Prostate Cancer

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Phase III Randomized Trial of Standard Systemic Therapy (SST) Versus Standard Systemic Therapy Plus Definitive Treatment (Surgery or Radiation) of the Primary Tumor in Metastatic Prostate Cancer


Condition: Castration Levels of Testosterone, Metastatic Prostatic Adenocarcinoma, Stage IV Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03678025

Sponsor: Southwest Oncology Group

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  • 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.

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Cystoprostatectomy Versus Radiotherapy Combined With Androgen Deprivation Therapy for the Treatment of Clinical T4 Prostate Cancer With Bladder Invasion: a Multicentre, Prospective, Open, Randomized Clinical Trial


Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03482089

Sponsor: Tongji Hospital

Eligibility:

  • Age: minimum 18 Years maximum 75 Years
  • Gender: Male

Inclusion Criteria:

  1. Age ≤75, at the time of randomization
  2. Newly diagnosed primary prostatic adenocarcinoma confirmed by pathological examination of biopsy;diagnosed within 6 months prior to randomization
  3. Untreated for surgery, radiotherapy, or androgen deprivation therapy
  4. Eastern Cooperative Oncology Group (ECOG) performance status 0- 2; American Standards Association (ASA) classification I-III
  5. A life expectation of at least 10 years
  6. Tumor stage (T, M, N): Clinical T4N0M0 with bladder invasion (confirmed by MRI)
  7. Eligible for either treatment of cystoprostatectomy or radiotherapy
  8. Signed informed consent should be obtained from both the patient or one authorized legal relative.

Exclusion Criteria:

  1. Patients with a history of other cancer diagnoses except non-melanoma skin cancer
  2. Patients with pelvic surgery
  3. Patients with severe systemic diseases
  4. severe kidney function -glomerular filtration rate (GFR) < 30 ml/min or elevated liver transaminases above > 10 upper limit of normal (ULN)
  5. Patients who are not able comply with scheduled follow-up visits and examinations with the consideration of patients' physical or mental condition

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A Randomized, Double-blind, Placebo-controlled, Phase 3 Study of Apalutamide in Subjects With High-risk, Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy


Condition: Prostatic Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03767244

Sponsor: Janssen Research & Development, LLC

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the prostate
  • High-risk disease defined by a total Gleason Sum Score greater than equal to (>=) 4+3 (=Grade Groups [GG] 3 5) and >=1 of the following 4 criteria: a) Any combination of Gleason Score 4+3 (= 3) and Gleason Score 8 (4+4 or 5+3) in >= 6 systematic cores (with >=1 core Gleason Score 8 [4+4 or 5+3] included); b) Any combination of Gleason Score 4+3 (=GG 3) and Gleason Score 8 (4+4 or 5+3) in >=3 systematic cores and Prostate-specific antigen (PSA) >=20 ng/mL (with >= 1 core Gleason Score 8 [4+4 or 5+3] included); c) Gleason Score >=9 (=GG 5) in at least 1 systematic or targeted core; d) At least 2 systematic or targeted cores with continuous Gleason Score >=8 (=GG 4), each with > 80 percent (%) involvement
  • Candidate for radical prostatectomy with pelvic lymph node dissection as per the investigator
  • Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
  • Contraceptive use by male participants (and female partners of male participants enrolled in the study who are of childbearing potential or are pregnant) should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies
  • Able to receive androgen deprivation therapy (ADT) for at least 13 months

Exclusion Criteria:

  • Distant metastasis based on conventional imaging (clinical stage M1). Nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion. Diagnosis of distant metastasis (clinical M stage; M0 versus M1a, M1b, M1c) and pelvic nodal disease (clinical N stage; N1 versus N0) will be assessed by central radiological review. Participants are considered eligible only if the central radiological review confirms clinical stage M0
  • (a) Prior treatment with androgen receptor antagonists; (b) Treatment with gonadotropin-releasing hormone analog (GnRHa) prior to informed consent form (ICF) signature
  • History of prior systemic or local therapy for prostate cancer, including pelvic radiation for prostate cancer
  • Use of any investigational agent less than or equals to (<=)4 weeks prior to randomization or any therapeutic procedure for prostate cancer at any time
  • Major surgery <=4 weeks prior to randomization
  • Any of the following within 12 months prior to first dose of study drug: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (example, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias or New York Heart Association Class II to IV heart disease; uncomplicated deep vein thrombosis is not considered exclusionary

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Phase II Study of Neoadjuvant Pembrolizumab Plus Intensive Androgen Axis Blockade Prior to Prostatectomy for High Risk Localized Prostate Cancer


Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03753243

Sponsor: Mark Garzotto, MD

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  • Be willing and able to provide written informed consent/assent for the trial.
  • Capability to understand and comply with the protocol and signed informed consent document.
  • Be ≥ 18 years of age on day of signing informed consent.
  • Have measurable disease based on RECIST 1.1.
  • Histologically confirmed, non-metastatic adenocarcinoma of the prostate
  • Prostatectomy with extended lymph node dissection planned as primary therapy
  • 10 year or longer life expectancy based on other co-morbidities
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  • Any one of the following three high risk features:
  • Gleason grade > 8-10
  • PSA > 20 ng/ml
  • Clinical stage T3a (resectable)
  • No evidence of metastases .
  • No other diagnosis of malignancy (with exception of non-melanoma skin cancer or a malignancy diagnosed ≥5 years ago).
  • Male subjects of childbearing potential must agree to use an adequate method of contraception. Contraception, starting with the first dose of study therapy through the time of surgery. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • Demonstrate adequate organ function, all screening labs should be performed within 30 days of treatment initiation.

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Phase I Study of CART-PSMA-TGFβRDN Cells in Patients With Advanced Castrate Resistant Prostate Cancer


Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03089203

Sponsor: University of Pennsylvania

Phase: Phase 1

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  • 1. Metastatic castrate resistant prostate cancer 2. ≥10% tumor cells expressing PSMA as demonstrated by immunohistochemistry analysis on biopsied tissue. RETIRED WITH PROTOCOL VERSION 15 3. Radiographic evidence of osseous metastatic disease and/or measurable, non-osseous metastatic disease (nodal or visceral) 4. Patients ≥ 18 years of age 5. ECOG performance status of 0
  • 1 6. Adequate organ function, as defined by: 1. Serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 60 cc/min 2. Serum total bilirubin < 1.5x ULN 3. Serum ALT/AST < 2x ULN 7. Adequate hematologic reserve within 4 weeks of eligibility confirmation by physician-investigator as defined by: 1. Hgb > 10 g/dl 2. PLT > 100 k/ul 3. ANC > 1.5 k/ul Note: Subjects must not be transfusion dependent 8. Evidence of progressive castrate resistant prostate adenocarcinoma, as defined by: 1. Castrate levels of testosterone (< 50 ng/ml) with or without the use of androgen-deprivation therapy AND 2. Evidence of one of the following measures of progressive disease in the 12 weeks preceding eligibility confirmation by physician: i. soft tissue progression by RECIST 1.1 criteria ii. osseous disease progression with 2 or more new lesions on bone scan (as per PCWG2 criteria) iii. increase in serum PSA of at least 25% and an absolute increase of 2 ng/ml or more from nadir (as per PCWG2 criteria) 9. Prior therapy with at least one standard initial therapy for the treatment of metastatic castrate resistant prostate cancer (i.e. docetaxel chemotherapy, 17α lyase inhibitor, or second-generation anti-androgen therapy) 10. Provides written informed consent 11. Subjects of reproductive potential must agree to use acceptable birth control methods

Exclusion Criteria:

  1. Treatment with immune checkpoint inhibitors and immunoconjugate therapies, including nivolumab, pembrolizumab, atezolizumab, ipilimumab, and/or durvalumab, within 2 months prior to eligibility confirmation by physician-investigator. Cancer vaccine therapies (such as Sipuleucel-T or PROSTVAC) are allowable as a prior line of therapy. Radium-223 is allowable as a prior line of therapy, provided laboratory complete blood counts meet all inclusion criteria as above, without transfusion support in the preceding 4 weeks.
  2. History of an active non-curative non-prostate primary malignancy within the prior 3 years
  3. Subjects with a rising PSA, but who have never had radiologic evidence of metastatic disease (i.e. 'biochemical recurrence') RETIRED WITH PROTOCOL VERSION 6
  4. Subjects who require the chronic use of systemic corticosteroid therapy. Patients may be on a low dose of steroids (≤10mg equivalent of prednisone).
  5. Subjects who have received > 4 prior therapies for the treatment of castrate resistant prostate cancer (excluding luteinizing hormone-releasing hormone agonists or antagonists, or first generation anti-androgen therapies). Note: Docetaxel or abiraterone/prednisone administered in the castration-sensitive setting will count as a prior line of therapy. RETIRED WITH PROTOCOL V13
  6. Subjects with Class III/IV cardiovascular disability according to the New York Heart Association Classification
  7. Subjects with symptomatic vertebral metastases affecting spinal cord function (as determined by clinical history, physical exam, or MRI imaging)
  8. Active autoimmune disease, including connective tissue disease, uveitis, inflammatory bowel disease, or multiple sclerosis; or a history of severe (as judged by the physician-investigator) autoimmune disease requiring prolonged immunosuppressive therapy
  9. Patients with ongoing or active infection.
  10. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
  11. Active hepatitis B, hepatitis C or HIV infection.
  12. Active medical condition that, in the opinion of the physician-investigator, would substantially increase the risk of uncontrollable CRS or CAR Neurotoxicity.

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A Phase 1/2 Feasibility, Safety, and Activity Study of PSCA-Specific Chimeric Antigen Receptor Engineered T Cells (BPX-601) in Subjects With Previously Treated Advanced Solid Tumors


Condition: Metastatic Castration-resistant Prostate Cancer, Metastatic Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02744287

Sponsor: Bellicum Pharmaceuticals

Phase: Phase 1/Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Metastatic castration-resistant prostate cancer (mCRPC), with progressive disease per PCWG3 criteria during or following the direct prior line of therapy.
  • Measurable disease per RECIST v1.1 at baseline; subjects with mCRPC with bone only metastases must have measurable PSA.
  • Age ≥18 years.
  • Life expectancy > 12 weeks.
  • ECOG 0-1
  • Adequate organ function.

Exclusion Criteria:

  • Prostate cancer with unstable bone lesions or symptomatic/untreated coagulopathy, or history of > Grade 2 hematuria within the previous 6 months.
  • Prior CAR T cell or other genetically-modified T cell therapy. Prior treatment with an immune-based therapy for the treatment of prostate cancer, including cancer vaccine therapies are allowable.
  • Symptomatic, untreated, or actively progressing central nervous system metastases.
  • Impaired cardiac function or clinically significant cardiac disease.
  • Pregnant or breastfeeding.
  • Participant requires chronic, systemic steroid therapy.
  • Severe intercurrent infection.
  • Known HIV positivity.

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Biomarkers of Sulforaphane/Broccoli Sprout Extract in Prostate Cancer


Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03665922

Sponsor: University of Pittsburgh

Eligibility:

  • Age: minimum 18 Years maximum 90 Years
  • Gender: Male

Inclusion Criteria:

  1. Men ≥ 18 years of age scheduled to undergo radical prostatectomy as standard of care for a diagnosis of prostate adenocarcinoma.
  2. Subjects willing to take oral placebo or BroccoMax® pills (4 capsules twice daily after breakfast and dinner) on a daily basis for 4 weeks prior to prostatectomy. Subjects have the ability to swallow BroccoMax® or placebo pills.
  3. Subjects in good health per investigator evaluation with liver enzyme and blood count values within the following ranges: White blood cells ≥ 3,000/mL Total bilirubin ≤ 1.5 x Upper Limits of Normal (ULN) Aspartate Aminotransferase (AST (SGOT))/ Alanine Aminotransferase (ALT (SGPT)) ≤ 2.5 x ULN Blood Urea Nitrogen (BUN) and serum creatinine ≤ 1.5 x ULN
  4. Subjects willing to abstain from dietary sources of glucosinolates and isothiocyanates (see Appendix) for the duration of the study (4 weeks)
  5. Subjects must be fully informed of the investigational nature of this study and must sign a written informed consent in accordance within institutional and regulatory guidelines

Exclusion Criteria:

  1. Subjects ineligible to undergo prostatectomy due to co-morbidities.
  2. Subjects with a second malignancy or any other cancer at least 3 years following definitive treatment with no evidence of disease, except for adequately treated basal cell or squamous cell skin cancer.
  3. Subjects with malabsorption issues or gastrointestinal ailments than can interfere with the ability to adequately absorb SFN.
  4. Subjects with prior or concurrent androgen deprivation therapy with Luteinizing hormone-releasing hormone (LHRH) agonist or antagonists
  5. Subjects taking any other investigational agent, dietary supplement or herbal supplement or participating in clinical studies involving investigational agents
  6. Subjects with clinically significant comorbid diseases including active infection, uncontrolled angina, New York Heart Assoc. (NYHA) class III or IV heart failure, uncontrolled or uncontrollable hypertension, severe diabetes with complications, chronic liver disease.
  7. Subjects with prior history of known intolerance or allergic reactions attributed to cruciferous vegetables or specific fillers used in the placebo.

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Ice-CAP: A Phase I Trial of Ipatasertib in Combination With Atezolizumab in Patients With Advanced Solid Tumours With PI3K Pathway Hyperactivation


Condition: Solid Tumor, Glioblastoma Multiforme, Prostate Cancer Metastatic

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03673787

Sponsor: Institute of Cancer Research, United Kingdom

Phase: Phase 1/Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  1. PART A1: Patients with histologically or cytologically confirmed malignant advanced solid tumours refractory to conventional treatment, or for which no conventional therapy exists or is declined by the patient; PART A2: Patients with advanced glioblastoma with potentially surgically resectable disease. PART B1: Patients with histologically or cytologically confirmed malignant advanced solid tumours, refractory to conventional treatment, or for which no conventional therapy exists or is declined by the patient, with somatic mutations or other aberrations predicted to result in a hyperactivated PI3K-AKT pathway (eg activating mutations in PIK3CA, AKT1, AKT2) or PTEN loss (assessed by immunohistochemistry (IHC) (n=12). PART B2: Patients with histologically or cytologically confirmed malignant castrate refractory prostate cancer, refractory to conventional treatment, or for which no conventional therapy exists or is declined by the patient, with PTEN loss confirmed by immunohistochemistry H-score <30 as established in our local laboratory PART B3: Patients with relapsed histologically confirmed glioblastoma. At least 3 patients will need to have potentially surgically resectable disease.
  2. Part A1: Evaluable disease as assessed by immune-modified RECIST 1.1 (solid tumours). Part A2: Evaluable disease as assessed by Response-assessment in Neuro-Oncology (RANO) criteria for glioblastoma patients. Part B1: Measurable disease as assessed by immune-modified RECIST Part B2: Measurable disease as assessed by immune-modified RECIST 1.1 OR evaluable disease as per Prostate Cancer Working Group 3 (PCWG 3) criteria Part B3: Measurable disease as assessed by RANO
  3. All patients with advanced solid tumours must be willing and able to have fresh paired tissue biopsies for biomarker analysis. All patients with potentially resectable glioblastomas being considered for Part A2 and Part B3 must be willing and able to have surgical resection with fresh tissue samples provided for translational studies.
  4. Life expectancy of at least 12 weeks.
  5. World Health Organisation (WHO) performance status of 0-1
  6. Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week prior to the first dose of either Investigational Medicinal Product (IMP) Haemoglobin (Hb) ≥ 9.0 g/dL Absolute neutrophil count ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x (ULN) unless raised due to tumour in which case up to 5 x ULN is permissible Either: Creatinine OR IF Creatinine > 1.5 times ULN then Calculated creatinine clearance <1.5 times ULN ≥ 50 mL/min (uncorrected value) Coagulation INR < 1.5 APTT <1.5x ULN (except for potentially resectable glioblastoma patients enrolled onto the surgical resection arms where the APTT should be <1.2x ULN Triglycerides ≤ 300 mg/dL Cholesterol ≤ 300 mg/dL 7.18 years or over 8.Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up 9.Female patients with reproductive potential must have a negative serum pregnancy test within 14 days prior to start of trial.

