criteria:
1. Has known hypersensitivity to pancuronium bromide, atricurium or cisatricurium
2. Is unfit for anesthesia or has a contraindication for agents listed for paralysis
3. Has an active urinary tract infection (UTI)
4. Has a history of bladder neck contracture
5. Is interested in future fertility
6. Has a history (within 3 years) of inflammatory bowel disease
7. Has a concurrent major debilitating illness
8. Had active treatment for a malignancy within 3 years, including malignant melanoma,
except for prostate cancer or other types of skin cancer
9. Has any active implanted electronic device (e.g., pacemaker)
10. Is unable to catheterize due to a urethral stricture disease
11. Has had prior or current prostate cancer therapies:
1. Biologic therapy for prostate cancer
2. Chemotherapy for prostate cancer
3. Hormonal therapy for prostate cancer within three months of procedure
4. Radiotherapy for prostate cancer
5. Surgery for prostate cancer
12. Has had prior transurethral prostatectomy (TURP), stricture surgery, urethral stent or
prostatic implants
13. Has had prior major rectal surgery (except hemorrhoids)
14. Is unfit for pelvic MRI scanning (e.g., severe claustrophobia, permanent cardiac
pacemaker, metallic implants that are likely to contribute significant image
artifacts, allergy or contraindication to gadolinium (to enhance MRI))
15. Is actively bleeding, is anticoagulated or on blood thinning medications, or has a
bleeding disorder
16. Is a member of a vulnerable population such as prisoners, handicapped or mentally
disabled persons, or economically or educationally disadvantaged persons
17. In the opinion of the treating physician, has a contraindication listed in the current
NanoKnife System User Manual (section 2.3)
• 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
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.
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.
A Comparison of TULSA Procedure vs. Radical Prostatectomy in Participants With Localized Prostate Cancer (CAPTAIN)
Men with localized, intermediate risk prostate cancer will be randomized to undergo either
radical prostatectomy or the TULSA procedure, with a follow-up of 10 years in this
multi-centered randomized control trial. This study will determine whether the TULSA
procedure is as effective and more safe compared to radical prostatectomy.
• Male
• Age 40 to 80 years, with >10 years life expectancy
• Biopsy-confirmed, NCCN (favorable and unfavourable) intermediate-risk prostate
acquired within last 12 months
• Stage ≤cT2c, N0, M0
• ISUP Grade Group 2 or 3 disease on TRUS-guided biopsy or in-bore biopsy
• PSA ≤20ng/mL within last 3 months
• Treatment-naïve
• Planned ablation volume is < 3 cm axial radius from urethra on mpMRI acquired within
last 6 months
Exclusion Criteria:
• Inability to undergo MRI or general anesthesia
• Suspected tumor is > 30 mm from the prostatic urethra
• Prostate calcifications is > 3 mm in maximum extent obstructing ablation of tumor
• Unresolved urinary tract infection or prostatitis
• History of proctitis, bladder stones, hematuria, history of acute urinary retention,
severe neurogenic bladder
• Artificial urinary sphincter, penile implant, or intraprostatic implant
• Patients who are otherwise not deemed candidates for radical prostatectomy
• Inability or unwillingness to provide informed consent
• History of anal or rectal fibrosis or stenosis, or urethral stenosis, or other
abnormality challenging insertion of devices
A Study of Abemaciclib (LY2835219) With Abiraterone in Men With Prostate Cancer That Has Spread to Other Parts of the Body and is Expected to Respond to Hormonal Treatment (Metastatic Hormone-Sensitive Prostate Cancer) (CYCLONE 3)
The purpose of this study is to learn whether adding abemaciclib to abiraterone plus
prednisone prolongs the time before prostate cancer gets worse. Participation may last
approximately 60 months.
• Adenocarcinoma of the prostate (as the predominant histology)
• High-risk metastatic hormone-sensitive prostate cancer. High risk is defined as:
• Greater than or equal to (≥)4 bone metastases by bone scan and/or
• ≥1 visceral metastases by computed tomography or magnetic resonance imaging
• Must have initiated androgen deprivation therapy (ADT) with luteinizing
hormone-releasing hormone (LHRH) agonist/antagonist or bilateral orchiectomy prior to
randomization. Up to 3 months of ADT prior to randomization is permitted with or
without first-generation anti-androgen.
