Prostate Cancer

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A Phase III Double-Blind, Randomised, Placebo-Controlled Study Assessing the Efficacy and Safety of Capivasertib+Abiraterone Versus Placebo+Abiraterone as Treatment for Patients With DeNovo Metastatic Hormone-Sensitive Prostate Cancer Characterised by PTEN Deficiency.


Condition: Hormone-Sensitive Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04493853

Sponsor: AstraZeneca

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum 130 Years
  • Gender: Male

Inclusion Criteria:

  • Asymptomatic or mildly symptomatic, histologically-confirmed de novo metastatic hormone-sensitive prostate adenocarcinoma without small-cell tumours
  • Provide a FFPE tissue block (preferred) or slides. Tissue from bone metastases is not acceptable
  • A valid PTEN IHC result indicating PTEN deficiency (centralized testing)
  • Metastatic disease documented prior to randomisation by clear evidence of ≥ 1 bone lesion and/or ≥ 1 soft tissue lesion accurately assessed at baseline and suitable for repeated assessment with CT and/or MRI. PSMA PET identification only will not be eligible
  • Candidate for abiraterone and steroid therapy
  • Ongoing ADT with GnRH analogue, or LHRH agonists or antagonist, or bilateral orchiectomy (regardless of method) is from 0 days to a max. of 3 months prior to randomisation
  • Eastern Cooperative Oncology Group (ECOG)/WHO performance status 0 to 1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks
  • Able and willing to swallow and retain oral medication
  • 7-day Brief Pain Inventory-Short Form (BPI-SF) and Brief Fatigue Inventory(BFI) questionnaires and the analgesic diary during screening completed
  • Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria:

  • Radiotherapy with a wide field of radiation within 4 weeks before the start of study treatment (capivasertib/placebo)
  • Major surgery (excluding placement of vascular access, transurethral resection of prostate, bilateral orchiectomy, or internal stents) within 4 weeks of the start of study treatment
  • Brain metastases, or spinal cord compression (unless spinal cord compression is asymptomatic, treated and stable and not requiring steroids for at least 4 weeks prior to start of study treatment)
  • Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
  • Any of the following cardiac criteria: i. Mean resting corrected QT interval (QTc) > 470 msec obtained from 3 consecutive ECGs ii. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (eg, complete left bundle branch block, third-degree heart block) iii. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, potential for torsades de pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age, or any concomitant medication known to prolong the QT interval iv. Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or NYHA or Class II to IV heart failure or cardiac ejection fraction measurement of < 50% v. 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 NYHA Grade ≥ 2 vi. Uncontrolled hypotension
  • systolic blood pressure (SBP) <90 mmHg and/or diastolic blood pressure (DBP) <50 mmHg vii. Cardiac ejection fraction outside institutional range of normal or <50% (whichever is higher) as measured by echocardiogram (or multiple-gated acquisition [MUGA] scan if an echocardiogram cannot be performed or is inconclusive) viii. Uncontrolled hypertension (SBP ≥ 160 mmHg or DBP ≥ 95 mmHg).
  • Clinically significant abnormalities of glucose metabolism as defined by any of the following: i. Patients with diabetes mellitus type 1 or diabetes mellitus type 2 requiring insulin treatment ii. HbA1c ≥8.0% (63.9 mmol/mol)
  • Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: i. Absolute neutrophil count < 1.5x 109/L ii. Platelet count < 100x 109/L iii. Haemoglobin < 9 g/dL (< 5.59 mmol/L) iv. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2.5x upper limit of normal (ULN) if no demonstrable liver metastases or > 5x ULN in the presence of liver metastases. Elevated alkaline phosphatase (ALP) is not exclusionary if due to the presence of bone metastases and liver function is otherwise considered adequate in the investigator's judgement v. Total bilirubin > 1.5x ULN (participants with confirmed Gilbert's syndrome may be included in the study with a higher value) vi. Creatinine > 1.5x ULN concurrent with creatinine clearance < 50 mL/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is > 1.5x ULN
  • As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses, or known active infection including hepatitis B, hepatitis C, and HIV
  • unevaluable for both bone and soft tissue progression as defined by meeting both of the following criteria: i. a "superscan" of bone scan, and ii. no soft tissue lesion that can be assessed by RECIST criteria
  • Refractory nausea and vomiting, malabsorption syndrome, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection, or other condition that would preclude adequate absorption of capivasertib
  • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contra-indicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent
  • Evidence of dementia, altered mental status, or any psychiatric condition that would prohibit understanding or rendering of informed consent
  • Previous allogeneic bone marrow transplant or solid organ transplant
  • Known additional malignancy that has had progression or has required active treatment in the last 3 years. Exceptions include basal cell carcinoma of the skin, and squamous cell carcinoma of the skin that has undergone potentially curative therapy
  • Treatment with any of the following: i. Nitrosourea or mitomycin C within 6 weeks of the first dose of study treatment ii. Any investigational agents or study drugs from a previous clinical study within 30 days or 5 half-lives (whichever is longer) of the first dose of study treatment iii. Any other chemotherapy, immunotherapy, immunosuppressant medication (other than corticosteroids) or anticancer agents within 3 weeks of the first dose of study treatment. A longer washout may be required for drugs with a long half-life (eg, biologics) iv. Potent inhibitors or inducers of CYP3A4 within 2 weeks before the start of study treatment (3 weeks for St John's wort), or sensitive substrates of CYP3A4, CYP2C9 and/or CYP2D6 with a narrow therapeutic window within 1 week before the start of study treatment
  • Drugs known to prolong the QT interval within 5 half-lives of the first dose of study treatment
  • History of hypersensitivity to active or inactive excipients of capivasertib, abiraterone, or drugs with a similar chemical structure or class
  • Any restriction or contraindication based on the local prescribing information that would prohibit the use of abiraterone

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A Phase I Trial of Fractionated Docetaxel and Radium 223 in Metastatic Castration-Resistant Prostate Cancer (CRPC)


Condition: Metastatic Castrate Resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03737370

Sponsor: Tufts Medical Center

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  1. Histologically or cytologically confirmed adenocarcinoma of the prostate
  2. Documented metastatic castration resistant disease with PSA progression, radiographic progression, or both, despite medical or surgical castration
  3. Two or more bone metastases detected on skeletal scintigraphy
  4. Eligible for docetaxel chemotherapy
  5. ECOG Performance Status 0-2
  6. Adequate organ function:
  7. Hemoglobin > 10 g/dL
  8. Absolute Neutrophil Count ≥ 1,500 K/mL
  9. Platelet count ≥ 150,000 x 10^9/L
  10. Total bilirubin ≤ 1.5x upper limit of normal range, excluding Gilbert syndrome
  11. Serum AST ≤ 1.5 x upper limit of normal range
  12. Serum ALT ≤ 1.5 x upper limit of normal range
  13. Estimated glomerular filtration rate (GFR) > 30mL/min
  14. Ongoing castration (androgen deprivation therapy or prior orchiectomy)
  15. Male subjects with female sexual partners of childbearing potential must agree to use at least one highly effective methods of birth control.
  16. Ability to understand and willingness to sign an informed consent form prior to initiation of any study procedures.
  17. Age ≥ 18 years

Exclusion Criteria:

