Prostate Cancer

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Advanced ChemoHormonal Therapy for Treatment Naïve Metastatic Prostate Cancer: Apalutamide and Abiraterone Acetate With Prednisone and Androgen Deprivation Therapy After Treatment With Docetaxel and Androgen Deprivation Therapy


Condition: Castration-Sensitive Prostate Carcinoma, Metastatic 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: NCT04267887

Sponsor: OHSU Knight Cancer Institute

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed prostate cancer OR a strong suspicion of prostate cancer as evidenced by metastatic disease in a pattern consistent with prostate cancer (such as blastic lesions on a nuclear medicine bone scan or lymphadenopathy on the computed tomography [CT] scan) AND a PSA > 50 ng/mL
  • High risk disease (defined as meeting 2 of the 3: (1) visceral metastatic disease, (2) 3 or more bone lesions, (3) Gleason 8-10) at the time diagnosed metastatic
  • If a patient has received androgen deprivation therapy (ADT) for neoadjuvant or adjuvant therapy at least 24 months MUST have elapsed since its use to day 1 of restarting ADT for metastatic castration sensitive disease
  • ADT sensitive disease- no evidence of rising PSA or new metastatic deposits since starting ADT
  • Have completed up to 6 cycles of docetaxel since developing metastatic castration sensitive disease with no more than 12 weeks elapsed since day 21 of the final cycle
  • All races and ethnic groups will be included
  • Life expectancy of greater than 18 months
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Hemoglobin > 9.0 g/dL, independent of transfusion and/or growth factors
  • Leukocytes > 3,000/uL
  • Absolute neutrophil count > 1,500/uL
  • Platelets >= 100,000 x 10^9/uL, independent of transfusion and/or growth factors
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (Note: In subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 x ULN, subject may be eligible)
  • Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) < 2.5 x institutional upper limit of normal
  • Albumin > 3 g/dL
  • Estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m^2; per Modification of Diet in Renal Disease (MDRD) calculation or institutional standard
  • Potassium >= 3.5 mmol/L
  • Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to day 1 of study
  • Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug
  • Ability to understand, and the willingness to sign, a written informed consent document, as well as comply with study requirements

Exclusion Criteria:

  • Subjects who are unwilling to stop taking saw palmetto, PC-SPECs or other herbal agents known to affect the PSA
  • Patients may not have received any other investigational agents within 30 days prior to day 1 of study
  • Prior exposure to apalutamide, enzalutamide, abiraterone acetate, darolutamide, or any other second-generation antiandrogen therapy
  • Note: prior exposure to bicalutamide, flutamide, nilutamide, or any other first-generation androgen receptor antagonist is permitted. No washout is required. Subjects may be on one of these at the time of consent, but it must be stopped prior to day 1 of study treatment. These drugs are frequently used in the newly diagnosed metastatic setting to blunt the effect of the testosterone spike
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to apalutamide or other agents used in the study
  • Subject has another active malignancy other than non-melanomatous skin cancer (unless it is metastatic) or superficial bladder cancer
  • Either of the following:
  • Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system [CNS] or meningeal disease which may require treatment with surgery or radiation therapy)
  • Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure or left ventricular ejection fraction < 50%, 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 day 1 of study
  • Current evidence of any of the following:
  • Uncontrolled hypertension
  • Gastrointestinal disorder affecting absorption
  • Active infection (e.g. human immunodeficiency virus [HIV] or viral hepatitis)
  • Any chronic medical condition requiring a higher dose of corticosteroid than a total of 10 mg prednisone/prednisolone daily
  • Any condition that in the opinion of the investigator, would preclude participation in this study.
  • Avoid concomitant strong CYP3A4 inducers during abiraterone acetate treatment. If a strong CYP3A4 inducer must be co-administered, increase the abiraterone acetate dosing frequency to twice a day only during the co-administration period (e.g., from 1,000 mg once daily to 1,000 mg twice a day).
  • Avoid co-administration of abiraterone acetate with CYP2D6 substrates that have a narrow therapeutic index. If an alternative treatment cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate
  • Baseline moderate and severe hepatic impairment (Child Pugh Class B & C)
  • Inability to stop a prohibited medication:
  • Atypical antipsychotics (e.g. clozapine, olanzapine, risperidone, ziprasidone)
  • Bupropion
  • Lithium
  • Meperidine and pethidine
  • Phenothiazine antipsychotics (e.g. chlorpromazine, mesoridazine, thioridazine)
  • Tricyclic antidepressants (e.g. amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine
  • Tramadol