• Adequate organ function
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Exclusion Criteria:
• Prior treatment with abemaciclib or any other cyclin dependent kinase 4 and 6 (CDK4 &
6) inhibitor
• Development of metastatic prostate cancer in the context of castrate levels of
testosterone
• Received any prior systemic therapy for metastatic prostate cancer (including
investigational agents), except for ADT and first-generation anti-androgen
• Clinically significant cardiovascular disease as evidenced by myocardial infarction,
arterial thrombotic events, or severe/unstable angina in the past 6 months, or New
York Heart Association Class II to IV heart failure
• History of syncope of cardiovascular etiology, ventricular arrhythmia of pathological
origin, or sudden cardiac arrest. Chronic and hemodynamically stable atrial arrhythmia
well-controlled on medical therapy is permitted
• Uncontrolled hypertension
• Clinically active or chronic liver disease, moderate/severe hepatic impairment
• Known untreated central nervous system (CNS) metastasis. Participants with a history
of treated brain metastases are eligible if stable for at least 8 weeks prior to
randomization and off corticosteroid for at least 2 weeks prior to randomization
Drug: Abemaciclib, Drug: Abiraterone, Drug: Prednisone or Prednisolone, Drug: Placebo for Abemaciclib
Study of TT-00420 Tablet as Monotherapy and Combination Therapy in Patients With Advanced Solid Tumors
This is a Phase Ib/II, multicenter, open-label study to evaluate the safety and preliminary
efficacy of TT-00420 tablet, as monotherapy or in combination regimens, in patients with
advanced solid tumors.
1. ≥ 18 years of age
2. Histopathological or cytologically documented locally advanced or metastatic solid
tumors who have no available standard therapeutic treatment options
3. At least one measurable lesion as defined by RECIST V1.1 criteria for solid tumors
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
5. Adequate organ function confirmed at screening and within 10 days of initiating
treatment, as evidenced by:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
• Hemoglobin (Hgb) ≥ 8 g/dl
• Platelets (plt) ≥ 75 x 10^9/L
• AST/SGOT and ALT/SGPT ≤ 2.5 x Upper Limit of Normal (ULN) or ≤ 5.0 x ULN if liver
metastases are present
• Total bilirubin ≤ 1.5 x ULN
• Calculated creatinine clearance ≥ 50 mL/min (Cockcroft Gault formula)
6. Negative pregnancy test within 72 hours before starting study treatment in all
premenopausal women and women < 12 months after the onset of menopause
7. Must agree to take sufficient contraceptive methods to avoid pregnancy during the
study and until at least 6 months after ceasing study treatment
8. Able to sign informed consent and comply with the protocol
Exclusion Criteria:
1. Women who are pregnant or lactating
2. Women of child-bearing potential (WOCBP) who do not use adequate birth control
3. Patients with any hematologic malignancy, including leukemia (any form), lymphoma, and
multiple myeloma
4. Patients with a history of primary central nervous system tumors or carcinomatous
meningitis.
5. Patients with the following mood disorders as judged by the Investigator or a
psychiatrist:
• Medically documented history of or active major depressive episode, bipolar
disorder (I or II), obsessive-compulsive disorder, schizophrenia; a history of
suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm
to others)
• ≥ CTCAE grade 3 anxiety
6. Impaired cardiac function or significant diseases, including but not limited to any of
the following:
• left ventricular ejection fraction (LVEF) < 45% as determined by multigated
acquisition (MUGA) scan or echocardiogram (ECHO)
• Congenital long QT syndrome
• QTcF ≥ 480 msec on screening ECG
• Unstable angina pectoris ≤ 3 months prior to starting study drug
• Acute myocardial infarction ≤ 3 months prior to starting study drug
7. Patients with:
• unresolved diarrhea ≥ CTCAE grade 2, or
• impairment of gastrointestinal (GI) function, or
• GI disease that may significantly alter the absorption of TT-00420
8. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.,
uncontrolled hypertension, uncontrolled hypertriglyceridemia, or active or
uncontrolled infection) that could cause unacceptable safety risks or compromise
compliance with the protocol
9. Patients who have received chemotherapy, targeted therapy, or immunotherapy ≤ 4 weeks
(6 weeks for nitrosourea or mitomycin-C) prior to starting study drug or who have not
recovered from side effects of such therapy
10. Patients who have received wide field radiotherapy ≤ 4 weeks or limited field
radiation for palliation ≤ 2 weeks prior to starting study drug or who have not
recovered from side effects of such therapy
11. Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or
who have not recovered from side effects of such therapy
12. Patients who have been treated with any hematopoietic colony-stimulating growth
factors (e.g., G-CSF, GM-CSF) ≤ 4 weeks prior to starting study drug.
13. Patients who are currently receiving treatment with therapeutic doses of warfarin
sodium or any other coumarin-derivative anticoagulants
14. Patients who have received systemic corticosteroids ≤ 2 weeks prior to starting study
drug or who have not recovered from the side effects of such treatment.
15. Patients who are currently receiving treatment with strong CYP3A inhibitors or
inducers ≤ 2 weeks prior to starting study drug.
16. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not
mandatory; patients with well controlled HIV might be enrolled)
17. Known history of active infection with Hepatitis B or Hepatitis C
18. Has received a live-virus vaccination within 30 days of planned first dose
19. Inability to swallow or tolerate oral medication
20. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that, in the opinion of the investigator, might confound the results of the trial,
interfere with the patient's safe participation and compliance in the trial.