  1. Prior radionuclide therapy for CRPC
  2. Prior docetaxel for CRPC. (Permitted if given for castration sensitive disease > 6 months prior).
  3. Antiandrogen therapy within 4 weeks of enrollment. However, patients with primary failure of secondary anti-androgen therapy OR symptomatic progression, objective progression and/or biochemical evidence of rising PSA less than 4 weeks after discontinuation of anti-androgen therapy will not have anti-androgen withdrawal responses and will not be excluded.
  4. Preexisting peripheral neuropathy grade 2 or higher.
  5. Other serious medical condition as judged by the investigator.
  6. Active second malignancy that requires therapy.
  7. Known brain or leptomeningeal metastases
  8. Concurrent enrollment in any other investigational anticancer therapy
  9. Treatment with any myelosuppressive agent within 30 days of enrollment
  10. Presence of bulky visceral metastases, defined as any of the following:
  11. ≥ 4 lung lesions (at least 1cm each in size in the longest diameter) or pulmonary lymphangitic metastasis
  12. Liver metastases with sum of lesion diameters totaling ≥ 5cm
  13. Evidence of neuroendocrine or small cell differentiation on prior biopsy
  14. History of severe hypersensitivity reactions to docetaxel or to drugs formulated with polysorbate 80

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A Phase 3, Randomized, Open-Label, Controlled Study of Cabozantinib (XL184) in Combination With Atezolizumab vs Second Novel Hormonal Therapy (NHT) in Subjects With Metastatic Castration-Resistant Prostate Cancer


Condition: Metastatic Prostate Cancer, Prostate Adenocarcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04446117

Sponsor: Exelixis

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • Men with histologically or cytologically confirmed adenocarcinoma of the prostate
  • Prior treatment with one, and only one, NHT (eg, abiraterone, apalutamide, darolutamide, or enzalutamide) for castration-sensitive locally advanced (T3 or T4) or mCSPC, M0 CRPC, or mCRPC
  • Surgical or medical castration, with serum testosterone ≤ 50 ng/dL (≤ 1.73 nmol/L) at screening
  • Measurable (extrapelvic soft tissue) metastatic disease per Investigator assessment defined by at least one of the following: measurable visceral disease (eg, adrenal, kidney, liver, lung, pancreas, spleen) per RECIST 1.1; OR measurable extrapelvic adenopathy (ie, adenopathy above the aortic bifurcation)
  • Progressive disease at study entry as defined by specific criteria for prostate specific antigen (PSA) progression OR soft tissue disease progression in the opinion of the Investigator (Note: subjects with bone disease progression alone are not eligible)
  • Age ≥ 18 years old or meeting country definition of adult, whichever is older, on the day of consent
  • ECOG performance status of 0 or 1
  • Recovery to baseline or ≤ Grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy in the opinion of the Investigator
  • Adequate organ and marrow function based upon specific laboratory assessments obtained within 21 days prior to randomization
  • Understanding and ability to comply with protocol requirements

Exclusion Criteria:

  • Any prior nonhormonal therapy initiated for the treatment of mCRPC
  • Receipt of abiraterone within 1 week; cyproterone within 10 days; or flutamide, nilutamide, bicalutamide, enzalutamide, or other androgen-receptor inhibitors within 2 weeks before randomization
  • Radiation therapy within 4 weeks (2 weeks for bone metastases) prior to randomization (subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible)
  • Known brain metastases or cranial epidural disease unless adequately treated and clinically stable at least 4 weeks prior to randomization
  • Symptomatic or impending spinal cord compression or cauda equina syndrome
  • Concomitant anticoagulation with oral anticoagulants (some specific exceptions apply)
  • Administration of a live, attenuated vaccine within 30 days prior to randomization
  • Systematic treatment with, or any condition requiring, either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to randomization
  • Uncontrolled, significant intercurrent or recent illness
  • Major surgery within 4 weeks prior to randomization
  • Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per ECG within 21 days before randomization
  • Inability or unwillingness to swallow pills or receive IV administration
  • Previously identified allergy or hypersensitivity to components of the study treatment formulations or history of severe infusion-related reactions to monoclonal antibodies
  • Any other active malignancy at time of randomization or diagnosis of another malignancy within 2 years prior to randomization that requires active treatment (some exceptions apply such as locally curable cancers that have apparently been cured).

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Phase 3, Multicenter, Randomized Study, Evaluating the Efficacy and Tolerability of Focused HIFU Therapy Compared to Active Surveillance in Patients With Significant Low Risk Prostate Cancer


Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03531099

Sponsor: Hospices Civils de Lyon

Phase: Phase 3

Eligibility:

  • Age: minimum 50 Years maximum 80 Years
  • Gender: Male

Inclusion Criteria:

  • Patient having been clearly informed of the study and having accepted, with sufficient reflection time, to participate by signing the informed consent form of the study.
  • Age between 50 and 80 years with a life expectancy of more than 5 years. Patients between the ages of 75 and 80 will need to have G8 score > 14.
  • Initial diagnosis of localized prostate cancer (T1c or T2a) with the following characteristics:
  • Only one Target tumor on MRI on a maximum of 2 contigous sextants. Case allowed:
  • If more than one target tumor on MRI, only one of them must be confirmed by targeted prostate biopsies.
  • If no target tumor on MRI, only 2 contigous sextants must be positive on prostate biopsies
  • A maximum tumor length> 3 mm or at least 3 positive biopsies on all biopsies performed (randomized biopsies and/or MRI/Ultrasound Fusion-Guided Prostate Biopsy).
  • Gleason 6 score (risk group 1 of the D'Amico classification).
  • Tumor positioned so that a safety distance of at least 9 mm from external sphincter can be defined during HIFU-FOCAL treatment in prostate tissue around the target.
  • PSA ≤ 15ng / ml.
  • Patient affiliated with health insurance or beneficiary of an equivalent plan.

Exclusion Criteria:

  • Contraindications to treatment with HIFU-F:
  • Tumor not accessible.
  • Multiple intra prostatic calcifications inducing, on ultrasound, a shadow cone in the prostate preventing the penetration of ultrasound and thus the realization of the treatment.
  • History of pelvic irradiation
  • Presence of an implant (stent, catheter) located less than 1 cm from the treatment area.
  • Fistula of the urinary tract or rectum.
  • Anal or rectal fibrosis, anal or rectal stenosis or other abnormalities making it difficult to insert the Focal One® probe.
  • Anatomical abnormality of the rectum or rectal mucosa.
  • Patient with artificial sphincter, penile prosthesis or intra prostatic implant, eg stent.
  • History of intestinal inflammatory pathology.
  • Uro-genital infection in progress (the infection to be treated before HIFU treatment).
  • Anterior surgery at the level of the anus or rectum making the introduction of the probe impossible.
  • Allergy to latex.
  • Thickness of the rectal wall> 10mm.
  • TURP indication. Bladder neck incision is allowed .
  • Patient with a medical contraindication to Sonovue® injection.
  • Patient with a medical contraindication on MRI.
  • Patient already treated for prostate cancer (hormone therapy, radiotherapy, surgery).
  • History of uncontrolled cancer and / or treated for less than 5 years (with the exception of basal cell skin cancer).
  • History of sclerosis of the bladder neck or urethral stenosis.
  • Patient with a several bleeding risk according to medical advice (patient with oral anticoagulant therapy must receive an alternative therapy if randomized in HIFU-F arm).
  • Patients with unstable neurological pathology.
  • Patient who has been treated for a therapeutic trial within 30 days of enrollment or who wishes to participate in an ongoing study that may interfere with this study.
  • Legal person protected by law.
  • Patient not able to understand the objectives of the study or refusing to comply with postoperative instructions.