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Prostate-cancer Treatment Using Stereotactic Radiotherapy for Oligometastases Ablation in Hormone-sensitive Patients - a GETUG-AFU Phase III Randomized Controlled Trial


Condition: Oligometastatic Hormone Sensitive Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04115007

Sponsor: UNICANCER

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • 1. Histologically proven adenocarcinoma of the prostate (any T stage, Gleason score or prostate-specific antigen (PSA) level); 2. Defined as M1 based on the presence of at least one bone or lung metastasis; 3. Diagnostic workup including functional imaging (F or C-Choline-PET/CT or Prostate Specific Membrane Antigen (PSMA) PET/CT or whole body MRI)
  • done prior to the start of hormonal therapy; 4. With up to 5 asymptomatic or paucisymptomatic metastatic sites including at least one bone or pulmonary lesion +/- nodal mestastases. Are counted as a "separate" metastatic site :
  • each bone lesion, whatever the location (including pelvic localization), except if two lesions show hyperfixation in the same bone and are located < 1cm from each other they can be counted as one lesion
  • each node or nodal area located outside the true pelvis with a small diameter of 1cm or greater or with univoqual abnormal function imaging (PET Scan hyperfixation or hypersignal in whole body MRI); if multiple nodes are in close vicinity (<1cm distance between them and <4cm in total distance including the nodes, amenable to one SBRT treatment) they can be counted as one lesion
  • and patients with lung metastasis can be included 5. Patients with a previous prostatectomy or radiotherapy to the prostate and/or pelvic lymph nodes are eligible provided they have no active disease within the irradiated areas, based on functional imaging findings; 6. Age ≥18 years; 7. Eastern Cooperative Oncology Group (ECOG) ≤2; 8. Suitable for long term anti androgen therapy; 9. Patient not suitable for docetaxel or abiraterone can be included; 10. Patient that have started long term hormonal therapy are eligible if hormonal therapy has been initiated less than 2 months before randomization; 11. Patients must agree to use adequate contraception methods for the duration of study treatment and for 6 months after completing treatment; 12. Patient must have received the information sheet and signed the consent form; 13. Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures; 14. Patient must be affiliated to the social security system. NON-INCLUSION CRITERIA: 1. Patient with more than 5 metastatic sites; 2. Patient with metastatic sites other than bone, lymph nodes or lung; 3. Metastases not amenable to radiotherapy treatment with high/curative doses by multidisciplinary meeting [i.e. SBRT as per protocol or curative doses using moderate hypofractionation (55-60Gy/20) or conventional fractionation (≥74 Gy)] (e.g. gross epidural involvement, involvement of three contiguous vertebral bodies, major soft tissue involvement, and previous radiation treatment); 4. Metastases requiring immediate treatment due to significant pain (use of opioid medication), or at risk of fracture or neurological deficit; 5. Prior radiotherapy or focal ablative treatment (cryotherapy, radiofrequency ablation,…) to metastatic lesions; 6. Castrate testosterone level <50 ng/dL or ≤0.50 ng/mL or 1.73 nmol/L prior use of ADT; 7. Prior invasive (except non-melanoma skin cancer) malignancy unless disease-free for ≥5 years; 8. Contra-indication to MRI (needed for spinal SBRT); 9. Persons deprived of their liberty or under protective custody or guardianship; 10. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons; 11. Participation in another therapeutic trial within 30 days prior to randomization.

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A Randomized, Controlled, Multicenter, Open-label Study to Investigate the Efficacy and Safety of Adding Apalutamide to Radiotherapy and LHRH Agonist in High-Risk Patients With PSMA-PET-Positive Hormone-Sensitive Prostate Cancer, With an Observational Follow-up of PSMA-PET-Negative Patients


Condition: Prostatic Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04557059