Prostate Cancer, Sarcoma, Gastric Cancer, Bladder Cancer, Cholangiocarcinoma, Gallbladder Cancer, Thyroid Cancer, Triple Negative Breast Cancer, HER2-negative Breast Cancer, Advanced Solid Tumor, Breast - Female, Breast - Male, Lung/Thoracic, Other Digestive Organ, Other Skin, Other Urinary, Prostate, Stomach, Thyroid, Small Intestine, Small-cell Lung Cancer
A Study of Belzutifan (MK-6482) Plus Pembrolizumab (MK-3475) Versus Placebo Plus Pembrolizumab in Participants With Clear Cell Renal Cell Carcinoma Post Nephrectomy (MK-6482-022)
The purpose of this study is to assess the efficacy and safety of oral belzutifan (MK-6482)
plus intravenous (IV) pembrolizumab (MK-3475) compared to placebo plus pembrolizumab, in the
adjuvant treatment of Clear Cell Renal Cell Carcinoma (ccRCC) post nephrectomy.
The primary study hypothesis is that belzutifan plus pembrolizumab is superior to placebo
plus pembrolizumab with respect to disease-free survival (DFS).
The main inclusion and exclusion criteria include but are not limited to the following:
Inclusion Criteria:
• Has a histologically or cytologically confirmed diagnosis of RCC with clear cell
component per American Joint Committee on Cancer (AJCC) (8th Edition), with or without
sarcomatoid features
• Has intermediate-high risk, high risk, or M1 no evidence of disease (NED) RCC as
defined by the following pathological tumor-node metastasis and tumor grading:
1. Intermediate-high risk RCC: pT2, Grade 4 or sarcomatoid, N0, M0; pT3, any grade,
N0, M0
2. High risk RCC: pT4, any Grade N0, M0; pT any stage, any Grade, N+, M0
3. M1 NED RCC participants who present not only with the primary kidney tumor but
also solid, isolated, soft tissue metastases that can be completely resected at
one of the following: the time of nephrectomy (synchronous) or, ≤2 years from
nephrectomy (metachronous)
• Has undergone complete resection of the primary tumor (partial or radical nephrectomy)
and complete resection of solid, isolated, soft tissue metastatic lesion(s) in M1 NED
participants
• Must have undergone a nephrectomy and/or metastasectomy ≤12 weeks prior to
randomization
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 10
days before randomization.
• Male participants must agree to continue contraception at least 7 days after the last
dose of belzutifan/placebo
• Female participants of childbearing potential must be willing to use an adequate
method of contraception, for the course of the study through 120 days after the last
dose of pembrolizumab or at least 30 days after last dose of belzutifan/placebo,
whichever occurs last
• Has adequate organ function
Exclusion Criteria:
• Has had a major surgery, other than nephrectomy plus resection of preexisting
metastases for M1 NED participants, within 4 weeks prior to randomization
• Has a pulse oximeter reading <92% at rest, requires intermittent supplemental oxygen,
or requires chronic supplemental oxygen
• Has clinically significant cardiovascular disease within 6 months from first dose of
study intervention
• Has other clinically significant disorders such as: serious active nonhealing
wound/ulcer/bone fracture; requirement for hemodialysis or peritoneal dialysis
• Has preexisting brain or bone metastatic lesions
• Has received prior systemic therapy for RCC
• Has received prior radiotherapy for RCC
• Has received a live or live-attenuated vaccine within 30 days before the first dose of
study intervention; administration of killed vaccines are allowed
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
• Has a known additional malignancy (other than RCC treated with nephrectomy and/or
metastasectomy) that is progressing or has required active treatment within the past 3
years
• Has an active autoimmune disease that has required systemic treatment in past 2 years
(i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive
drugs); replacement therapy is allowed
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required
steroids or has current pneumonitis/interstitial lung disease
• Has an active infection, requiring systemic therapy
• Has a known history of human immunodeficiency virus (HIV) infection, a known history
of Hepatitis B or known active Hepatitis C virus infection
• Has had an allogenic tissue/solid organ transplant
1. Subject is able and willing to comply with all the assessments of the study,
2. Subject or subject's legal representative has been informed of the nature of the
study, agrees to participate and has signed the informed consent form,
3. ≥ 45 years of age,
4. Baseline IPSS score ≥ 13; ≥ 1 in the IPSS voiding to storage sub-score ratio
(IPSS-V/S),
5. Prostate volume 25 •80 cc by transrectal ultrasound (TRUS), measured within 120 days
post study consent,
6. Prostatic urethral length between 25 and 45 mm, as measured by cystoscopic pull-back,
7. Failed, intolerant, or subject choice to not take a medication regimen for the
treatment of LUTS.