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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase IV Study of Apalutamide in Chinese Subjects With Non-Metastatic Castration-Resistant Prostate Cancer (NM-CRPC)


Condition: Prostatic Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04108208

Sponsor: Janssen Research & Development, LLC

Phase: Phase 4

Eligibility:

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

Inclusion Criteria:

  • Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features, with high risk for development of metastases, defined as prostate-specific antigen doubling time (PSADT) less than or equals to (<=) 10 months. PSADT is calculated using at least 3 prostate-specific antigen (PSA) values obtained during continuous androgen deprivation therapy (ADT)
  • Castration-resistant prostate cancer (PC) demonstrated during continuous ADT, defined as 3 PSA rises at least 1 week apart, with the last PSA greater than (>) 2 nanogram per milliliter (ng/mL)
  • Surgically or medically castrated, with testosterone levels of less than (<) 50 nanogram per deciliter (ng/dL). If the participant is medically castrated, continuous dosing with gonadotropin releasing hormone analog (GnRHa) must have been initiated at least 4 weeks prior to randomization and must be continued throughout the study to maintain castrate levels of testosterone
  • Participants who received a first-generation anti-androgen (example: bicalutamide, flutamide, nilutamide) must have at least a 4-week washout prior to randomization and must show continuing disease (PSA) progression (an increase in PSA) after washout
  • At least 4 weeks must have elapsed from major surgery or radiation therapy prior to randomization

Exclusion Criteria:

  • Presence of distant metastases, including central nervous system (CNS) and vertebral or meningeal involvement, or history of distant metastases. Exception: Pelvic lymph nodes <2 centimeter in short axis (N1) located below the iliac bifurcation are allowed
  • Symptomatic loco-regional disease requiring medical intervention, such as moderate or severe urinary obstruction or hydronephrosis, due to primary tumor (example, tumor obstruction of bladder trigone)
  • Prior treatment with cytochrome P450 17 alpha-hydroxylase/17,20-lyase (CYP17) inhibitors (example: abiraterone acetate, orteronel, galerterone, ketoconazole, aminoglutethimide) for PC
  • Prior chemotherapy for PC, except if administered in the adjuvant/neoadjuvant setting
  • History of seizure or condition that may pre-dispose to seizure (example: prior stroke within 1 year prior to randomization, brain arteriovenous malformation, schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy)

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A Phase II Randomized Trial of RAdium-223 and SABR Versus SABR for oligomEtastatic Prostate caNcerS (RAVENS)


Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04037358

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum 100 Years
  • Gender: Male

Inclusion Criteria:

  • Patient must have at least one and up to three asymptomatic metastatic tumor(s) of the bone or soft tissue (with at least one bone metastasis) develop within the past 6-months that are ≤ 5.0 cm or <250 cm3
  • Patient must have had their primary tumor treated with surgery and/or radiation.
  • Histologic confirmation of malignancy (primary or metastatic tumor).
  • PSADT <15 months. PSA doubling time (PSADT) will be calculated using as many PSA values that are available from time of relapse (PSA > 0.2). To calculate PSADT, the Memorial Sloan Kettering Cancer Center Prostate Cancer Prediction Tool will be used. It can be found at the following web site: https://www.mskcc.org/nomograms/prostate/psa-doubling-time.
  • Patient may have had prior systemic therapy and/or ADT associated with treatment of their primary prostate cancer. Patient may have had ADT associated with salvage radiation therapy (to the primary prostate cancer or pelvis is allowed).
  • PSA > 0.5 but <50.
  • Testosterone > 125 ng/dL.
  • Patient must be ≥ 18 years of age.
  • Patient must have a life expectancy ≥ 12 months.
  • Patient must have an ECOG performance status ≤ 2.
  • Patient must have normal organ and marrow function as defined as: Before the first administration of Xofigo, the absolute neutrophil count (ANC) should be ≥ 1.5 x 109/L, the platelet count ≥ 100 x 109/L and hemoglobin ≥ 10 g/dL. * Patient must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • No more than 3 years of ADT is allowed, with the most recent ADT treatment having occurred greater than 6 months prior to enrollment.
  • PSMA-PET/MRI or PSMA-PET/CT scan within the past 6 months with results that demonstrate more disease lesions than baseline CT/Bone Scan
  • Castration-resistant prostate cancer (CRPC).
  • Spinal cord compression or impending spinal cord compression.
  • Suspected pulmonary and/or liver metastases (greater >10 mm in largest axis).
  • Patient receiving any other investigational agents.
  • Patient receiving abiraterone and prednisone.
  • Patient is participating in a concurrent treatment protocol.
  • Serum creatinine > 3 times the upper limit of normal.
  • Total bilirubin > 3 times the upper limit of normal.
  • Liver Transaminases > 5-times the upper limit of normal.
  • Unable to lie flat during or tolerate PET/MRI, PET/CT or SBRT.
  • Prior salvage treatment to the primary prostate cancer or pelvis is allowed.
  • Refusal to sign informed consent.

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A Phase 2 Study of a Checkpoint Inhibitor in Men With Progressive Metastatic Castrate Resistant Prostate Cancer Characterized by a Mismatch Repair Deficiency or Biallelic CDK12 Inactivation


Condition: Metastatic Castration Resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04104893

Sponsor: VA Office of Research and Development

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Subject must be 18 years of age or older at the time the Informed Consent is signed.
  • The subject (or legally acceptable representative if applicable) must provide written informed consent for the trial.
  • Pathologic diagnosis of prostate cancer of adenocarcinoma or small cell histology.
  • Metastatic disease as documented by technetium-99m (99mTc) bone scan or metastatic lesions by computed tomography (CT) or magnetic resonance imaging (MRI) scans (visceral or lymph node disease). CT-portion of FDG-PET/CT or scan may be used for eligibility. NaF PET-CT is an alternative to 99mTc bone scan. If lymph node metastasis is the only evidence of metastatic disease, it must be 1.5 cm in short axis and above the level of the iliac bifurcation. Imaging studies for the purpose of determining eligibility must be completed within 60 days of Day 1.
  • Progressive castration resistant prostate cancer as defined by serum testosterone < 50 ng/mL and one of the following:
  • PSA progression confirmed per Prostate Cancer Clinical Trials Working Group (PCWG3),
  • Radiographic progression of soft tissues according to Response Evaluation Criteria in Solid Tumors, version 1.1 (iRECIST 1.1) modified based on PCWG3, or radiographic progression of bone according to PCWG3.
  • Prior use of a novel AR signaling inhibitor for 4 weeks, including abiraterone acetate plus prednisone/prednisolone, enzalutamide, apalutamide, and/or darolutamide. NOTE: These AR signaling inhibitors may have been used for mCSPC, M0CRPC, and/or mCRPC.
  • Ongoing surgical or medical castration, with testosterone levels of <50 ng/dL. If the subject is being treated with GnRH analogs (subject who has not undergone bilateral orchiectomy), this therapy must have been initiated at least 30 weeks prior to initiation of pembrolizumab and must be continued throughout the study.
  • ECOG PS grade of 0-2.
  • Metastatic lesion that is amenable to biopsy and performed within 180 days of Day 1.
  • dMMR or CDK12-/- as determined by somatic tumor DNA NGS.
  • Either monoallelic or biallelic inactivation of CDK12 on NGS is considered sufficient for eligibility purposes.
  • MMR genes include: MLH1, MSH2, MLH3, PMS1, MSH6, and PMS2.
  • dMMR is established by MSI-H on NGS. However, for "weak" MMR genes, inclusive of PMS2 and MSH6, monoallelic inactivation will be allowed for eligibility purposes if and only if there is at least MSI-low or hypermutation that is concomitantly present.
  • If there is biallelic inactivation of "strong" MMR genes (MLH1 and MSH2), then patients must manifest MSI-H. However, if the tumor DNA utilized for MSI analysis was obtained > 6 months prior to NGS, then the NGS should be repeated to determine if MSI-H has developed. Monoallelic inactivation of "strong" MMR genes will be allowed if MSI-H is present; in this scenario, it is presumed that biallelic inactivation is present but the second inactivating event was not detected due to technical issues such as low sensitivity for copy loss.
  • Adequate organ function:
  • Hemoglobin (hgb) > 9.0 g/dL,
  • Absolute neutrophil count (ANC) > 1500/ uL,
  • Platelets > 100,000/ uL,
  • Total bilirubin 1.5 x ULN OR direct bilirubin ULN for participants with total bilirubin levels >1.5 x ULN
  • ALT and AST 2.5 x ULN ( 5 x ULN for participants with liver metastases) (Child-Pugh class A and B allowed; Child-Pugh class C is excluded).
  • Creatinine < (2.0 mg/dL) during screening evaluation (>2.0 is allowed if EGFR >30 mL/min/1.73 m2).
  • Subject must agree to use contraception during the treatment period plus an additional 120 days after the last dose of study treatment and must refrain from donating sperm during this period.