Sponsor: Janssen Pharmaceutica N.V., Belgium

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the prostate
  • Previously treated with radical prostatectomy with or without lymph node dissection and any post-operative prostate-specific antigen (PSA) measurement of less than (<) 0.1 nanogram/milliliter (ng/mL) between Week 6 and Week 20
  • Be able to swallow whole the study drug tablets or follow the instructions for admixing with apple sauce
  • Prostate specific membrane antigen-positron emission tomography (PSMA-PET) must be performed at screening: Patients who are PSMA-PET-positive for at least one loco-regional (pelvic) lesion with or without distant (extra-pelvic) lesions at screening, as determined by Blinded Independent Central Review (BICR), will be eligible to be randomized to either arm of the Interventional Cohort.The investigators will be blinded to the location of the PSMA-PET lesions after randomization and patients who are PSMA-PET-negative for any prostate cancer lesions (that is no loco-regional lesion and no distant lesion) at screening, as determined by BICR, will be eligible for inclusion in the Observational Cohort
  • Biochemically recurrent prostate cancer after RP with a high risk of developing metastasis defined as pathological Gleason score greater than or equal to (>=) 8 evaluated from prostate tissue specimen at radical prostatectomy, OR PSADT less than or equal to (<=) 12 months at the time of screening
  • No evidence of prostate cancer metastases on screening CT/MRI of the chest/abdomen/pelvis, Technetium 99m [99mTc] whole-body bone scan. Participants with a single bone lesion on 99mTc whole-body bone scan should have confirmatory imaging by CT or MRI; if the confirmatory scan confirms the bone lesion, the patient should be excluded from the study. Conventional images (99mTc-bone scan and CT/MRI) from the screening will be sent to BICR for confirmation of non-metastatic prostate cancer before randomization
  • Eastern Cooperative Oncology Group Performance Status Grade 0 or 1

Exclusion Criteria:

  • History of pelvic radiation for malignancy
  • Previous treatment with androgen deprivation therapy (ADT) for prostate cancer
  • Previously treated for biochemical recurrence (BCR) prostate cancer (previous surgical treatment of one or more loco-regional lesions is allowed)
  • Prior treatment with a CYP17 inhibitor (example, oral ketoconazole, orteronel, abiraterone acetate, galeterone) or any androgen receptor (AR) antagonist including bicalutamide, flutamide, nilutamide, apalutamide, enzalutamide or darolutamide and any other medications that may lower androgen levels (estrogens, progestins, aminoglutethimide, etc.), including bilateral orchiectomy
  • Known or suspected contraindications or hypersensitivity to apalutamide, Luteinizing Hormone-Releasing Hormone (LHRH) agonist or any of the components of the formulations
  • Prior chemotherapy for prostate cancer
  • Any evidence of prostate cancer metastasis on computed tomography/magnetic resonance imaging (CT/MRI) of the chest/abdomen/pelvis or 99mTc whole-body bone scan, at any time prior to screening

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Phase 4 Study of Exploring Circulating Tumor DNA (ctDNA) of Metastatic Castration-sensitive Prostate Cancer (mCSPC) Patients Receiving Apalutamide in Japan


Condition: Metastatic Castration-sensitive Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04601441

Sponsor: Kindai University

Phase: Phase 4

Eligibility:

  • Age: minimum 20 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  • Men aged ≥20 years.
  • Participant has documented diagnosis of metastatic PC with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology.
  • Participant has metastatic PC that is castration naïve or castration sensitive and is permitted to receive less than 6-months ADT or CAB before registration and less than 36-months neoadjuvant or adjuvant hormonal therapy.
  • If a participant is treated with ADT or CAB, he has maintained a response to hormonal therapy of stable disease or better, by investigator assessment of imaging and PSA.
  • Participant is willing to receive apalutamide for mCSPC in the participating site of this study.
  • Participant is of Japanese nationality.
  • Participant must sign an ICF indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.

Exclusion Criteria:

  • Participant does not agree to assess ctDNA including 73 PC driver genes, SNPs, and HLA typing.
  • Participant has received any prior therapy of abiraterone, docetaxel, enzalutamide, apalutamide or darolutamide.
  • Participant has known allergies, hypersensitivity, or intolerance to apalutamide or its excipients (refer to the package insert).
  • Participant has contraindications to the use of ADT based on routine treatment.
  • Participant has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the evaluation of active double cancer, etc.