Exclusion Criteria:

  • 1.Radiotherapy, endocrine therapy, immunotherapy or chemotherapy during the previous four weeks (six weeks for nitrosoureas, Mitomycin-C) and four weeks for investigational medicinal products) before treatment, except for hormonal therapy with luteinizing hormone-releasing hormone (LHRH) analogues for medical castration in patients with castrate resistant prostate cancer, which are permitted, and bisphosphonates or RANK ligand antagonists that are permitted for the management of bone metastases. 2.Ongoing Grade 2 or greater toxicities from pre-existing conditions or from previous treatments. Exceptions to this are alopecia. 3.Clinically significant abnormalities of glucose metabolism as defined by any of the following: ◦Diagnosis of diabetes mellitus types I or II (irrespective of management). ◦Glycosylated haemoglobin (HbA1C) ≥7.50% at screening
  • Fasting Plasma Glucose ≥ 8.3mmol/L (150 mg/dL) at screening. Fasting is defined as no caloric intake for at least 8 hours. 4.Ability to become pregnant (or already pregnant or lactating). However, those female patients who have a negative serum pregnancy test before enrolment and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom, have an intra-uterine device and condom, diaphragm with spermicidal gel and condom) from time of consent, during the trial and for six months afterwards are considered eligible. 5.Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception [condom plus spermicide] during the trial and for six months afterwards). Men with pregnant or lactating partners should be advised to use barrier method contraception (for example, condom plus spermicidal gel) to prevent exposure to the foetus or neonate. 6.For patients with solid tumours, known untreated or active central nervous system (CNS) metastases (progressing or requiring corticosteroids for symptomatic control). Patients with a history of treated CNS metastases are eligible, provided they meet all of the following criteria:
  • Evaluable or measurable disease outside the CNS is present.
  • Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the baseline disease assessment
  • Not requiring corticosteroids. 7.Major surgery within four weeks of the first dose of study treatment. 8.History of malabsorption syndrome or other condition that would interfere with enteral absorption. 9.At high medical risk because of non-malignant systemic disease including active uncontrolled infection. 10.Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV). 11.Has a known history of clinically significant liver disease, including viral or other hepatitis or cirrhosis. 12.Has an active autoimmune disease that has required systemic treatment in past 3 months (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patients with a history of inflammatory bowel diseases such as Crohn's disease or ulcerative colitis will be excluded from the study. Patients with Sjogren's syndrome will not be excluded from the study. In addition patients that experienced a Grade 2 or higher immune-related AE's on treatment with immunotherapy will be excluded from the study. Patients with inactive autoimmune disease which has previously required systemic therapy, may be considered on a case-by-case basis after discussion with the sponsor. 13.Has a known history of severe allergic anaphylactic reactions to chimeric, human or humanized antibodies, or fusion proteins. 14.Has a known hypersensitivity to CHO cell products or any component of the atezolizumab formulation. 15.Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the chief Investigator. Stable use (i.e., no change in dose within 1 month prior to Day 1 of Cycle 1 of inhaled corticosteroids is allowed. In the Part B dose expansion only, patients with castrate-resistant prostate cancer who have been on long-term steroids, will be allowed, provided the average total daily dose of steroids for the two weeks prior to commencement of trial is ≤10mg prednisolone/day. Again, in the Part B3 dose expansion only, patients with glioblastoma will be allowed to be enrolled if they had been on a stable dose of steroids ≤3mg Dexamethasone for at least 5 days prior to Day 1 of Cycle 1. 16.Has received a live vaccine within 30 days of planned start of study therapy. Note: The killed virus vaccines used for seasonal influenza vaccines for injection are allowed; however intranasal influenza vaccines (e.g. FluMist®) are live attenuated vaccines and are not allowed. 17.Any of the following cardiac criteria:
  • Mean resting corrected QT interval (QTc) > 470 msec obtained from 3 consecutive electrocardiograms (ECGs) within 5 minutes of each other.
  • Any clinically significant abnormalities in rhythm, conduction or morphology of resting ECG, e.g. complete left bundle branch block, third degree heart block. Controlled atrial fibrillation is allowed.
  • Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association [NYHA Grade 2] 18.Prior bone marrow transplant or have had extensive radiotherapy to greater than 25% of bone marrow within eight weeks. 19.Current malignancies of other types, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for three years or more and are deemed at negligible risk for recurrence, are eligible for the trial. 20.Is a participant or plans to participate in another interventional clinical trial, whilst taking part in this Phase I study of ipatasertib and atezolizumab. Participation in an observational trial would be acceptable. 21.Patients with prior exposure to a PI3K or AKT inhibitors will be excluded from this study. Patients with prior exposure to mTOR inhibitors will be permitted to be enrolled on study. Patients with prior exposure to immunotherapy (either CTLA-4, PD-1/PD-L1 inhibitor/cellular therapy) will be excluded from the dose escalation Part A of the study, but will be permitted to enrol onto the Part B dose expansion as long as they did not experience any ≥Grade 2 immune-adverse event toxicity while on their prior immunotherapy. 22.Is taking or requiring the continued use of any of the prohibited concomitant medications listed in 5.8 Concomitant medication and treatment. 23.Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical trial.

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Phase II Study of Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis


Condition: Prostate

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03047135

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  • 1. Histologic diagnosis of adenocarcinoma of the prostate 2. Prior local therapy with prostatectomy required, with available tissue from prostatectomy specimen to send for genomic and transcriptomic testing. 3. Prior salvage or adjuvant radiation therapy is allowed but not mandated. Radiation therapy must have been completed for at least 6 months. 4. Absolute PSA ≥1 ng/ml. Prior undetectable PSA post-prostatectomy is not required. 5. PSADT ≤6 months, based upon ≥3 consecutive measurements collected in the past 12 months, at least 4 weeks apart 6. No radiographic evidence of metastatic disease by CT scan and bone scan, performed within the prior 4 weeks. 7. Serum testosterone ≥ 150 ng/dl 8. Participants must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
  • Hemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
  • Platelet count ≥ 75 x 109/L
  • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) <2.5 x institutional upper limit of normal. Note: Patients with elevations in bilirubin, AST, or ALT should be thoroughly evaluated for the etiology of this abnormality prior to entry and patients with evidence of viral infection should be excluded.
  • Patients must have creatinine clearance estimated using the Cockcroft
  • Gault equation of ≥51 mL/min: Estimated creatinine clearance = (140-age [years]) x weight (kg) serum creatinine (mg/dL) x 72 9. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 10. Male participants and their partners, who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination [see appendix F for acceptable methods], throughout the period of taking study treatment and for 3 months after last dose of study drug to prevent pregnancy in a partner. 11. For enrichment stage of trial only (if necessary): Confirmation of a suspected/known deleterious mutation in a gene of interest (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, or other DNA repair genes) via CLIA certified testing.