Exclusion Criteria:
1. Obstructive intravesical median prostatic lobe as determined by ultrasound (i.e., more
than 10 mm intravesical prostatic protrusion on sagittal mid-prostate plane via
abdominal ultrasound),
2. High bladder neck with the absence of lateral lobe encroachment indicating a high
likelihood of primary bladder neck obstruction as determined by the Investigator,
3. Urethral stricture, meatal stenosis, or bladder neck stricture •either current or
recurrent,
4. Anatomical anomalies that will not accommodate the Implant, as determined by
cystoscopy (e.g., prostatic urethral length to height geometry),
5. Requires indwelling catheter or intermittent catheterization to void,
6. Baseline PSA > 10 ng/mL or confirmed or suspected prostate cancer (Subjects with a PSA
level above 2.5 ng/mL, or age specific, or local reference ranges should have prostate
cancer excluded to the Investigator's satisfaction),
7. One of the following baseline test results, taken from a single uroflowmetry reading:
1. Urinary volume void ≤ 125mL (pre-bladder urinary volume of ≥ 150 mL required),
2. Peak urinary flow rate (Qmax) of ≤ 5 ml/second or > 15 mL/second,
3. Post- void residual volume (PVR) > 250 mL
8. History of other diseases causing voiding dysfunction including urinary retention
(e.g., uncontrolled diabetes, diagnosis of neurogenic bladder, Parkinson's disease,
multiple sclerosis, etc.),
9. Subjects with overactive bladder in the absence of benign prostatic obstruction,
10. Acute urinary tract infection (UTI) or finding of asymptomatic bacteriuria (Note:
subject can be enrolled if the UTI is treated and followed with a negative urine test
result), or subjects with history of recurrent UTIs (defined as > 3 UTIs in the past
12 months),
11. Concomitant bladder stones,
12. Previous pelvic irradiation or radical pelvic surgery,
13. Previous prostate surgery, including: enucleation, resection, vaporization,
thermotherapy, ablation, stenting or prostatic urethral lift,
14. Chronic prostatitis, recurrent prostatitis, chronic pelvic pain syndrome (CPPS), or
painful bladder syndrome within the past 12 months
15. Known allergy to nickel,
16. Life expectancy less than 60 months,
17. Use of concomitant medications (e.g., anticholinergics, antispasmodics or tricyclic
antidepressants) affecting bladder function,
18. Inability to stop taking anticoagulants and/or antiplatelets for at least 3 days prior
to the procedure or coumadin for at least 5 days prior to the procedure (Note: low
dose aspirin therapy (81 mg) is permitted),
19. Taking 5-alpha-reductase inhibitors within 3 months of baseline evaluation,
20. Taking one of the following within 2 weeks of baseline evaluation:
1. alpha-blockers,
2. imipramine,
3. anticholinergics,
4. cholinergic gonadotropin releasing hormonal analogues,
5. Phosphodiesterase-5 Enzyme Inhibitors (Tadalafil) in doses for BPH,
6. Beta-3 adrenergic receptor agonist (Mirabegron),
21. Taking androgens, unless eugonadal state for at least 3 months or greater as
documented by the Investigator,
22. Taking one of the following within 24 hours of pre-treatment (baseline) evaluation:
1. phenylephrine, or,
2. pseudoephedrine,
23. Future fertility concerns, or,
24. In the Investigator's opinion, the subject has a physical, psychological, or medical
impairment that might prevent study completion or would confound study results
(including subject questionnaires).
Device: Zenflow Spring System, Device: Sham Procedure
RAdium-223 and SABR Versus SABR for Oligometastatic Prostate Cancers (RAVENS)
This is a Phase II non-blinded randomized study evaluating men with oligometastatic prostate
cancer lesions randomized (1:1) to stereotactic ablative radiation therapy (SABR) versus SBAR
+ Radium-223. We are looking to determine the progression-free survival of men who have
oligometastatic prostate cancer with at least one bone metastasis with stereotactic ablative
radiation therapy (SABR) versus SABR + Radium-223.
• Patient must have at least one and up to three asymptomatic metastatic tumor(s) of the
bone or soft tissue (with at least one bone metastasis) develop within the past
6-months that are ≤ 5.0 cm or <250 cm3
• Patient must have had their primary tumor treated with surgery and/or radiation.
• Histologic confirmation of malignancy (primary or metastatic tumor).
• PSADT <15 months. PSA doubling time (PSADT) will be calculated using as many PSA
values that are available from time of relapse (PSA > 0.2). To calculate PSADT, the
Memorial Sloan Kettering Cancer Center Prostate Cancer Prediction Tool will be used.
It can be found at the following web site:
https://www.mskcc.org/nomograms/prostate/psa-doubling-time.
• Patient may have had prior systemic therapy and/or ADT associated with treatment of
their primary prostate cancer. Patient may have had ADT associated with salvage
radiation therapy (to the primary prostate cancer or pelvis is allowed).
• PSA > 0.5 but <50.
• Testosterone > 125 ng/dL.
• Patient must be ≥ 18 years of age.
• Patient must have a life expectancy ≥ 12 months.
• Patient must have an ECOG performance status ≤ 2.
• Patient must have normal organ and marrow function as defined as:
Before the first administration of Xofigo, the absolute neutrophil count (ANC) should be ≥
1.5 x 109/L, the platelet count ≥ 100 x 109/L and hemoglobin ≥ 10 g/dL.