Exclusion Criteria:

  • Brain metastases.
  • Prior treatment with an anti-PD1, anti-PDL1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
  • Anti-neoplastic therapies for prostate cancer must be completed > 2 weeks prior to Day 1 (initiation of pembrolizumab); chemotherapy must be completed > 4 weeks prior to Day 1.
  • Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks [could consider shorter interval for kinase inhibitors or other short half-life drugs] prior to [randomization /allocation]. 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.
  • Herbal and non-herbal products that may decrease PSA levels other than medical castration and megestrol (up to 40 mg/day is allowed) for hot flashes.
  • 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-CNS disease.
  • 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.
  • If a subject has undergone major surgery, they must have recovered adequately from the toxicities or complications from the intervention within 4 weeks prior to starting therapy.
  • History of non-prostate active malignancy requiring treatment in the 24 months prior to Day 1 except for non-muscle invasive urothelial cancer and non-melanoma skin cancer.
  • Active infection or conditions requiring treatment with antibiotics.
  • Immunosuppressive doses of systemic medications, such as corticosteroids (doses > 10 mg/day prednisone or equivalent), within 2 weeks of Day 1.
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • 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.
  • Active autoimmune disease or a documented history of autoimmune disease that requires immunosuppressive medications within the last two years (e.g., chronic steroids, methotrexate, tacrolimus, etc.).
  • Active or chronic hepatitis B or hepatitis C disease as determined by hepatitis B surface antigen (HBsAg), hepatitis B core antibody, or hepatitis C antibody (anti-HCV) positivity at screening. If positive, further testing of quantitative levels to rule out active infection is required.
  • History of positive test for human immunodeficiency virus (HIV). NOTE: Hepatitis B and C and HIV testing is NOT required during screening.
  • Vaccinated with a live vaccine within 30 days of enrollment.
  • Has severe hypersensitivity ( Grade 3) to pembrolizumab and/or any of its excipients.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Subject is planning 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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Darolutamide Observational Study in Non-metastatic Castration-resistant Prostate Cancer Patients


Condition: Prostate Cancer

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT04122976

Sponsor: Bayer

Phase:

Eligibility:

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

Inclusion Criteria:

  • Men over the age of 18 years
  • Histologically or cytologically confirmed adenocarcinoma CRPC (Castration-Resistant Prostate Cancer) defined by disease progression despite ADT (Androgen-Deprivation Therapy) and may present as a confirmed rise in serum PSA levels (as defined by PCWG3 (Prostate Cancer Working Group 3): Rising PSA values at a minimum of 1-week intervals, and a baseline PSA value ≥ 1.0 ng/mL).
  • No evidence of metastasis based on imaging assessment obtained within 3 months prior to first dose of darolutamide
  • Decision to initiate treatment with darolutamide was made as per investigator's routine treatment practice prior to enrollment in the study
  • Signed informed consent
  • Life expectancy of ≥3 months

Exclusion Criteria:

  • Participation in an investigational program with interventions outside of routine clinical practice
  • Contraindications according to the local marketing authorization
  • Previous treatment with darolutamide (more than 3 days prior to enrollment)

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A Phase 1 Dose Escalation and Expanded Cohort Study of P-PSMA-101 in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC) and Advanced Salivary Gland Cancers (SGC)


Condition: Prostatic Neoplasms, Castration-Resistant, Neoplasms by Histologic Type, Neoplasms, Prostate, Prostate Cancer, Metastatic Castration-resistant Prostate Cancer, Neoplasms, Prostatic Neoplasms, Genital Neoplasms, Male, Urogenital Neoplasms, Neoplasms by Site, Prostatic Disease, Salivary Gland Cancer, Salivary Gland Tumor, Adenoid Cystic Carcinoma, Salivary Duct Carcinoma, Mucoepidermoid Carcinoma, Acinic Cell Tumor

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04249947

Sponsor: Poseida Therapeutics, Inc.

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  • Subjects ≥18 years of age
  • Must have a confirmed diagnosis of mCRPC or SGC
  • Must have measurable disease by RECIST 1.1 or bone only metastases with measurable PSA (≥1 ng/mL) (mCRPC subjects only)
  • Must have progressed by PCWG3 and/or RECIST 1.1 (mCRPC subjects only)
  • Must be willing to practice birth control from screening and for 2 years after the last administration of P-PSMA-101
  • Must have adequate vital organ function within pre-determined parameters
  • Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

Exclusion Criteria:

  • Has inadequate venous access and/or contraindications to leukapheresis
  • Has an active second malignancy in addition to mCRPC or SGC, excluding low-risk neoplasms such as non-metastatic basal cell or squamous cell skin carcinoma
  • Has a history of or active autoimmune disease
  • Has a history of significant central nervous system (CNS) disease, such as stroke or epilepsy
  • Has an active systemic (viral, bacterial or fungal) infection
  • Has received anti-cancer medications (excluding GnRH targeted therapies) within 2 weeks of the time of initiating conditioning chemotherapy
  • Has received immunosuppressive medications (including anti-cancer medications) within 2 weeks of initiating leukapheresis and/or expected to require them while enrolled in the study
  • Has received systemic corticosteroid therapy within 2 weeks of either the required leukapheresis or is expected to require it during the course of the study
  • Has CNS metastases or symptomatic CNS involvement
  • Has a history of significant ocular disease
  • Has a history of significant liver disease or active liver disease
  • Has liver metastases (<5 lesions and maximum diameter
  • Has a history of or known predisposition to HLH or MAS

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CIRCULATING MICRO-RNA (miRNA) AND AR-V7 MUTATIONAL STATUS IN METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (CRPC): PRIMERA+ STUDY (PROSTATE CANCER INNOVATING MARKERS OF EXPECTED RESPONSE TO AGONIST LHRH+ ANDROGEN RECEPTOR INHIBITION


Condition: D011471, D064129, D035683, D009360, D014408

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT04188275

Sponsor: Azienda Ospedaliero-Universitaria Careggi

Phase:

Eligibility:

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

Inclusion Criteria:

  • Castration Resistant Prostate Cancer defined as biochemical or clinical progression under therapy with LHRH agonist and castrate plasma testosterone levels (<20 ng/dl or <1.73 nmol/L)
  • Eligible for medical treatment
  • Age >18 years
  • Informed consentment