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TALAPRO-3: A PHASE 3, RANDOMIZED, DOUBLE-BLIND, STUDY OF TALAZOPARIB WITH ENZALUTAMIDE VERSUS PLACEBO WITH ENZALUTAMIDE IN MEN WITH DDR GENE MUTATED METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER


Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04821622

Sponsor: Pfizer

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • 1. Male participants at least 18 years of age at screening (20 years for Japan, 19 years for Republic of Korea). 2. Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, small cell or signet cell features. If the participant does not have a prior histological diagnosis, a baseline de novo biopsy must be used to confirm the diagnosis and may also be used to support biomarker analysis. 3. Confirmation of DDR gene mutation status by prospective or historical analysis (with sponsor pre-approval) of blood (liquid biopsy) and/or de novo or archival tumor tissue using FoundationOne Liquid CDx or FoundationOne CDx. 4. Willing to provide tumor tissue when available (de novo or archived) for retrospective molecular profiling analysis, if not already provided as part of inclusion criterion 3. 5. Unless prohibited by local regulations or ethics committee decision, consent to a saliva sample collection for retrospective sequencing of the same DDR genes tested on tumor tissue and blood (liquid biopsy), or a subset thereof, and to serve as a germline control in identifying tumor mutations. 6. Ongoing ADT with a GnRH agonist or antagonist for participants who have not undergone bilateral orchiectomy must be initiated before randomization and must continue throughout the study. 7. Metastatic prostate cancer documented by positive bone scan (for bone disease) or metastatic lesions on CT or MRI scan (for soft tissue). Participants whose disease spread is limited to regional pelvic lymph nodes are not eligible. Note: a finding of superscan at baseline is exclusionary. 8. Prior treatment of mCSPC with docetaxel is not permitted. 9. Treatment with estrogens, cyproterone acetate, or first-generation anti-androgens is allowed until randomization. 10. Other prior therapy allowed for mCSPC; ≤3 months of ADT (chemical or surgical) with or without approved NHT in mCSPC (ie, abiraterone + prednisone, apalutamide, or enzalutamide), if required prior to randomization, with no radiographic evidence of disease progression or rising PSA levels prior to Day 1. 11. Participant may have received palliative radiation or surgery for symptomatic control secondary to prostate cancer, which should have been completed at least 2 weeks prior to randomization. NOTE: Radical prostatectomy or definitive radiotherapy to the primary tumor for metastatic castration-sensitive prostate cancer with curative intent is not permitted. 12. ECOG performance status 0 or 1. 13. Adequate organ function within 28 days before the first study treatment on Day 1, defined by the following:
  • ANC ≥1500/µL, platelets ≥100,000/µL, or hemoglobin ≥9 g/dL (may not have received growth factors or blood transfusions within 14 days before obtaining the hematology laboratory tests at screening).
  • Total serum bilirubin <1.5 × ULN (<3 × ULN for participants with documented Gilbert syndrome or for whom indirect bilirubin concentrations suggest an extrahepatic source of elevation).
  • AST or ALT <2.5 × ULN (<5 × ULN if liver function abnormalities are due to hepatic metastasis).
  • Albumin >2.8 g/dL.
  • eGFR ≥30 mL/min/1.73 m2 by the MDRD equation. 14. Sexually active participants that in the opinion of the investigator are capable of ejaculating, must agree to use a condom when having sex with a partner (female or male) from the time of the first dose of study treatment through 4 months after last dose of study treatment (or, if talazoparib/placebo has been stopped more than a month earlier than enzalutamide, through 3 months after last dose of enzalutamide). Must also agree for female partner of childbearing potential to use an additional highly effective form of contraception from the time of the first dose of study treatment through 4 months after last dose of study treatment (or, if talazoparib / placebo has been stopped more than a month earlier than enzalutamide, through 3 months after last dose of enzalutamide) when having sex. 15. Must agree not to donate sperm from the first dose of study treatment to 4 months after the last dose of study treatment (or, if talazoparib/placebo has been stopped more than a month earlier than enzalutamide, through 3 months after last dose of enzalutamide). 16. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures, including being able to manage electronic diaries. The PRO assessments are not required to be completed if a patient does not understand the language(s) available for a specific questionnaire and/or cannot complete the specific questionnaire independently. 17. Capable of giving signed informed consent. 18. For France only: Participants affiliated with the social security system or beneficiaries of an equivalent system.