* Patient must have the ability to understand and the willingness to sign a written
informed consent document.
Exclusion Criteria:
• No more than 3 years of ADT is allowed, with the most recent ADT treatment having
occurred greater than 6 months prior to enrollment.
• PSMA-PET/MRI or PSMA-PET/CT scan within the past 6 months with results that
demonstrate more disease lesions than baseline CT/Bone Scan
• Castration-resistant prostate cancer (CRPC).
• Spinal cord compression or impending spinal cord compression.
• Suspected pulmonary and/or liver metastases (greater >10 mm in largest axis).
• Patient receiving any other investigational agents.
• Patient receiving abiraterone and prednisone.
• Patient is participating in a concurrent treatment protocol.
• Serum creatinine > 3 times the upper limit of normal.
• Total bilirubin > 3 times the upper limit of normal.
• Liver Transaminases > 5-times the upper limit of normal.
• Unable to lie flat during or tolerate PET/MRI, PET/CT or SBRT.
• Prior salvage treatment to the primary prostate cancer or pelvis is allowed.
• Refusal to sign informed consent.
An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With SoC, Versus SoC Alone, in Adult Male Patients With mHSPC (PSMAddition)
The purpose of this study is to evaluate the efficacy and safety of 177Lu-PSMA-617 in
combination with Standard of Care, versus Standard of Care alone, in adult male patients with
mHSPC. In this study, the SoC is defined as a combination of Androgen Receptor Directed
Therapy + Androgen Deprivation Therapy. Approximately 1126 patients will be randomized in
this study.
Participants eligible for inclusion in this study must meet all of the following criteria:
1. Signed informed consent must be obtained prior to participation in the study
2. Patients must be adults ≥18 years of age
3. Patients must have an ECOG performance status of 0 to 2
4. Patients must have a life expectancy >9 months as determined by the study investigator
5. Patients must have metastatic prostate cancer with histologically or cytologically
confirmed adenocarcinoma (current or prior biopsy of the prostate and/or metastatic
site)
6. Patients must have evidence of PSMA-positive disease as seen on a 68Ga-PSMA-11 PET/CT
scan, and eligible as determined by the sponsor's central reader
7. Patients must have at least one documented metastatic bone and/or soft tissue/visceral
lesion documented in the following manners within 28 days prior randomization:
1. Metastatic disease to the bone (in any distribution) visible on 99Tc-MDP bone
scintigraphy on either pre-ADT scans or baseline scans AND/OR
2. Lymph node metastases of any size or distribution. If lymph nodes are the only
site of metastasis, then at least one must be at least 1.5 cm in short axis AND
outside of the pelvis AND/OR
3. Visceral metastases of any size or distribution. If a participant has a history
of visceral metastases at any time prior to randomization, he should be coded as
having visceral metastases at baseline (i.e., patients with visceral metastases
prior to ADT that disappear at baseline will be counted as having visceral
metastases and would therefore have high volume disease for stratification
purposes).
8. Patients must have adequate organ function:
• Bone marrow reserve ANC ≥1.5 x 109/L Platelets ≥100 x 109/L Hemoglobin ≥9 g/dL
• Hepatic Total bilirubin ≤2 x the institutional upper limit of normal (ULN). For
patients with known Gilbert's Syndrome ≤3 x ULN is permitted Alanine
aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3.0 x ULN OR ≤5.0 x
ULN for patients with liver metastases
• Renal eGFR ≥ 50 mL/min/1.73m2 using the Modification of Diet in Renal Disease
(MDRD) equation
9. Albumin ≥2.5 g/dL
10. Human immunodeficiency virus (HIV)-infected patients who are healthy and have a low
risk of acquired immune deficiency syndrome (AIDS)-related outcomes can participate in
this trial
11. Patients must be:
Treatment naïve OR minimally treated with:
• Up to 45 days of luteinizing hormone-releasing hormone (LHRH) agonist /antagonists or
bilateral orchiectomy with or without first generation anti-androgen (e.g.
bicalutamide, flutamide) for metastatic prostate cancer is allowed prior to ICF
signature. If given, first generation anti-androgen must be discontinued prior to
start of study therapy or after 45 days whatever happens first.
• If received, prior LHRH agonist/antagonist with or without first generation
anti-androgen use in the adjuvant/neo-adjuvant setting must have been discontinued >
12 months prior to ICF signature AND must not have exceeded 24 months of therapy AND
must not have shown disease progression within 12 months of completing
adjuvant/neo-adjuvant therapy.
• Up to 45 days of CYP17 inhibitor or ARDT exposure for metastatic prostate cancer is
allowed prior to ICF signature. No CYP17 inhibitor or ARDT exposure for earlier stages
of prostate cancer is allowed.
Exclusion Criteria:
Participants meeting any of the following criteria are not eligible for inclusion in this
study.