Exclusion Criteria:

  • Medical contraindication/refusal to chemotherapy or endocrine therapy
  • Life expectancy inferior to 1 year
  • Previously diagnosed neoplasm

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A Phase Ib/II Study of Copanlisib Combined With Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer


Condition: Metastatic Castration-resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04253262

Sponsor: Brown University

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • 1. Age ≥ 18 years 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 3. Life expectancy of at least 3 months 4. Histologically confirmed prostate cancer. Treatment-emergent small cell/NEPC (neuroendocrine prostate cancer) is allowed, but de novo small cell carcinoma of the prostate is excluded. 5. Progressive metastatic prostate cancer despite castrate levels of testosterone (< 50 ng/dL). 6. Patients may have either non-measurable disease OR measurable disease (by RECIST criteria) 7. Progressive disease during treatment (or within 4 weeks of completion) with abiraterone, enzalutamide, and/or apalutamide based on any one of the following:
  • For patients with measurable disease, progression by the RECIST 1.1 criteria
  • PSA evidence for progressive prostate cancer consists of a PSA level of at least 2 ng/ml which has risen on at least 2 successive occasions, at least one week apart. If the confirmatory PSA value is less than the screening PSA value, then an additional test for rising PSA will be required to document progression for the purposes of eligibility
  • Radionuclide bone scan: At least two new foci consistent with metastatic lesions 8. Testosterone < 50 ng/dL. Patients must continue primary androgen deprivation with an LHRH analogue if they have not undergone bilateral orchiectomy. 9. Prior therapy with taxane in the castrate-sensitive or castration-resistant settings will be allowed. Prior treatment with radium-223 or sipuleucel-T is permitted, but not required. 10. No other systemic therapies for prostate cancer within 21 days prior to cycle 1 day 1 of study therapy or 5 half-lives, whichever is shorter, prior to day 1 of study therapy. 11. Left ventricular ejection fraction (LVEF) ≥ 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) obtained during screening 12. Patients must have adequate organ and bone marrow function within 14 days of inclusion in the study as defined below:
  • Absolute Neutrophil Count ≥ 1,500/mm3
  • Hemoglobin ≥ 9 g/dL
  • Platelets ≥ 100,000 /mm3
  • PT/INR ≤ 1.5 x ULN unless on chronic and stable anticoagulation at time of study entry
  • Bilirubin ≤1.5 x institutional upper limit of normal (ULN) except for unconjugated hyperbilirubinemia or Gilbert's Syndrome, who can have total bilirubin <3.0 mg/dL
  • AST/ALT ≤ 3 x ULN (≤ 5 x ULN if liver metastases present)
  • Lipase ≤ 1.5 x ULN
  • HbA1c < 8.5 %
  • Serum Creatinine ≤ 1.5 X ULN (upper limit of normal) or creatinine clearance ≥ 45 mL/minute (using Cockcroft/Gault formula) 13. Sexually active males must use a condom with spermicide during intercourse while taking the drug and for 6 months after stopping treatment, even if patient is vasectomized to prevent delivery of the drug via seminal fluid. 14. Patients must agree to provide tumor tissue, either fresh or archival specimen of primary tumor and/or metastatic lesion, if available. Availability of tissue will not be required for enrollment. 15. Subjects must have the ability to understand and the willingness to sign a written informed consent prior to registration on study. Subjects should be willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations at the institution. 16. Only during phase 2, patients will be required to have mutations in DNA repair genes based on molecular tests performed on germline DNA, prostate cancer tissue or ctDNA. Qualifying mutations (i.e. deleterious/pathogenic alterations) in at least one of the following genes involved with homologous recombination repair will be required: BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, FANCL, FANCA, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L. Variants of unknown significance in one of the above genes are not eligible.

Exclusion Criteria:

  • 1. History of myelodysplastic syndrome or acute myeloid leukemia. 2. During phase 2, patients must not have received previous treatment with a DNA-damaging cytotoxic chemotherapy (e.g. prior platinum-based chemotherapy and mitoxantrone are not permitted) or PARP inhibitor. Prior treatment with PARP inhibitor is allowed during phase I dose escalation. 3. Untreated leptomeningeal or metastatic CNS disease; patients with treated disease may be eligible if clinically stable for 4 weeks after radiation or surgery including those with history of spinal cord compression that have received definitive treatment. If patients are receiving steroids as adjunct for treatment of leptomeningeal disease or metastatic CNS disease, dose should be stable for 4 weeks prior to day 1 of cycle 1. 4. Clinically significant, uncontrolled heart disease and/or recent events including any of the following:
  • History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) or symptomatic pericarditis within 6 months prior to screening
  • History of documented congestive heart failure (New York Heart Association functional classification III-IV)
  • History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening. Patients with rate-controlled atrial fibrillation or flutter are permitted.
  • QTcF > 470 msec on screening 12-lead ECG
  • Documented cardiomyopathy 5. Clinically significant uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management). For the purpose of this protocol definition of uncontrolled hypertension is based on persistent (≥72 hours) and symptomatic. 6. Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before the start of study medication. However, patients with a venous thrombosis, including a pulmonary embolus, who have been on stable anticoagulation (more than 1 month without bleeding on a stable dose) is permitted. Patients with evidence or history of uncontrolled bleeding diathesis. Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study medication 7. History or concurrent condition of clinically significant interstitial lung disease and/or severely impaired lung function. History of renal failure requiring peritoneal dialysis or hemodialysis. History of cirrhosis Child-Pugh B or C. Intestinal malabsorption. 8. Active, clinically serious infections of CTCAE (v 5.0) Grade ≥ 2 or per investigator discretion. 9. History of uncontrolled human immunodeficiency virus (HIV) infection defined as CD4 < 200 cells/mm3 or detectable viral load is not allowed. 10. Hepatitis B (HBV) or hepatitis C (HCV). All patients must be screened for HBV and HCV up to 28 days prior to study drug start using the routine hepatitis virus laboratorial panel. Patients positive for HBsAg or HBcAb will be eligible if they are negative for HBV-DNA. These patients should receive prophylactic antiviral therapy. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA. 11. Previous or concurrent history of malignancies within 5 years prior to study treatment except for curatively treated cervical carcinoma in situ, non-melanoma skin cancer, superficial bladder cancer (Ta [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria]) or other T1 tumor that has been surgically removed with a low chance of recurrence in the next 3 years. 12. Known hypersensitivity to any of the test drugs, test drug classes, or excipients in the formulation 13. Ongoing substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results. 14. Prior radiation within 7 days of start drug. Prior major surgery, open biopsy or significant trauma within 28 days of start drug. 15. Patients with severe psychiatric illness/social situations that would limit compliance with study requirements in the judgment of study investigator 16. Patient has a history of non-compliance to medical regimen or inability to grant consent 17. Ongoing immunosuppressive therapy. Patients may be receiving up to 10mg/day of prednisone. 18. Radiotherapy or immuno-/chemotherapy less than 2 weeks before start of treatment. A wash-out period of 2 months from radiopharmaceuticals such as radium-223 and 177Lu-PSMA among others will be required. 19. Myeloid growth factors within 14 days prior to treatment. 20. Blood or platelet transfusion less than 7 days before cycle 1 day 1. 21. History of having received an allogeneic bone marrow or organ transplant. 22. Major surgical procedure or significant traumatic injury (as judged by the investigator) within 28 days before start of treatment, or have not recovered from major side effects; open biopsy within 7 days before start of treatment. 23. Anti-arrhythmic therapy for ventricular arrhythmias. Use of amiodarone and propafenone for atrial fibrillation rate control is allowed. 24. Use of CYP3A4 inhibitors and inducers. Copanlisib is primarily metabolized by CYP3A4. Therefore concomitant use of strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, darunavir, indinavir, lopinavir, mifepristone, posaconazole, ombitasvir, idelalisib, cobicistat, atazanavir, ritonavir, indinavir, nelfinavir and saquinavir) and inducers (apalutamide, carbamazepine, enzalutamide, fosphenytoin, phenobarbital, phenytoin, primidone, rifampin) is not allowed. Rucaparib is a moderate inhibitor of CYP1A2 and a weak inhibitor of CYP2C9, CYP2C19 and CYP3A4 and no specific medications is contra-indicated but dose adjustment may be necessary of concurrent medication