Exclusion Criteria:

  1. Prior ADT in the past 6 months. Prior ADT in context of neoadjuvant/adjuvant primary; prior ADT for biochemical recurrence is allowed, as long as no ADT has been administered in past 6 months and testosterone has recovered (>150 ng/dl). The total duration of prior ADT should not exceed 24 months.
  2. Prior oral anti-androgen (e.g. bicalutamide, nilutamide, enzalutamide, apalutamide), or androgen synthesis inhibitor (e.g. abiraterone, orteronel) in the past 6 months. 5-alpha reductase inhibitor therapy (e.g. finasteride, dutasteride) is allowed, as long as subject has been stable on medication for past 6 months.
  3. Prior treatment with intravenous chemotherapy.
  4. Involvement in the planning and/or conduct of the study
  5. Participation in another clinical study with an investigational product during the last 1 month.
  6. Any previous treatment with PARP inhibitor, including olaparib
  7. Resting ECG with QTc > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
  8. Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
  9. Concomitant use of known strong CYP3A inducers (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for phenobarbital and 3 weeks for other agents.
  10. Myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML.
  11. Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
  12. Poor medical risk due to a serious, uncontrolled medical disorder, non- malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
  13. Unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
  14. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
  15. Known hypersensitivity to olaparib or any of the excipients of the product.
  16. Known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids
  17. Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable, for timing refer to inclusion criteria no.10)

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Phase Ib Trial of Pembrolizumab (MK-3475) With Platinum-Based Chemotherapy in Small Cell/Neuroendocrine Cancers of Urothelium and Prostate


Condition: Bladder Small Cell Neuroendocrine Carcinoma, Castration-Resistant Prostate Carcinoma, Metastatic Bladder Urothelial Carcinoma, Metastatic Urethral Urothelial Carcinoma, Prostate Carcinoma Metastatic in the Bone, Prostate Neuroendocrine Neoplasm, Prostate Small Cell Carcinoma, Stage III Bladder Cancer AJCC v8, Stage III Prostate Cancer AJCC v8, Stage III Urethral Cancer AJCC v8, Stage IV Bladder Cancer AJCC v8, Stage IV Prostate Cancer AJCC v8, Stage IV Urethral Cancer AJCC v8, Stage IVA Bladder Cancer AJCC v8, Stage IVB Bladder Cancer AJCC v8, Ureter Small Cell Carcinoma, Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03582475

Sponsor: Jonsson Comprehensive Cancer Center

Phase: Phase 1

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Histologically confirmed diagnosis of locally advanced or metastatic 1) naive small cell cancer of the bladder, urethra, or upper urinary tract, or 2) primary small cell or neuroendocrine prostate cancer will be enrolled in this study.
  • Histological diagnosis of pure or mixed small cell or neuroendocrine cancer by a genitourinary pathologist is sufficient and confirmatory immunohistochemistry is not required.
  • Cohort 1 will include subjects with no prior systemic chemotherapy for locally advanced or metastatic urothelial carcinoma, with the following exception(s):
  • Platinum-based chemotherapy with recurrence > 12 months from completion of therapy is permitted.
  • Cohort 2 will include subjects with no prior systemic chemotherapy for primary small cell prostate cancer, with the following exception(s):
  • Platinum-based chemotherapy with recurrence > 12 months from completion of therapy is permitted.
  • Cohort 2 will include subjects with prior treatments for metastatic castration-resistant prostate cancer (mCRPC) including:
  • Prior chemotherapy with 2 other agents is allowed if > 6 months elapsed from last dose (if docetaxel chemotherapy is used more than once for hormone-sensitive and for mCRPC it will be considered 1 therapy).
  • Ongoing androgen deprivation therapy with up to 2 second-generation hormonal manipulations (e.g. including but not limited to abiraterone acetate and/or enzalutamide).
  • Ongoing treatment with for bone metastasis (e.g. denosumab or zoledronic acid) is permitted.
  • Prior immunotherapy with sipuleucel-T is allowed if completed > 4 weeks prior to trial enrollment.
  • A male participant must agree to use contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab or 180 days after chemotherapy and refrain from donating sperm during this period.
  • A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
  • Not a woman of childbearing potential (WOCBP) or
  • A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of pembrolizumab or 180 days after chemotherapy.
  • The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
  • Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  • Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated within 6 months of screening. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. In addition, the availability of fresh frozen tissue is encouraged. Newly obtained biopsies are preferred to archival tissue.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of allocation.
  • Absolute neutrophil count (ANC) >= 1500/uL within 10 days prior to the start of study treatment.
  • Platelets >= 100 000/uL within 10 days prior to the start of study treatment.
  • Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L within 10 days prior to the start of study treatment.
  • Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
  • Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 30 mL/min for participant with creatinine levels >1.5 x institutional ULN within 10 days prior to the start of study treatment.
  • Creatinine clearance (CrCl) should be calculated per institutional standard.
  • Total bilirubin =< 1.5 ?ULN or direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 ? ULN within 10 days prior to the start of study treatment.
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 ? ULN (=< 5 ? ULN for participants with liver metastases) within 10 days prior to the start of study treatment.
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 ? ULN unless participant is receiving anticoagulant therapy as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants within 10 days prior to the start of study treatment.

Exclusion Criteria:

  • Has disease suitable for local treatment with curative intent.
  • A WOCBP who has a positive urine pregnancy test within 72 hours prior to receiving the first dose of trial medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137).
  • Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to first dose of trial treatment.
  • Note: Participants must have recovered from all AEs due to previous therapies to =< grade 1 or baseline. Participants with =< grade 2 neuropathy may be eligible.
  • Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
  • Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=< 2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
  • Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette?Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist) are live attenuated vaccines and are not allowed.
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
  • Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
  • Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
  • For Cohort 1, a history of prostate cancer that was identified incidentally following cystoprostatectomy for bladder cancer is acceptable provided that the PSA is < 0.2.
  • Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
  • Has severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a known history of human immunodeficiency virus (HIV).
  • Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid [RNA] [qualitative] is detected) infection. Note: no testing for hepatitis B and hepatitis C is required unless mandated by local health authority.
  • Has a known history of active TB (bacillus tuberculosis).
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject?s participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.

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A Phase II Randomized Controlled Trial of Stereotactic Ablative Body Radiotherapy (SAbR) With or Without Neurovascular Sparing for Erectile Function Preservation in Localized Prostate Cancer


Condition: Prostate Cancer Adenocarcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03525262

Sponsor: University of Texas Southwestern Medical Center

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  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:
  15. Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
  16. Myocardial infarction within the last 6 months
  17. Acute bacterial or fungal infection requiring intravenous antibiotics at time of registration
  18. Patients with active inflammatory colitis (including Crohn's Disease and ulcerative colitis) currently requiring systemic steroids and/or systemic immunosuppression are not eligible.
  19. Subjects with a known allergy to polyethylene glycol hydrogel (rectal spacer material) or contraindication to spacer products (SpaceOAR).
  20. Subjects with uncontrolled coagulation disorder which cannot be controlled with anticoagulants.
  21. 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.
  22. 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.
  23. Men who have clinically significant penile malformation (i.e. Peyronie's disease) or history of penile implantation are excluded.
  24. 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.