1. Participants with rapidly progressing tumor that requires urgent exposure to
taxane-based chemotherapy
2. Any prior systemic anti-prostate cancer therapy (with the exception of the drugs
listed on inclusion criteria 11), including chemotherapy, Poly (adenosine
diphosphate-ribose) polymerase (PARP) inhibitors, immunotherapy or biological therapy
(including monoclonal antibodies).
3. Concurrent cytotoxicity chemotherapy, immunotherapy, radioligand therapy, PARP
inhibitor, biological therapy or investigational therapy
4. Previous treatment with any of the following within 6 months of randomization:
Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body
irradiation. Previous PSMA-targeted radioligand therapy is not allowed
5. Ongoing participation in any other clinical trial
6. Use of other investigational drugs within 30 days prior to day of randomization
7. Known hypersensitivity to any of the study treatments or its excipients or to drugs of
similar chemical classes
8. Transfusion for the sole purpose of making a participant eligible for study inclusion
9. Participants with CNS metastases that are neurologically unstable, symptomatic, or
receiving corticosteroids for the purpose of maintaining neurologic integrity.
Participants with epidural disease, canal disease and prior cord involvement are
allowed if those areas have been treated, are stable, and not neurologically impaired.
Participants with parenchymal CNS metastasis (or a history of CNS metastasis), that
have received prior therapy and are neurologically stable, asymptomatic and not
receiving steroids for CNS metastases, are allowed, baseline and subsequent
radiological imaging must include evaluation of the brain (magnetic resonance imaging
(MRI) preferred or CT with contrast).
10. Diagnosed with other malignancies that are expected to alter life expectancy or may
interfere with disease assessment. However, participants with a prior history of
malignancy that has been adequately treated and who have been disease free, treatment
free for more than 3 years prior to randomization, or participants with adequately
treated non-melanoma skin cancer, superficial bladder cancer are eligible.
11. Concurrent serious (as determined by the Principal Investigator) medical conditions,
including, but not limited to, uncontrolled infection, known active hepatitis B or C,
or other significant co-morbid conditions that in the opinion of the investigator
would impair study participation or cooperation. Participants with an active
documented COVID-19 infection (any grade of disease severity) at time of informed
consent may be included only when completely recovered (in accordance with local
guidance).
12. Active clinically significant cardiac disease defined as any of the following:
• NYHA class 3/4 congestive heart failure within 6 months prior to ICF signature
unless treated with improvement and echocardiogram or MUGA demonstrates EF > 45%
with improvement in symptoms to class < 3.
• History or current diagnosis of ECG abnormalities indicating significant risk of
safety for participants in the study such as: Concomitant clinically significant
cardiac arrhythmias, e.g. sustained ventricular tachycardia, complete left bundle
branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block,
Mobitz type II and third degree AV block)
• History of familial long QT syndrome or known family history of Torsades de
Pointes
• Cardiac or cardiac repolarization abnormality, including any of the following:
History of myocardial infarction (MI), angina pectoris, or coronary artery bypass
graft (CABG) within 6 months prior to ICF signature
13. History of somatic or psychiatric disease/condition that may interfere with the
objectives and assessments of the study
14. Symptomatic cord compression, or clinical or radiologic findings indicative of
impending cord compression
15. Any condition that precludes raised arms position
16. Unmanageable concurrent bladder outflow obstruction or urinary incontinence. Note:
participants with bladder outflow obstruction or urinary incontinence, which is
manageable and controlled with best available standard of care (incl. pads, drainage)
are allowed.
17. Sexually active males unwilling to use a condom during intercourse while taking study
treatment and for 14 weeks after stopping study treatment. A condom is required for
all sexually active male participants to prevent them from fathering a child AND to
prevent delivery of study treatment via seminal fluid to their partner. In addition,
male participants must not donate sperm for the time period specified above. If local
regulations deviate from the contraception methods listed above to prevent pregnancy,
local regulations apply and will be described in the ICF
Testing the Addition of a New Anti-cancer Drug, Radium-223 Dichloride, to the Usual Treatment (Cabozantinib) for Advanced Renal Cell Cancer That Has Spread to the Bone, the RadiCaL Study
This phase II trial studies whether adding radium-223 dichloride to the usual treatment,
cabozantinib, improves outcomes in patients with renal cell cancer that has spread to the
bone. Radioactive drugs such as radium-223 dichloride may directly target radiation to cancer
cells and minimize harm to normal cells. Cabozantinib may stop the growth of cancer cells by
blocking some of the enzymes needed for cell growth. Giving radium-223 dichloride and
cabozantinib may help lessen the pain and symptoms from renal cell cancer that has spread to
the bone, compared to cabozantinib alone.
• Documented histologic or cytologic diagnosis of renal cell cancer (RCC). All subtypes
of RCC are eligible including but not limited to clear cell, papillary, chromophobe,
translocation, collecting duct carcinoma, medullary carcinoma, and unclassified
categories. Enrollment of non-clear cell patients will be limited to 20% of the total
sample size (~ 42 patients). Once this goal is met, accrual of non-clear cell patients
will be discontinued (a notice will be sent out 2 weeks in advance). Sarcomatoid and
rhabdoid differentiation are allowed
• Presence of at least 1 metastatic bone lesion not treated with prior radiation is
required.