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Oligomet-DK. National Danish Protocol. Surgery+ SBRT for M1 Prostate Cancer Patients


Condition: Prostate Cancer Metastatic

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04086290

Sponsor: Peter Busch Østergren

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  1. Age 18 years or older and willing and able to provide informed consent;
  2. Stage cT1 ≤ cT3b, Clinical resectable
  3. Gleason score ≥ 6
  4. M1
  5. ≤ 3 bone metastases localized to the spine, pelvis or humeral/femoral bones as evaluated by 68Ga-PSMA PET/CT and magnetic resonance imaging (MRi)
  6. Absence of PSMA uptake in retroperitoneal lymph nodes, (outside the anatomical region of extended pelvic lymph node dissection as described in the European Association of Urology (EAU) guidelines.
  7. No visceral metastasis
  8. Metastases suitable for stereotactic body radiotherapy
  9. Non symptomatic bone lesions
  10. Eligible for surgery

Exclusion Criteria:

  1. Prior curative intended treatment for prostate cancer
  2. Prior androgen deprivation therapy (ADT)
  3. History of another invasive cancer within 3 years of screening, with the exception of fully treated cancers with a remote probability of recurrence. The medical monitor and investigator must agree that the possibility of recurrence is remote for exceptions.
  4. Eastern Cooperative Oncology Group (ECOG) Performance Status > 1
  5. Evaluated not able to fulfil the study protocol.
  6. Contraindications against MRI

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A Randomized, Parallel Phase II Trial of Hypofractionated Proton Therapy or IMRT for Recurrent, Oligometastatic Prostate Cancer Involving Only Pelvic and/or Para-Aortic Lymph Nodes Following Primary Localized Treatment


Condition: Metastatic Prostate Adenocarcinoma, Oligometastatic Prostate Carcinoma, Prostate Adenocarcinoma, Recurrent Prostate Carcinoma, 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: NCT04190446

Sponsor: Mayo Clinic

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Male; age >= 18 years
  • Histological confirmation of prostate adenocarcinoma
  • Recurrent prostate cancer after prior receipt of primary radiotherapy to the prostate (can also include treatment of splenic vessels [SVs] and lymph nodes [LNs]) or salvage RT to the prostate fossa (can also include prior pelvic RT)
  • Oligometastatic extent of disease
  • Recurrent disease involving lymph nodes as diagnosed with choline positron emission tomography (PET)/computed tomography (CT) or other advanced PET imaging (prostate-specific membrane antigen [PSMA] or flucyclovine)
  • Limited to pelvic and/or retroperitoneal/para-aortic lymph nodes
  • Zubrod performance score (PS) =< 1
  • Signed informed consent

Exclusion Criteria:

  • Bone or visceral metastases present
  • Lymph node metastases beyond the pelvis and/or retroperitoneum
  • Contraindications to RT (e.g., uncontrolled inflammatory bowel disease)
  • Contraindications to androgen suppression
  • Concurrent antineoplastic agents (chemotherapy)
  • Previous or concurrent malignancy other than non-melanoma skin cancer within 5 years of diagnosis of prostate cancer
  • Inability to start the radiation portion of the protocol treatment within 6 months after study enrollment
  • Medical or psychiatric conditions that preclude informed decision-making or compliance with the protocol treatment or follow-up

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DASL-HiCaP: Darolutamide Augments Standard Therapy for Localised Very High-Risk Cancer of the Prostate (ANZUP1801): A Randomised Phase 3 Double-blind, Placebo-controlled Trial of Adding Darolutamide to Androgen Deprivation Therapy and Definitive or Salvage Radiation in Very High Risk, Clinically Localised Prostate Cancer


Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04136353

Sponsor: University of Sydney

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • 1. Men aged 18 years and older, with pathological diagnosis of adenocarcinoma of the prostate 2. EITHER planned for primary RT and judged to be at very high risk for recurrence based on any of the following:
  • Grade Group 5, OR
  • Grade Group 4 AND one or more of the following: clinical T2b-4 OR MRI with seminal vesicle invasion OR extracapsular extension OR PSA* > 20ng/mL, OR
  • Pelvic nodal involvement (involvement of lymph nodes (LNs) at or below the bifurcation of the aorta into the common iliac arteries) defined radiologically as greater than 10mm on short axis using standard CT or MRI, or pathologically confirmed (PSMA PET alone is not considered enough if ≤ 10mm) OR Post-radical prostatectomy ≤ 365 days prior to randomisation and planned for RT with PSA* ≥ 0.1 ng/mL that has risen or remained stable (within ≤ 0.05 ng/mL) since a previous level at least 1 week earlier, judged to be at very high risk for recurrence based on any of the following:
  • Grade Group 5, OR
  • Grade Group 4 AND pT3a or higher, OR
  • Pelvic nodal involvement (involvement of LNs at or below the bifurcation of the aorta into the common iliac arteries) defined radiologically as greater than 10mm on short axis using standard CT or MRI, or pathologically confirmed (PSMA PET alone is not considered enough if ≤ 10mm) * This PSA level must be measured within 60 days prior to randomisation. However, if a participant has already commenced endocrine therapy (ET) for prostate cancer, this PSA level must be measured within 180 days prior to commencing ET. 3. Adequate bone marrow function: Haemoglobin ≥ 100g/L, white cell count (WCC) ≥ 4.0x109/L, absolute neutrophil count (ANC) ≥ 1.5x109/L and platelets > 100 x 109/L 4. Adequate liver function: alanine aminotransferase (ALT) < 2 x upper limit of normal (ULN) and total bilirubin < 1.5 x ULN, (or if total bilirubin is between 1.5
  • 2 x ULN, they must have a normal conjugated bilirubin) 5. Adequate renal function: calculated creatinine clearance > 30 mL/min (Cockroft-Gault) 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0
  • 1 7. Study treatment both planned and able to start within 7 days after randomisation 8. Willing to complete health-related quality of life (HRQL) questionnaires UNLESS is unable to complete because of literacy or limited vision 9. Willing and able to comply with all study requirements, including standard of care treatment such as EBRT, timing and/or nature of required assessments 10. Signed, written informed consent

Exclusion Criteria:

  • 11. Prostate cancer with predominant non-adenocarcinoma features (sarcomatoid or spindle cell or neuroendocrine small cell or squamous cell components or other non-adenocarcinoma) 12. Involvement of LNs by conventional CT imaging superior to the common iliac artery bifurcation, and/or outside the pelvis (distant LNs). LN involvement is defined by histopathological confirmation, or by a short axis measurement > 10mm on standard imaging (CT or MRI, but not PET). 13. Evidence of metastatic disease. Minimum imaging requirements to exclude metastatic disease are diagnostic quality imaging of both the pelvis and the abdomen (CT or MRI), chest (CXR or CT), and a whole body radioisotope bone scan (WBBS).
  • If endocrine therapy (ET) had not started, imaging must be within 60 days prior to randomisation.
  • If ET has been started, imaging must have been performed no more than 60 days prior to starting ET and no more than 30 days after starting ET and prior to randomisation. 14. PSA > 100 ng/mL at any time 15. Any prior use of new generation potent AR inhibition (abiraterone, enzalutamide, apalutamide, darolutamide or similar agents). 16. Prior endocrine therapy for prostate cancer except for the following which are allowed:
  • (i) LHRHA and/or (ii) a first-generation nonsteroidal antiandrogen (NSAA) are allowed if commenced no more than 90 days before randomisation. If an NSAA has been used, it must be stopped before starting study treatment with darolutamide/placebo; and
  • Prior use of 5-alpha reductase inhibitor is allowed and if used it must be stopped before starting study treatment with darolutamide/placebo 17. Bilateral orchidectomy 18. Prior pelvic brachytherapy or other radiotherapy that would result in an overlap of radiotherapy fields that would preclude the required RT 19. History of
  • Loss of consciousness or transient ischemic attack or stroke within 6 months prior to randomisation, or
  • Significant cardiovascular disease within 6 months prior to randomisation: including myocardial infarction, unstable angina, congestive heart failure (NYHA grade II or greater), ongoing arrhythmias of Grade > 2 (CTCAE v5.0), thromboembolic events (e.g. deep vein thrombosis, pulmonary embolism), coronary artery bypass graft. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed. 20. Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of darolutamide, including difficulty swallowing tablets 21. History of another malignancy within 5 years prior to randomisation except for those malignancies treated with curative intent with a predicted risk of relapse of less than 10% including but not limited to non-melanoma carcinoma of the skin; or adequately treated, non-muscle-invasive urothelial carcinoma of the bladder (i.e. Tis, Ta and low grade T1 tumours). All such cases with a history of malignancy within the last 5 years are to be discussed with study team before randomisation. Melanoma in-situ and other adequately treated in-situ neoplasms are not considered malignancies for the purposes of eligibility assessment. 22. Concurrent illness, including severe infection that might jeopardise the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety (HIV infection is not an exclusion criterion if it is controlled with anti-retroviral drugs that are unaffected by concomitant darolutamide) 23. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse 24. Patients who are sexually active with women of child-bearing potential and not willing/able to use medically acceptable and highly effective forms of contraception during study treatment and for at least 4 weeks after completion of study treatment. Contraception must include:
  • Condom use (also required if sexual partner is pregnant), and
  • Additional birth control with low failure rate (less than 1% per year) when used consistently and correctly. E.g. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, true sexual abstinence. True sexual abstinence will only be an acceptable form of contraception when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to study treatment, and withdrawal are not acceptable methods of contraception. 25. Participation in other clinical trials of investigational agents for the treatment of prostate cancer or other diseases 26. Major surgery within 21 days prior to randomisation 27. Patients with history of hypersensitivity to the study treatment

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Identifying the Optimal Biopsy Scheme at MRI Target Biopsy


Condition: Suspicion of Prostate Cancer With a Positive Multiparametric Magnetic Resonance of the Prostate

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04183699

Sponsor: IRCCS San Raffaele

Eligibility:

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

Inclusion Criteria:

  • Male patients, aged between 18 and 80 years old with suspicion of prostate cancer
  • Presence of a positive mpMRI of the prostate (visible lesion PI-RADS ≥ 3)
  • Serum PSA ≤ 20ng/ml
  • Suspected stage ≤ T2 on rectal examination (organ confined prostate)
  • Fit to undergo a prostate biopsy
  • Able to understand and willing to sign a written informed consent document

Exclusion Criteria:

  • Prior positive prostate biopsy
  • Prior treatment of the prostate
  • Prostate volume <30 ml at mpMRI of the prostate
  • More than one lesion at mpMRI of the prostate
  • Contraindication to prostate biopsy

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An Open Label, Randomized, Phase III Study, Evaluating the Efficacy of a Combination of Apalutamide With Radiotherapy and LHRH Agonist in High-risk Postprostatectomy Biochemically Relapsed Prostate Cancer Patients


Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04181203

Sponsor: UNICANCER

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  1. Patients must have signed a written informed consent form prior to any trial specific procedures
  2. Age ≥18 years old and ≤80 years old
  3. Histologically confirmed diagnosis of prostate adenocarcinoma treated primarily with radical prostatectomy
  4. Pathologically proven to be lymph node negative by pelvic lymphadenectomy (N0) or lymph node status pathologically unknown (undissected pelvic lymph nodes [Nx])
  5. Tumor stage pT2, pT3 or pT4* (*only in case of bladder neck involvement)
  6. Patients should have no clinical and radiological signs (18FCH-PET CT-scan or 68Ga-PSMA-PET CT-scan) of metastatic disease. Patients with a local relapse detected on PET CT-scan can be randomized
  7. Eastern Cooperative Oncology Group (ECOG) performance status ≤1
  8. PSA ≤0.5 ng/mL after radical prostatectomy (dosage performed within 3 months after surgery)
  9. PSA ≥0.2 ng/mL and ≤2 ng/mL at the time of randomization with an elevation of PSA over three consecutive assays
  10. At least 3 months between radical prostatectomy and inclusion
  11. High-risk features as defined by at least one of these characteristics: PSA at relapse >0.5 ng/mL or Gleason score >7 or tumor stage pT3b or resection margins R0 or PSA doubling time ≤6 months
  12. Adequate renal function: serum creatinine <1.5 x upper limit of normal (ULN) or a calculated corrected creatinine clearance ≥60 mL/min according to the Cockcroft-Gault formula, creatinemia <2 ULN
  13. Adequate hepatic function: total bilirubin ≤1.5 x ULN (unless documented Gilbert's syndrome), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN
  14. Patients with QTc prolongation <500 ms, inclusion should considered after close benefit/risk assessment and cardiologist advice
  15. Patients with female partners of reproductive potential should agree to use effective contraceptive method during treatment period and for 3 months after the last dose of apalutamide or for 6 months after the last fraction of radiotherapy
  16. Patients must be willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
  17. Patients must be affiliated to the Social Security System

Exclusion Criteria:

  1. Histologically proven lymph nodes involvement at initial lymphadenectomy: pN1, pN2, pN3
  2. Previous treatment with hormone therapy for prostate cancer
  3. Histology other than adenocarcinoma
  4. Surgical or chemical castration
  5. Other malignancy except adequately treated basal cell carcinoma of the skin or other malignancy from which the patient has been cured for at least 5 years
  6. Previous pelvic radiotherapy
  7. History of Inflammatory bowel disease or any malabsorption syndrome or conditions that would interfere with enteral absorption
  8. Uncontrolled hypertension (defined as systolic blood pressure (BP) ≥140 mmHg or diastolic BP ≥90 mmHg). Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
  9. Clinically significant history of liver disease consistent with Child-Pugh class B or C
  10. History of seizure or condition that may pre-dispose to seizure (including, but not limited to prior stroke, transient ischemic attack or loss of consciousness ≤1 year prior to randomization; brain arteriovenous malformation or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)
  11. Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry
  12. Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g pulmonary embolism, cerebrovascular accident including transient ischemic attacks) or clinically significant ventricular arrhythmias within 6 months prior to randomization
  13. 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 >500 ms at baseline
  14. Medications known to prolong QTc
  15. Known hypersensitivity to apalutamide or to any of its components
  16. Galactosemia, Glucose-galactose malabsorption or lactase deficiency
  17. Inability or willingness to swallow oral medication
  18. Individual deprived of liberty or placed under the authority of a tutor
  19. Patients already included in another therapeutic trial with an experimental drug or having been given an experimental drug within the 30 days before inclusion