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The Role of Androgen Deprivation Therapy In Cardiovascular Disease - A Longitudinal Prostate Cancer Study (RADICAL PC1) & A RAndomizeD Intervention for Cardiovascular and Lifestyle Risk Factors in Prostate Cancer Patients (RADICAL PC2)


Condition: Prostate Cancer, Cardiovascular Disease

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03127631

Sponsor: McMaster University

Eligibility:

  • Age: minimum 45 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  • 1. A man with a diagnosis of prostate cancer that is either:
  • new (i.e. the diagnosis was made within 1 year of the enrolment visit) or
  • treated with Androgen Deprivation Therapy for the first time within 6 months prior to the enrolment visit, or
  • to be treated with Androgen Deprivation Therapy for the first time within 1 month after the enrolment visit

Exclusion Criteria:

  1. Patients will be excluded if they fulfill any of the following:
  2. are unwilling to provide consent or
  3. are <45 years of age, or
  4. prostate cancer was found incidentally following cystectomy for bladder cancer
  5. Patients will be eligible for RADICAL PC1, but will not be eligible for RADICAL PC2 if they:
  6. see a cardiologist every year, or
  7. both take a statin and have systolic blood pressure ≤130mmHg

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Radiometabolic Therapy (RMT) With 177Lu PSMA 617 in Advanced Castration Resistant Prostate Cancer (CRPC): Efficacy and Toxicity Evaluation


Condition: Metastatic Castration Resistant Prostate Cancer, 68Ga-PSMA PET/CT Positive

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03454750

Sponsor: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  1. Male, Age > 18 years.
  2. Patients must have histologically or cytologically confirmation of advanced prostate cancer castration resistant defined according to PCWG3 criteria
  3. Measurable disease according to RECIST 1.
  4. criteria; also patients with bone lesions only could be enrolled
  5. Patients with documented disease will be admitted to therapeutic phase only if the diagnostic PET/CT 68Ga-PSMA images demonstrate a significant uptake (tumor to background ratio >2.5) at metastatic tumour site (or in the primary when present, or both)
  6. Patients with documented radiological progression (in soft tissue and / or bone) and / or biochemical progression (sequence of 3 PSA rising values from a screening PSA value ≥ 2 ng / ml) according to PCWG3 in pre-study period, refractory or unfit to conventional standard treatments (hormonal or chemotherapeutic treatment such as abiraterone, enzalutamide and docetaxel)
  7. Concomitant LHRH analogs assumption is allowed
  8. Life expectancy greater than 6 months.
  9. ECOG performance status <2
  10. Adequate haematological, liver and renal function: haemoglobin >= 9 g/dL, absolute neutrophil count (ANC) >= 1.5 x 109 /L, platelets >= 100 x 109 /L, bilirubin ≤1.5 X upper normal limit (UNL), alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) <2.5 X UNL (< 5 X UNL in presence of liver metastases, creatinine < 2 mg/dL).
  11. Participant is willing and able to give informed consent for participation in the study
  12. Other known malignant neoplastic diseases in the patient's medical history with a disease-free interval of less than 3 years (except for previously treated basal cell carcinoma).

Exclusion Criteria:

  1. Patients treated with chemotherapy and 223Ra radiotherapy within 4 weeks and treated within 2 weeks with palliative radiotherapy.
  2. All acute toxic effects of any prior therapy (including surgery, radiation therapy, chemotherapy) must have resolved to a grade ≤ 1 according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE)
  3. ECOG performance status >2
  4. Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
  5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  6. Assessed bone marrow invasion > 50%

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Circulating Tumor Cell Analysis in Patients With Localized Prostate Cancer Undergoing Prostatectomy


Condition: Prostate Cancer

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT01961713

Sponsor: Massachusetts General Hospital

Phase:

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  • Male
  • 18 years of age or older
  • Pathologically confirmed diagnosis of prostate adenocarcinoma
  • Non-metastatic prostate cancer
  • Planned radical prostatectomy at Massachusetts General Hospital

Exclusion Criteria:

  • Patients must not have received prior radiation therapy, hormone therapy, or other medical therapy for prostate cancer prior to prostatectomy. Post-prostatectomy therapy at the discretion of the patient's treating physician(s) is allowed.
  • Patients must not have metastatic prostate cancer
  • No prior or current diagnosis of epithelial malignancy, except for skin cancer (squamous cell carcinoma or basal cell carcinoma)

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Evaluation of the TULSA-PRO MRI-Guided Transurethral Ultrasound Prostate Ablation Device in Patients With Localized Prostate Cancer: a Prospective, Single-Arm, Pivotal Clinical Study


Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02766543

Sponsor: Profound Medical Inc.

Eligibility:

  • Age: minimum 45 Years maximum 80 Years
  • Gender: Male

Inclusion Criteria:

  1. Male, age 45 to 80 years
  2. Biopsy-confirmed adenocarcinoma of the prostate. Biopsy (minimum 10 cores) obtained ≥ 6 weeks and ≤ 6 months before treatment (or at the discretion of PI and approval by the Sponsor).
  3. Clinical stage ≤ T2b 4.1 Gleason score ≤ 3 + 4 (Part I only) 4.2 Gleason score 3+4 (Part II only) *now recruiting
  4. PSA ≤ 15 ng/ml
  5. Eligible for MRI [Form GCP-10131]
  6. Eligible for general anesthesia (ASA category ≤ 3)
  7. Prostate volume ≤ 90 cc, on Baseline MRI
  8. Prostate size ≤ 5.0 cm in sagittal length, and ≤ 6.0 cm in axial diameter, on Baseline MRI
  9. Life expectancy ≥ 10 years
  10. No calcifications in the planned ultrasound beam path, or at the discretion of the investigator with approval from the Sponsor. Exclusion Criteria:
  11. Evidence (including Baseline MRI and bone scan) of extracapsular extension, sphincter involvement, seminal vesicle invasion, lymph node invasion or metastases
  12. Suspected tumour on Baseline MRI within 3 mm of the prostatic urethra, or in the prostate apex within 3 mm from the sphincter plane
  13. Prior definitive treatment of prostate cancer
  14. Prior transurethral resection of the prostate (TURP)
  15. Use of 5-alpha reductase inhibitors (5-ARIs) or hormone therapy within 3 months prior to the baseline visit. Baseline PSA must be established after a minimum of 3 months following 5-ARIs discontinuation. Additionally, use of 5-ARIs is not permitted following treatment during the study follow-up period.
  16. Prostate calcifications > 1 cm in largest diameter, on Baseline Ultrasound
  17. Cysts > 1 cm in largest diameter, on Baseline MRI
  18. Bleeding disorder (INR > ULN and PTT > ULN)
  19. Abnormal coagulation and current anticoagulant therapy. Patients whose anticoagulation therapy can be temporarily reversed within 7 days prior to treatment are eligible. Platelet inhibitors (ie: ASA) and heparin are not

Exclusion Criteria:

  1. Evidence (including Baseline MRI and bone scan) of extracapsular extension, sphincter involvement, seminal vesicle invasion, lymph node invasion or metastases
  2. Suspected tumour on Baseline MRI within 3 mm of the prostatic urethra, or in the prostate apex within 3 mm from the sphincter plane
  3. Prior definitive treatment of prostate cancer
  4. Prior transurethral resection of the prostate (TURP)
  5. Use of 5-alpha reductase inhibitors (5-ARIs) or hormone therapy within 3 months prior to the baseline visit. Baseline PSA must be established after a minimum of 3 months following 5-ARIs discontinuation. Additionally, use of 5-ARIs is not permitted following treatment during the study follow-up period.
  6. Prostate calcifications > 1 cm in largest diameter, on Baseline Ultrasound
  7. Cysts > 1 cm in largest diameter, on Baseline MRI
  8. Bleeding disorder (INR > ULN and PTT > ULN)
  9. Abnormal coagulation and current anticoagulant therapy. Patients whose anticoagulation therapy can be temporarily reversed within 7 days prior to treatment are eligible. Platelet inhibitors (ie: ASA) and heparin are not exclusion criteria.
  10. Acute unresolved Urinary Tract Infection (UTI)
  11. Interest in future fertility
  12. History of any other malignancy other than skin cancer, or low grade bladder cancer which has been completely resected, within the previous 2 years. Patients that have had curative treatment of a previous malignancy and no recurrence of that malignancy within the past 2 years will be allowed.
  13. Patients with peripheral arterial disease with intermittent claudication or Leriches Syndrome
  14. Patients with diabetes who have evidence of complications from their diabetes, such as end organ sequelae of diabetes or Hemoglobin A1c > 7%.
  15. History of any major rectal or pelvic surgery or radiotherapy
  16. History of ulcerative colitis or other chronic inflammatory conditions affecting rectum (includes rectal fistula, anal stenosis)
  17. Documented clinical prostatitis requiring therapy within 6 months prior to Treatment
  18. History of urethral and bladder outlet disorders, including urethral stricture disease, urethral diverticulae, bladder neck contracture, urethral fistulae, urethral stenting, urethral sling, urethroplasty or chronic indwelling urethral catheter
  19. Patients with artificial urinary sphincter or any penile implant
  20. Severe neurogenic bladder
  21. Untreated bladder stones
  22. History of acute urinary retention within the last 12 months
  23. Active untreated gross hematuria for any cause
  24. Post Void Residual (PVR) bladder volume > 250 mL
  25. Obstructing median lobe enlarged out of proportion to the rest of the prostate and protruding significantly into the bladder, sometimes referred to as "ball valve" median lobe, determined on Baseline MRI
  26. Any prostate related investigational therapy within 6 months of Visit 1
  27. History of Parkinson's disease or multiple sclerosis
  28. History of drug abuse
  29. Known infectious disease including HIV positivity or AIDS-related illness, HBV and HCV
  30. Current unilateral or bilateral hydronephrosis
  31. Allergy or contraindications to administration of the GI anti-spasmodic drug:
  32. Patients in the USA: Glucagon
  33. Patients in Canada and Europe: Buscopan (Hyoscine)
  34. Contraindications to administration of gadolinium-based MRI contrast agent (e.g. Magnevist), such as chronic, severe kidney disease, acute kidney injury, history of Sickle Cell Disease, history of anemia, or intolerance/allergy to the contrast agent
  35. Other severe, acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results

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Prospective Evaluation of CyberKnife Stereotactic Body Radiotherapy for Localized Prostate Cancer: Risk Stratified Monotherapy Versus Boost


Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02016248

Sponsor: MemorialCare Health System

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  1. Histologically proven prostate adenocarcinoma
  2. Biopsy within 12 months of date of registration
  3. Clinical Stage I-IV, MX-M0 (AJCC 6th Edition) M-stage determined by physical exam, CT, MRI, or Bone Scan. Bone scan not required for Monotherapy Risk Group patients unless clinical findings suggest possible osseous metastases. Bone Scan and contrast CT of the abdomen should be done patients in the Boost Risk Group patients.
  4. Prostate volume: ≤ 100 cc (recommended not required) Determined using: volume = π/6 x length x height x width Measurement from CT or ultrasound ≤90 days prior to registration.
  5. ECOG performance status 0-1
  6. No prior prostatectomy or cryotherapy of the prostate
  7. No prior radiotherapy to the prostate or lower pelvis
  8. No implanted hardware or other material that would prohibit appropriate treatment planning or treatment delivery, in the investigator's opinion.
  9. Completion of patient questionnaires
  10. Consent signed

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Cognitive Effects of Androgen Receptor (AR) Directed Therapies for Advanced Prostate Cancer


Condition: Castration-Resistant Prostatic Cancer, Metastatic Prostate Carcinoma, Recurrent Prostate Carcinoma, Stage IV Prostate Cancer, Hormone-Refractory Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03016741

Sponsor: Northwestern University

Phase: Phase 4

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  • Have diagnosis of prostate cancer and have received treatment with GnRH agonist or antagonist therapy for at least 1 month prior to enrollment.
  • Willing and able to complete survey questionnaires in English without assistance through the duration of the study. This stipulation is in place because not all of the proposed quality of life or cognitive tests are available or validated in other languages.
  • Age ≥ 18 years.
  • Ability to understand and the willingness to sign a written informed consent document written in English that is approved by an institutional review board.
  • Have either newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) or castration-resistant metastatic prostate cancer (mCRPC) and eligible to undergo treatment with abiraterone acetate (mHSPC or mCRPC) or enzalutamide (mCRPC)
  • Patients may have received the following prior AR directed therapy prior to enrollment: bicalutamide, ketoconazole. Prior to enrollment, patients may have received treatment with abiraterone acetate or enzalutamide for no more than 14 days before completing baseline studies.
  • Patients may have received chemotherapy for hormone-sensitive metastatic prostate cancer only, but it must not have lasted for more than 6 months. At least 12 months must have elapsed since completion of chemotherapy.
  • Patients may have received prior definitive radiation therapy or surgery. At least 60 days must have elapsed since completion of definitive radiation therapy or surgery and patient must have only grade 2 or less adverse effects at the time of registration. Enrollment during palliative radiation of ≤ 10 days, or radiation of ≤ 10 days during the duration of the study is allowed.
  • Patients must be able to take oral medication.

Exclusion Criteria:

  • Prior treatment with enzalutamide or abiraterone acetate for > 14 days prior to enrollment and completion of baseline tests.
  • Receipt of chemotherapy for prostate or other cancer within the past 12 months with residual cognitive deficits, or receipt of chemotherapy for mCRPC. Patients/physicians planning treatment with chemotherapy during the 12 month period of the investigation are also ineligible.
  • History of cognitive impairment or dysfunction, including a history of dementia, Alzheimer's disease, stroke with residual cognitive deficits, cognitive dysfunction related to alcohol or substance abuse, or cognitive dysfunction related to prior treatment for any cancer.
  • Patients with a seizure history, history of recurrent falls, or known brain metastases are excluded from this clinical trial because of their poor prognosis and because of their heightened risk of seizure or progressive cognitive and/or neurologic dysfunction that would confound the evaluation.
  • Uncontrolled intercurrent illness including, but not limited to, uncontrolled diabetes, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III and IV heart failure), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations/substance abuse that would limit compliance with study requirements.
  • Patients with a "currently active" second malignancy other than non-melanoma skin cancers are not eligible. Patients are not considered to have a "currently active" malignancy if they have completed all therapy and are now considered without evidence of disease for 1 year. Patients with cognitive dysfunction related to treatment of another malignancy, including a history of "chemo-brain", are ineligible.
  • Patients taking psychotropic medications or illicit drugs that may alter cognition, concentration, or behavior. Appropriate treatment by a licensed provider with medications for depression or anxiety, including but not limited to SSRIs, SNRIs, and standard dose benzodiazepines at a stable dose, is permitted

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A Randomized Multicenter Phase III Trial Comparing Enzalutamide vs. a Combination of Ra223 and Enzalutamide in Asymptomatic or Mildly Symptomatic Castration Resistant Prostate Cancer Patients Metastatic to Bone.


Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02194842

Sponsor: European Organisation for Research and Treatment of Cancer - EORTC

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  • Histologically confirmed diagnosis of prostate adenocarcinoma
  • Asymptomatic or mildly symptomatic (defined as short form question #3 in Brief Pain Inventory worst pain must be < 4, see Appendix E)
  • Metastatic to bone with ≥ 4 bone metastases (ambiguous areas of increased uptake on 99mTc Bone Scan (BS) should be confirmed by CT or MRI) with or without additional lymph node metastases. Patients with visceral metastases are not allowed. Patients with multifocal bone lesions are allowed; while patients with diffuse confluent bone lesions (superscan) are not allowed in the trial.
  • Note: Patients must start treatment with a bone protecting agent (at doses used to reduce the incidence of skeletal related events) ideally before or at the time of randomization, if patient is not already on one. A minimum of two doses is recommended before the first administration of Ra223 in the experimental arm. The first administration of Ra223 should be scheduled at least 6 weeks after the first administration of bone protecting agent.
  • Note: For French sites only, patients must not have undergone a PET/CT scan for restaging prostate cancer using radiopharmaceuticals such as 18F-FDG, 18F-fluoride, 18F-Fluorocholine or a PSMA (prostate-specific membrane antigen) ligand or any other tracer.
  • Progressive CRPC according to Prostate Cancer Working Group 3 (PCWG3) (Ref. 22) i.e. either:
  • For patients who manifest disease progression solely as a rising PSA level, PCWG3 criteria require documentation of a sequence of rising PSA values at a minimum of 1-week intervals with the last value > 2 ng/mL
  • For patients with disease progression manifest in the bone, irrespective of progression by rising PSA, PCWG3 guidelines require appearance of 2 or more new lesions. Ambiguous results should be confirmed by other imaging modalities than bone scan (e.g.: CT-scan or MRI)
  • For patients with disease progression manifest at nodal sites, irrespective of progression by rising PSA, PCWG3 requires progression according to RECIST 1.1
  • Ongoing androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) agonist or antagonist or bilateral orchiectomy
  • No known central nervous system metastases or leptomeningeal tumor spread.
  • Patients must be at least 18 years old
  • WHO Performance status 0-1(see Appendix C)
  • Charlson score ≤ 3 (see Appendix G)
  • T-score ≥ -2.5 on a DXA scan done in the past 12 months Note: For French sites only, DXA scan done within 6 weeks of randomization
  • Castrate serum levels of testosterone < 50 ng/dL
  • Biochemistry and hematology:
  • Adequate bone marrow function (absolute neutrophil count (ANC) ≥ 1.5 109/L; platelets ≥100 109/L, and hemoglobin ≥ 10.0 g/dL)
  • Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN), except for patient with Gilbert's disease where ≤ 5.0 × ULN applies
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
  • Creatinine ≤ 1.5 x ULN
  • Albumin > 25 g/L
  • Normal cardiac function according to local standard by 12-lead ECG (complete, standardized 12-lead recording)
  • No significant cardiovascular disease including:
  • Myocardial infarction within 6 months prior to screening
  • Uncontrolled angina within 3 months prior to screening
  • Congestive heart failure New York Heart Association (NYHA) class III or IV, or patients with history of congestive heart failure NYHA class III or IV in the past, unless a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within 3 months results in a left ventricular ejection fraction that is ≥ 45%
  • History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)
  • History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
  • Uncontrolled hypertension as indicated by a resting systolic blood pressure > 140 millimeters of mercury (mm Hg) or diastolic blood pressure > 90 mm Hg at screening. Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to randomization. Blood pressure must be re-assessed on two occasions that are separated by a minimum of 1 hour. The mean SBP / DBP values from all blood pressure assessment timepoints must be ≤140/90 mm Hg in order for a patient to be eligible for the study.
  • Hypotension as indicated by systolic blood pressure < 86 mm Hg at screening
  • Bradycardia as indicated by a heart rate of < 45 beats per minute on the screening ECG and on physical examination
  • Uncontrolled hyperglycemia as indicated by a fasting glucose ≥ 7 mmol/L
  • Able to swallow the study drug and comply with study requirements
  • Prior or concomitant therapy
  • Prior docetaxel is permitted if given in the castration sensitive state and if it was started within 4 months of ADT initiation Note: patients having received docetaxel for CRPC are excluded.
  • Prior use of abiraterone is permitted if the patient had a response or stable disease on abiraterone for a minimum of 1 year for metastatic castration sensitive prostate cancer
  • Note: patients having received abiraterone for CRPC are excluded. Prior treatment with abiraterone is allowed if it was stopped at least 4 weeks prior to randomization
  • No prior treatment with enzalutamide, apalutamide, darolutamide or Ra223
  • No concomitant treatment with Cyp17 inhibitors (abiraterone, orteronel) and ketoconazole
  • Previous treatment with bicalutamide or flutamide is allowed if it was stopped at least 48 hours prior to randomization
  • Corticosteroids are allowed only at a dose ≤ 10 mg of prednisone (or equivalent) no matter the indication
  • No prior hemibody external radiotherapy. Patients who received other types of prior external radiotherapy are allowed provided that the bone marrow function is assessed and meets the protocol requirements for hemoglobin, absolute neutrophil count and platelets
  • No prior therapy with other radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188)
  • No involvement in another therapeutic trial involving an experimental drug
  • No anticancer therapy (except ADT) or treatment with another investigational agent within the last 4 weeks prior to randomization
  • No known hypersensitivity to compounds related to enzalutamide or Ra223 (refer to Investigator's brochures)
  • No prior history of malignancies other than prostate adenocarcinoma (except patients with basal cell, squamous cell carcinoma of the skin, in-situ carcinoma or low-grade superficial bladder cancer), or the patient has been free of malignancy for a period of 3 years prior to randomization date
  • No history of seizure, including any febrile seizure, loss of consciousness, or transient ischemic attack within 12 months of randomization, OR any condition that may pre-dispose to seizure (e.g., prior stroke, brain arterio-venous malformation, head trauma with loss of consciousness requiring hospitalization)
  • Drugs known to lower the seizure threshold or prolong QT interval are not permitted (refer to section 5.9.3.2)
  • No major surgery within 4 weeks prior to treatment
  • No drug or alcohol abuse
  • No other serious illness or medical condition, such as but not limited to:
  • Any infection ≥ Grade 2 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4
  • No gastrointestinal disorder affecting absorption (e.g., gastrectomy or active peptic ulcer disease)
  • Crohn's disease or ulcerative colitis
  • Osteonecrosis of the jaw
  • Any bone disease with an osteoblastic activity
  • Bone marrow dysplasia
  • Fecal incontinence
  • Life-threatening illness unrelated to cancer
  • No condition which, in the investigator's opinion, makes the patient unsuitable for trial participation
  • Participants who have pregnant partners must use a condom and those with partners of childbearing potential must use a condom and another adequate birth control measure if engaging in sexual activities during the study treatment period and for at least 3 months after last dose of enzalutamide and 6 months after the last dose of Ra223. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly
  • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
  • Before patient randomization, written informed consent must be given according to ICH/GCP, and national/local regulations
  • For participation in translational research, specific consent must be given. Important note: All

Eligibility Criteria:

  1. must be adhered to, in case of deviation discussion with EORTC Headquarters and study coordinator is mandatory

Exclusion Criteria:

  • No known history of central nervous system metastases or leptomeningeal tumor spread.
  • No significant cardiovascular disease including: 1. Myocardial infarction within 6 months prior to screening 2. Uncontrolled angina within 3 months prior to screening 3. Congestive heart failure New York Heart Association (NYHA) class III or IV, or patients with history of congestive heart failure NYHA class III or IV in the past, unless a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within 3 months results in a left ventricular ejection fraction that is ≥ 45% 4. History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes) 5. History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place 6. Uncontrolled hypertension as indicated by a resting systolic blood pressure > 170 mm Hg or diastolic blood pressure > 105 mm Hg at screening 7. Hypotension as indicated by systolic blood pressure < 86 millimeters of mercury (mm Hg) at screening 8. Bradycardia as indicated by a heart rate of < 45 beats per minute on the screening ECG and on physical examination
  • patients having received docetaxel for CRPC are excluded.
  • No prior treatment with enzalutamide or Ra223
  • No prior and concomitant treatment with Cyp17 inhibitors (abiraterone, orteronel) and ketoconazole
  • No prior hemibody external radiotherapy. Patients who received other types of prior external radiotherapy are allowed provided that the bone marrow function is assessed and meets the protocol requirements for hemoglobin, absolute neutrophil count and platelets
  • No prior therapy with other radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188)
  • No involvement in another therapeutic trial involving an experimental drug
  • No anticancer therapy or treatment with another investigational agent within the last 4 weeks prior to randomization
  • No known hypersensitivity to compounds related to enzalutamide or Ra223
  • No prior history of malignancies other than prostate adenocarcinoma (except patients with basal cell, squamous cell carcinoma of the skin, in-situ carcinoma or low-grade superficial bladder cancer), or the patient has been free of malignancy for a period of 3 years prior to randomization date
  • No history of seizure, including any febrile seizure, loss of consciousness, or transient ischemic attack within 12 months of enrollment (registration date), or any condition that may pre-dispose to seizure (e.g., prior stroke, brain arterio-venous malformation, head trauma with loss of consciousness requiring hospitalization)
  • No major surgery within 4 weeks prior to treatment
  • No intake of narcotic analgesia for bone pain
  • No drug or alcohol abuse
  • No other serious illness or medical condition, such as but not limited to: 1. Any infection ≥ Grade 2 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4 2. No gastrointestinal disorder affecting absorption (e.g., gastrectomy or active peptic ulcer disease) 3. Crohn's disease or ulcerative colitis 4. Bone marrow dysplasia 5. Fecal incontinence 6. Life-threatening illness unrelated to cancer
  • No condition which, in the investigator's opinion, makes the patient unsuitable for trial participation

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International Registry for Men With Advanced Prostate Cancer (IRONMAN)


Condition: Prostate Cancer

Study Type: Observational [Patient Registry]

Clinical Trials Identifier NCT 8-digits: NCT03151629

Sponsor: Prostate Cancer Clinical Trials Consortium

Phase:

Eligibility:

  • Age: minimum 21 Years maximum N/A
  • Gender: Male

Criteria: • Willing and able to provide written informed consent and privacy authorization for the release of personal health information. NOTE: Privacy authorization may be either included in the informed consent or obtained separately. - Males 21 years of age and above - Histological or cytological confirmed prostate adenocarcinoma from TRUS biopsy, radical prostatectomy or TURP Or Documented histopathology or cytopathology of prostate adenocarcinoma from a biopsy of a metastatic site Or Metastatic disease typical of prostate cancer (i.e., involving bone or pelvic lymph nodes or para-aortic lymph nodes) AND a serum concentration of PSA >20ng/mL - No previous diagnosis of a second, non-prostate malignancy that requires additional systemic therapy except cancer in situ of bladder and basal cell cancer of skin

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Phase IIIb Randomized Trial Comparing Irradiation Plus Long Term Adjuvant Androgen Deprivation With GnRH Antagonist Versus GnRH Agonist Plus Flare Protection in Patients With Very High Risk Localized or Locally Advanced Prostate Cancer. A Joint Study of the EORTC ROG and GUCG


Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02799706

Sponsor: European Organisation for Research and Treatment of Cancer - EORTC

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum 80 Years
  • Gender: Male

Inclusion Criteria:

  • Histologically confirmed diagnosis of prostate adenocarcinoma
  • PSA ≥ 10 ng/ml and two of the following 4 criteria:
  • PSA ≥ 20 ng/ml,
  • Gleason sum ≥ 8,
  • cN1 (regional LN with a short axis length >10mm by CT scan or MRI) or pathologically confirmed lymph nodes (pN1),
  • cT3-T4 (by MRI or core biopsy) (i.e. If PSA≥ 20 ng/ml then only one of the other 3 risk factors is needed)
  • M0 by standard imaging work-up (see chapter 6.1.1.1)
  • Testosterone ≥ 200 ng/dl
  • Adequate renal function: calculated creatinine clearance ≥ 50 mL/min (Appendix D) Magnesium and potassium within normal limits of the institution or corrected to within normal limits prior to the first dose of treatment.
  • Patients with prolonged QT-intervals due to prescribed Class IA (quinidine, procainamide) or Class III (amiodarone, sotalol) antiarrhythmic medication must be carefully evaluated for GnRH-agonist or GnRH antagonist use, because these drugs may prolong the QT-interval.
  • WHO Performance status 0-1
  • Age ≥ 18 and ≤ 80 years
  • Participants who have partners of childbearing potential must use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 3 months after last dose of study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly
  • Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclusion Criteria:

  • Previous use of androgen deprivation therapy (ADT), antiandrogens. 5-alpha reductase inhibitors are allowed if interrupted for more than 6 months prior to entering the study
  • History of severe untreated asthma, anaphylactic reactions or severe urticaria and/or angioedema.
  • Hypersensitivity towards the investigational drug
  • The following biological parameters :AST, ALT, total bilirubin, prothrombin time, serum albumin above upper level of normal range No severe hepatic impairment (Child Pugh C)
  • History of gastro-intestinal disorders (medical disorder or extensive surgery) that may interfere with the absorption of the protocol treatment.
  • History of pituitary or adrenal dysfunction
  • Uncontrolled diabetes mellitus
  • History of ulcerative colitis, Crohn's Disease, ataxia, telangiectasia, systemic lupus erythematous, or Fanconi anemia.
  • Clinically significant heart disease as evidence myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) class III or IV heart disease or cardiac ejection fraction measurement of < 50 % at baseline
  • Coronary revascularization (PCI or multivessel CABG), carotid artery or iliofemoral artery revascularization (percutaneous or surgical procedure) within the last 30 days prior to entering the trial
  • Certain risk factors for abnormal heart rhythms/QT prolongation: torsade de pointes ventricular arrhythmias (e.g, heart failure, hypokalemia, or a family history of a long QT syndrome), a QT or corrected QT (QTc) interval >450 ms at baseline, or intake of medications that prolong the QT/QTc interval
  • Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg); patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment.
  • Prior history of malignancies other than prostate adenocarcinoma (except patients with basal cell, squamous cell carcinoma of the skin), or the patient has been free of malignancy for a period of 3 years prior to first dose of study drug(s). Prior history of bladder cancer excludes the patient.
  • Prior radical prostatectomy (TURP or suprapubic adenomectomy for benign prostatic hyperplasia is allowed)
  • Prior brachytherapy or other radiotherapy that would result in an overlap of radiotherapy fields
  • Any contraindication to external beam radiotherapy
  • Patients with significantly altered mental status prohibiting the understanding of the study or with psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule or any condition which, in the opinion of the investigator, would preclude participation in this trial

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