• The presence of bone metastases can be detected by computed tomography (CT),
magnetic resonance imaging (MRI), Tc-99m bone scan or positron emission
tomography (PET) (fludeoxyglucose F-18 [FDG] or sodium fluoride [NaF]) imaging.
Patients with non-measurable bone-only disease are allowed. Patients may have
received prior radiation therapy for bone metastases or other external radiation
>= 7 days prior to registration, as long as they still have at least 1 metastatic
bone lesion not treated with radiation. Patients with visceral metastases are
allowed, as long as they have at least one untreated bone metastases
• No prior treatment with cabozantinib
• No treatment with any type of small molecular kinase inhibitor (including
investigational kinase inhibitors) within 2 weeks or 5 half-lives (whichever is
shorter) of registration or receipt of any anti-cancer therapy (including
investigational therapy, monoclonal antibodies, cytokine therapy) within 3 weeks of
registration
• No prior hemibody external radiotherapy
• No prior therapy with radium-223 dichloride or systemic radiotherapy (such as
samarium, strontium)
• No major surgery within 6 weeks of randomization. Procedures such as thoracentesis,
paracentesis, percutaneous biopsy, Moh's or other topical skin surgery, Lasik eye
surgery are not considered major surgery. Patients who have had a nephrectomy may be
registered >= 3 weeks after surgery, providing there are no wound-healing
complications. Subjects with clinically relevant ongoing complications from prior
surgery are not eligible
• Recovery to baseline or =< grade 1 CTCAE version 5.0 from toxicity related to any
prior treatment, unless adverse events are clinically nonsignificant and/or stable on
supportive therapy
• The use of osteoclast targeted therapy including either bisphosphonates or denosumab
is mandated on this study except in patients with contraindications as determined by
the treating investigator, including:
• Hypocalcemia
• Hypophosphatemia
• Renal impairment including those with a glomerular filtration rate (GFR) < 35
mL/min using the Cockcroft-Gault equation or acute renal impairment
• Hypersensitivity to drug formulation
• Dental condition or need for dental intervention that per the investigator
would increase the risk of osteonecrosis of jaw (ONJ).
• Use of osteoclast targeted therapy or reason against use needs to be
recorded in the electronic case report form (eCRF). Additionally, reason for
discontinuation of osteoclast targeted therapy need to be appropriately
documented in the eCRF
• Not pregnant and not nursing, because this study involves an investigational agent
whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn
are unknown.
• Therefore, for women of childbearing potential only, a negative urine pregnancy
test done =< 28 days prior to registration is required. A female of childbearing
potential is a sexually mature female who: 1) has not undergone a hysterectomy or
bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least
12 consecutive months (i.e., has had menses at any time in the preceding 12
consecutive months)
• Karnofsky performance status >= 60%
• No brain metastases or cranial epidural disease unless adequately treated with
radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks prior to
registration as documented by MRI or CT imaging or deemed stable by clinical
investigator. Treated brain metastases are defined as having no ongoing requirement
for steroids and no evidence of progression or hemorrhage after treatment for at least
4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by
clinical investigator
• No imminent or established spinal cord compression based on clinical symptoms and/or
imaging. In patients with untreated imminent or established spinal cord compression,
treatment with standard of care as clinically indicated should be completed at least 2
weeks before registration
• No imminent or impending pathologic fracture based on clinical symptoms and/or
imaging. In patients with untreated imminent or impending pathologic fracture,
treatment with standard of care as clinically indicated should be completed at least 2
weeks before registration
• No significant, uncontrolled intercurrent or recent illness, including but not limited
to the following conditions:
• Cardiovascular disorders: Symptomatic congestive heart failure, unstable angina
pectoris, serious cardiac arrhythmia; uncontrolled hypertension defined as
sustained blood pressure > 150 mm Hg systolic or > 100 mm Hg diastolic despite
optimal antihypertensive treatment; stroke (including transient ischemic attack),
myocardial infarction, or other ischemic event, within 6 months before
randomization; thromboembolic event (e.g., deep venous thrombosis, pulmonary
embolism) within 1 month before randomization
• Gastrointestinal disorders: Disorders associated with a high risk of perforation
or fistula formation: active inflammatory bowel disease, active diverticulitis,
active cholecystitis, active symptomatic cholangitis or active appendicitis,
active acute pancreatitis or active acute obstruction of the pancreatic or
biliary duct, or active gastric outlet obstruction; abdominal fistula,
gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess
within 3 months before randomization. Note: Complete healing of an
intra-abdominal abscess must be confirmed before randomization
• No clinically significant hematuria, hematemesis, or hemoptysis, or other history
of significant bleeding (e.g., pulmonary hemorrhage) within 3 months before
randomization
• No lesions invading major pulmonary blood vessels
• No other clinically significant disorders:
• Human immunodeficiency virus (HIV)-infected patients on effective
anti-retroviral therapy (with no medications prohibited by this protocol
[e.g. drug-drug interactions]) with undetectable viral load within 6 months
are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the
HBV viral load must be undetectable on suppressive therapy (with no
medications prohibited by this protocol [e.g. drug-drug interactions]), 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
(with no medications prohibited by this protocol [e.g. drug-drug
interactions])
• No serious non-healing wound or ulcer
• No malabsorption syndrome
• No uncompensated/symptomatic hypothyroidism
• No moderate to severe hepatic impairment (Child-Pugh B or C)
• No requirements for hemodialysis or peritoneal dialysis
• No history of solid organ transplantation
• No chronic concomitant treatment with strong CYP3A4 inducers or inhibitors. Because
the list of these agents is constantly changing, it is important to regularly consult
a frequently updated medical reference. Patients may not have received a strong CYP3A4
inducer within 12 days prior to registration nor a strong CYP3A4 inhibitor within 7
days prior to registration
• No concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin
inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet
inhibitors (e.g., clopidogrel). Allowed anticoagulants include:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable
guidelines) and low-dose low molecular weight heparins (LMWH).