Exclusion Criteria:

  • 1. Other acute or chronic medical (concurrent disease, infection, including chronic stable HIV, HBV, or HCV infection, or co-morbidity) or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that interferes with a participant's ability to participate in the study, may increase the risk of associated with study participation or study treatment administration, or may interfere with the interpretation of study results, and, in the investigator's judgment, make the participant inappropriate for entry into the study. HIV/HBV/HCV testing is not required unless mandated by local health authority. 2. History of seizure or any condition (as assessed by investigator) that may predispose to seizure (eg, prior cortical stroke, significant brain trauma), including any history of loss of consciousness or transient ischemic attack within 12 months of randomization. 3. Major surgery (as defined by the investigator) within 4 weeks before randomization. 4. Known or suspected brain metastasis or active leptomeningeal disease. 5. Symptomatic or impending spinal cord compression or cauda equina syndrome. 6. Any history of MDS, AML, or prior malignancy except for the following:
  • Carcinoma in situ or non-melanoma skin cancer.
  • A cancer diagnosed and treated ≥3 years before randomization with no subsequent evidence of recurrence.
  • American Joint Committee on Cancer Stage 0 or Stage 1 cancer <3 years before randomization that has a remote probability of recurrence in the opinion of the investigator and the sponsor. 7. In the opinion of the investigator, any clinically significant gastrointestinal disorder affecting absorption. 8. Clinically significant cardiovascular disease, including any of the following:
  • Myocardial infarction or symptomatic cardiac ischemia within 6 months before randomization.
  • Congestive heart failure New York Heart Association class III or IV.
  • History of clinically significant ventricular arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsade de pointes) within 1 year before screening.
  • History of Mobitz II second degree or third-degree heart block unless a permanent pacemaker is in place.
  • 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 electrocardiogram.
  • Uncontrolled hypertension as indicated by systolic blood pressure >170 mm Hg or diastolic blood pressure >105 mm Hg at screening. However, participants can be rescreened after adequate control of blood pressure is achieved. 9. Active COVID-19 infection detected by viral test or based on clinical diagnosis (as assessed by investigator). Asymptomatic participants with no active COVID-19 infection detected but positive antibody tests, indicating past infection are allowed. 10. Prior ADT in the adjuvant/neoadjuvant setting, where the completion of ADT was less than 12 months prior to randomization and the total duration of ADT exceeded 36 months. 11. Participant received treatment with systemic glucocorticoids greater than the equivalent of 10 mg per day of prednisone within 4 weeks prior to randomization, intended for the treatment of prostate cancer. 12. Any previous treatment with DNA-damaging cytotoxic chemotherapy (ie, platinum based therapy) within 5 years prior to randomization, except for indications other than prostate cancer. 13. Prior treatment with a PARPi, or known or possible hypersensitivity to enzalutamide, any of enzalutamide capsule excipients or to any talazoparib/placebo capsule excipients. 14. Prior treatment in any setting with NHT, except as described in Inclusion Criterion #10. 15. Current use of potent P-gp inhibitors within 7 days prior to randomization. 16. Treatment with any investigational study intervention within 4 weeks before randomization. Exception: COVID-19 vaccines authorized under an emergency use authorization (or equivalent) can be administered without a washout period. 17. Baseline 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, QTcF interval >470 msec, complete LBBB, signs of an acute or indeterminate age myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, second or third degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If the baseline uncorrected QT interval is >470 msec, this interval should be rate-corrected using the Fridericia method and the resulting QTcF should be used for decision making and reporting. If QTc exceeds 470 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTc or QRS values should be used to determine the participant's eligibility. Computer-interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding participants. 18. Investigator site staff or Sponsor employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members. 19. For France only: Persons deprived of their liberty by a judicial or administrative decision, persons undergoing psychiatric care, as well as adults subject to a legal protection measure (guardianship, curatorship, and safeguard of justice) covered by Articles 1121-6 to 1121-8 of the Public Health Code.