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A Phase II Study of the Addition of Opaganib to Androgen Antagonists in Patients With Prostate Cancer Progression on Enzalutamide or Abiraterone


Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04207255

Sponsor: Medical University of South Carolina

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • 1. Patient must have mCRPC. Each patient must have:
  • Tissue diagnosis documented by pathology report, or clinic note attesting to same.
  • Radiographically-demonstrated metastases
  • Patients must have adenocarcinoma, or ductal carcinoma, or combinations of these two entities 2. Voluntary, signed and dated, institutional review board (IRB)-approved informed consent form in accordance with regulatory and institutional guidelines. 3. Documented progression during treatment with enzalutamide or abiraterone, as determined by the enrolling investigator. 4. Testosterone level documented to be less than 50ng/ 5. 18 years of age or older. 6. ECOG performance status of 0-2. 7. Acceptable liver function:
  • Bilirubin ≤ 1.5 times upper limit of normal (CTCAE Grade 1 baseline)
  • AST (SGOT) & ALT (SGPT) ≤ 3 x ULN (CTCAE Grade 1 baseline)
  • Subjects with Gilbert's syndrome may be included if the total bilirubin is <3x ULN and the direct bilirubin is within normal limits 8. Acceptable kidney function indicated by serum creatinine ≤ 1.5 X ULN (CTCAE Grade 1 baseline) 9. Acceptable hematologic status:
  • Absolute neutrophil count ≥ 1000 cells/mm3,
  • Platelet count ≥ 75,000 (plt/mm3) (CTCAE Grade 1 baseline)
  • Hemoglobin ≥ 9.0 g/dL. 10. Fasting blood glucose of <165mg/dL 11. Urinalysis: no clinically significant abnormalities 12. International normalized ratio (INR) ≤1.7 13. Well-controlled blood pressure as determined by the treating investigator 14. Patients requiring narcotic analgesics must be on stable doses for at least 2 weeks prior to study entry.

Exclusion Criteria:

  1. New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG.
  2. Underlying psychiatric disorder requiring hospitalization within the last two years.
  3. Clinically significant neurological disorder (Parkinson's disease, dementia, multiple sclerosis), as determined by the enrolling investigator.
  4. Active, uncontrolled bacterial, viral or fungal infection, requiring systemic therapy.
  5. Treatment with radiation therapy, surgery, or investigational therapy within 28 days prior to registration.
  6. Unwillingness or inability to comply with procedures required in this protocol.
  7. Serious nonmalignant disease that could compromise protocol objectives in the opinion of the Investigator.
  8. Patients who are receiving coumadin, apixaban, argatroban or rivaroxaban. Patients who are receiving other drugs that are sensitive substrates of CYP450 1A2, 3A4, 2C9, 2C19 or 2D6, or strong inhibitors or inducers of all major CYP450 isozymes that cannot be stopped at least 7 days or 5 half-lives (whichever is longer) before starting treatment with opaganib may be treated on this study with careful monitoring for toxic effects or loss of efficacy of the relevant drug. A list of commonly used drugs that are sensitive substrates of CYP450 1A2, 3A4, 2C9, 2C19 or 2D6, or strong inhibitors or inducers of all major CYP450 isozymes with the half-life of each drug identified, is included as an Appendix C.
  9. Patients who are currently participating in any other clinical trial of an investigational product.
  10. Other primary malignancy requiring systemic treatment within past 5 years except carcinoma in situ of the cervix or urinary bladder or non-melanoma skin cancer.
  11. Any other mental incapacitation or psychiatric illness that would preclude study participation, as determined by the enrolling investigator.
  12. Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study.

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Postoperative Hypofractionated Radiation Therapy and Hormonal Therapy in Patients With Prostate Cancer: A Phase II Trial


Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04249154

Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Histologically proven high risk (any of the following risk factors: surgical positive margins; extra-capsular extension; seminal vesicle involvement, Gleason score >7) adenocarcinoma of the prostate after a radical prostatectomy as primary treatment (adjuvant group), with pathologically negative lymph nodes dissection or clinically negative lymph nodes by imaging [pelvic and abdominal computed tomography (CT) scan, or magnetic resonance imaging (MRI)]. Lymphadenectomy is not mandatory. Any type of prostatectomy will be permitted. For this group of patients, the PSA level at time of entry must be below 0.4 ng/ml
  • Histologically proven adenocarcinoma after a radical prostatectomy with pathologically negative lymph nodes (lymphadenectomy is not mandatory) or clinically negative lymph nodes by imaging (pelvic and abdominal CT scan, or MRI or) and evidence of biochemical failure (defined as two consecutives rises of the PSA, at any PSA level). PSA upper limit post-prostatectomy must be below 2.0 ng/ml (salvage group). Any type of prostatectomy will be permitted
  • Negative bone metastases proven by bone scan. The use of proton emission tomography (PET) fluoride is allowed
  • History and physical examination (including digital rectal exam) within 90 days prior of registration
  • Adequate marrow reserve defined as: Hemoglobin ≥ 10 g/dl (patients may be transfused in order to achieve this level); Platelets ≥ 100 000 cells/mm3 and a white blood cell count of ≥ 4000 cells/ml3
  • AST or ALT <2 x the upper limit of normal
  • PSA and testosterone levels within one month of registration Age ≥ 18
  • Zubrod Performance Status 0-1
  • Patients must sign a study-specific consent form

Exclusion Criteria:

  • Previous exposure to androgen deprivation
  • Chemotherapy before or after prostatectomy
  • Prior pelvic radiotherapy
  • Previous malignancies (except non-melanomatous skin cancer) unless disease-free >5 years
  • Severe, active medical condition that makes the use of any of the therapies of the study not recommended

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Developing and Testing an Interactive Decision Aid for Newly Diagnosed Prostate Cancer Patients


Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04260737

Sponsor: Reykjavik University

Eligibility:

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

Inclusion Criteria:

  • Newly diagnosed with localized prostate cancer.

Exclusion Criteria:

  • Reads and understands Icelandic
  • Can give informed consent

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Prostatic Artery Embolization (PAE) in Patients With Advanced Prostate Cancer: A Pilot Study.


Condition: Prostate Cancer, Bladder Outlet Obstruction

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03457805

Sponsor: Dominik Abt

Eligibility:

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

Inclusion Criteria:

  • Advanced PCA (i.e., locally advanced, metastatic, combination of both. This includes T3-4, any T in case of N1 and any T in case of M1a/b/c)
  • PAE is indicated for the treatment of Lower urinary tract symptoms like bladder outlet obstruction or recurrent prostatic bleeding.
  • IPSS at baseline ≥ 8
  • Witten informed consent

Exclusion Criteria:

  • Curative treatment of PCA intended
  • Contraindications for MRI
  • Renal impairment (GFR < 30ml/min)
  • Allergy to i.v. contrast medium
  • Vascular conditions that seem to make successful PAE impossible (e.g. severe atherosclerosis, severe tortuosity in the aortic bifurcation or internal iliac vessels)
  • Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant.
  • Drug-treatments for advanced prostate cancer (e.g., hormonal therapy or chemotherapy) established within 30 days prior to PAE.

View trial on ClinicalTrials.gov


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