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors
rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who
are on a stable dose of the anticoagulant for at least 1 week before first dose
of study treatment without clinically significant hemorrhagic complications from
the anticoagulation regimen or the tumor.
• Absolute neutrophil count (ANC) >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• Hemoglobin >= 9 g/dl (transfusions allowed)
• Calculated (calc.) creatinine clearance >= 30 mL/min using the Cockcroft-Gault
equation
• Total bilirubin =< 1.5 x upper limit of normal (ULN), for patients with Gilberts
disease =< 3.0 x ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x ULN
• Urine protein to creatinine (UPC) ratio =< 2 mg/mg OR 24-hr urine protein < 2 g
[18F]PT2385 PET/CT in Patients With Renal Cell Carcinoma
This is an exploratory study to assess [18F]PT2385 Positron Emission Tomography/Computed
Tomography (PET/CT) in patients with renal cell carcinoma (RCC). This is an open-label,
nontherapeutic trial. The main objective is to correlate hypoxia-inducible factor-2alpha
(HIF2α) levels as determined by an investigational [18F]PT2385 PET/CT scan with the levels on
subsequently obtained tissue by HIF2α immunohistochemistry (IHC). There will be three
cohorts. The first pre-surgical cohort will have [18F]PT2385 PET/CT prior to nephrectomy. The
uptake and retention on Positron Emission Tomography (PET), quantified as standardized uptake
value (SUV) max and mean, abbreviated SUV henceforth will be correlated with HIF2α levels by
IHC on the primary tumor. The second cohort will comprise patients with metastatic clear cell
renal carcinoma (ccRCC). SUV will be correlated with HIF2α levels measured by IHC on a biopsy
sample from a metastasis. Both low- and high-avidity sites will be biopsied and tracer uptake
correlated with HIF2α IHC. A third cohort will include patients with Von Hippel-Lindau (VHL)
syndrome and any of the following disease manifestations - RCC, central nervous system (CNS)
hemangioblastoma, and/or pancreatic neuroendocrine tumor(s). Investigational imaging will
evaluate HIF2α expression within a tumor type and across different tumor types. A biopsy is
encouraged but not mandatory for this cohort.
• Ability to understand and the willingness to sign a written informed consent that
includes study interventions (PET/CT and, if cohort 2, mandatory biopsy).
• Ability to lie still for a 30- to 60-minute PET/CT scan.
• One of the following:
1. Cohort 1. Patients with suspected RCC planned for surgery.
2. Cohort 2. Patients with metastatic ccRCC or VHL syndrome and RCC. Biopsy is
required (planned resection for treatment reasons of a metastatic site is
acceptable in lieu of the biopsy).
3. Cohort 3. Patients with VHL syndrome with RCC, CNS hemangioblastoma, and/or
pancreatic neuroendocrine tumor(s) planning to start belzutifan.
• Women of child-bearing potential must agree to undergo and have documented a negative
pregnancy test on the day of [18F]PT2385 administration. A female of child-bearing
potential is any woman (regardless of sexual orientation, having undergone a tubal
ligation, or celibate by choice) who meets the following criteria:
1. Has not undergone a hysterectomy or bilateral oophorectomy; or
2. Has not been naturally postmenopausal for at least 12 consecutive months (i.e.,
has had menses at any time in the preceding 12 consecutive months).
Exclusion Criteria:
• 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.
• Claustrophobia or 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 kilograms or 440 pounds).
• For cohort 2 patients, lack of suitable sites for mandatory biopsy. For example,
patients with metastatic disease restricted to the lungs that would require
percutaneous biopsies with associated risk of bleeding and pneumothorax will be
excluded.