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A Phase 3, Open-Label, Randomized Study Evaluating Metastatic Castrate Resistant Prostate Cancer Treatment Using PSMA [Lu-177]-PNT2002 Therapy After Second-line Hormonal Treatment (SPLASH)


Condition: Metastatic Castration-Resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04647526

Sponsor: POINT Biopharma

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  1. Male aged 18 years or older.
  2. Histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate.
  3. Ineligible or averse to chemotherapeutic treatment options.
  4. Patients must have progressive mCRPC at the time of consent based on at least 1 of the following criteria:
  5. Serum/plasma PSA progression defined as increase in PSA greater than 25% and >2 ng/mL above nadir, confirmed by progression at 2 time points at least 3 weeks apart.
  6. Soft-tissue progression defined as an increase ≥20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or a new lesion.
  7. Progression of bone disease defined as the appearance of two or more new lesions by bone scan.
  8. Progression on previous treatment with one ARAT (abiraterone or enzalutamide or darolutamide or apalutamide) in either the CSPC or CRPC setting.
  9. PSMA-PET scan (i.e., 68Ga-PSMA-11 or 18F-DCFPyL) positive as determined by the sponsor's central reader.
  10. Castrate circulating testosterone levels (<1.7 nmol/L or <50 ng/dL).
  11. Adequate organ function, independent of transfusion: a. Bone marrow reserve: i. White blood cell (WBC) count ≥2.5 × 10^9/L OR absolute neutrophil count (ANC) ≥1.5 × 10^9/L. ii. Platelets ≥100 × 10^9/L. iii. Hemoglobin ≥8 mmol/L. b. Liver function: i. Total bilirubin ≤1.5 × institutional upper limit of normal (ULN). For patients with known Gilbert's syndrome, ≤3 × ULN is permitted. ii. ALT or AST ≤3.0× ULN. c. Renal function: i. Serum/plasma creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min based on Cockcroft-Gault formula (for patients in France, serum/plasma creatinine ≤1.5 × ULN or CrCl ≥60 mL/min based on Cockcroft-Gault formula). d. Albumin ≥30 g/L.
  12. Human immunodeficiency virus-infected patients who are healthy and have a low risk of acquired immunodeficiency syndrome-related outcomes are included in this trial.
  13. For patients who have partners who are pregnant or of childbearing potential: a condom is required along with a highly effective contraceptive method during the study and for 6 months after last study drug administration. Such methods deemed highly effective include a) combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, b) progestogen-only hormonal contraception associated with inhibition of ovulation, c) intrauterine device (IUD), d) intrauterine hormone-releasing system (IUS), e) bilateral tubal occlusion, f) vasectomy, g) true sexual abstinence: 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 IMP, and withdrawal are not acceptable methods of abstinence].
  14. Willing to initiate ARAT therapy (either enzalutamide or abiraterone), pre-specified by investigator, if randomized to Treatment Arm B.
  15. ECOG performance status 0 to
  16. Willing and able to comply with all study requirements and treatments (including 177Lu PNT2002) as well as the timing and nature of required assessments.
  17. Signed informed consent.

Exclusion Criteria:

  • Patients are excluded from the study if any of the following criteria apply: 1. If noted in pathology report, prostate cancer with known significant (>10% present in cells) sarcomatoid or spindle cell or neuroendocrine components. Any small cell component in the cancer should result in exclusion. 2. Prior treatment for prostate cancer ≤28 days prior to randomization, with the exclusion of first-line local external beam, ARAT, luteinizing hormone-releasing hormone (LHRH) therapy, or non-radioactive bone-targeted agents. 3. Any prior cytotoxic chemotherapy for CRPC (e.g., cabazitaxel or docetaxel); chemotherapy for hormone-sensitive prostate cancer (HSPC) is allowed if the last dose was administered >1 year prior to consent. 4. Prior treatment with systemic radionuclides (e.g. radium-223, rhenium-186, strontium 89). 5. Prior immuno-therapy, except for sipuleucel-T. 6. Prior PSMA-targeted radioligand therapy, e.g., Lu-177-PSMA-617, I 131-1095. 7. Prior poly ADP ribose polymerase (PARP) inhibitor for prostate cancer. 8. Patients who progressed on 2 or more lines of ARATs. 9. Patients receiving bone-targeted therapy (e.g. denosumab, zoledronic acid) not on stable doses for at least 4 weeks prior to randomization. 10. Administration of an investigational agent ≤60 days or 5 half-lives, whichever is shorter, prior to randomization. 11. Major surgery ≤30 days prior to randomization. 12. Estimated life expectancy <6 months as assessed by the principal investigator. 13. Presence of liver metastases >1 cm on abdominal imaging. 14. A superscan on bone scan defined as a bone scan that demonstrates markedly increased skeletal radioisotope uptake relative to soft tissues in association with absent or faint genitourinary tract activity. 15. Dose escalation or initiation of opioids for cancer-related pain ≤30 days prior to consent up to and including randomization. 16. Known presence of central nervous system metastases. 17. Contraindications to the use of planned ARAT therapy, [Ga-68]-PSMA-11, [F-18]-DCFPyL or [Lu-177]-PNT2002 therapy, including but not limited to the following:
  • Hypersensitivity to [Ga-68]-PSMA-11, [F-18]-DCFPyL or [Lu-177]-PNT2002 excipients (Diethylenetriaminepentaacetic acid (DTPA), Sodium ascorbate, Lascorbic acid, Sodium gentisate, HCl, Sodium hydroxide).
  • Recent myocardial infarction or arterial thrombotic events (in the past 6 months) or unstable angina (in the past 3 months), bradycardia or left ventricular ejection fraction measurement of < 50%.
  • History of seizures in patients planned to receive enzalutamide. 18. Active malignancy other than low-grade non-muscle-invasive bladder cancer and non-melanoma skin cancer. 19. Concurrent illness that may jeopardize the patient's ability to undergo study procedures. 20. Serious psychological, familial, sociological, or geographical condition that might hamper compliance with the study protocol and follow-up schedule. Patients that travel need to be capable of repeated visits even if they are on the control arm. 21. Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression. 22. Concurrent serious (as determined by the investigator) medical conditions, including, but not limited to, New York Heart Association class III or IV congestive heart failure (see 12.1 Appendix 1), unstable ischemia, uncontrolled symptomatic arrhythmia, history of congenital prolonged QT syndrome, uncontrolled infection, known active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation.

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Changes in 18F-fluciclovine Positron Emission Tomography (PET) in Patients With Metastatic Castration Resistant Prostate Cancer Treated With With Life Prolonging Therapies: A Pilot Study


Condition: Metastatic Castration-resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04158245

Sponsor: Tulane University

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  1. Eastern Cooperative Oncology Group (ECOG) Performance status 0-2;
  2. Age ≥ 18 years;
  3. Histologically confirmed adenocarcinoma of the prostate;
  4. Ongoing use of luteinizing hormone-releasing hormone (LHRH) required in the absence of surgical castration and castrate concentration of testosterone (< 50 ng/dL);
  5. Detectable PSA of at least 2 ng/dL;
  6. Metastatic disease documented by CT or bone scan within 42 days of cycle 1 day 1;
  7. Life expectancy of ≥ 6 months;
  8. Must have disease progression despite a castrate concentration of testosterone of < 50 ng/dL based on: A. PSA progression defined as increase in PSA of at least 2 ng/dL and 25% from nadir values of prior therapy, determined by 2 separate measurement taken at least 1 week apart; And/or B. Radiographic disease progression based on response evaluation criteria in solid tumors (RECIST) 1.1 for soft tissue disease and/or prostate cancer working group 3 (PCWG3) for bone only disease;
  9. No prior life-prolonging therapies for mCRPC are allowed, except Sipuleucel-T;
  10. The use of docetaxel in the metastatic hormone-sensitive prostate cancer (mHSPC) setting is allowed;
  11. Low dose prednisone (10 mg or less) or equivalent is allowed;
  12. Acceptable liver function (within 28 days from enrollment) defined as: A. Bilirubin < 2.5 times upper limit of normal (ULN), except for patients with known Gilbert disease (in such cases bilirubin < 5 times ULN); B. AST (SGOT) and ALT (SGPT) < 3 times ULN
  13. Acceptable renal function (within 28 days from enrollment): A. Serum creatinine ≤ 2.0 x ULN or creatinine clearance ≥ 30 mL/min
  14. Acceptable hematologic status (within 28 days from enrollment): A. Absolute neutrophil count (ANC) ≥ 1000 cell/mm3 (100 x 109/L) B. Platelet count ≥ 100,000 platelet/mm3 (100 x 109/L) C. Hemoglobin ≥ 9 g/dL
  15. At least 2 weeks since prior radiation before starting study treatment (cycle 1 day 1);
  16. Able to understand and willing to sign a written informed consent document;
  17. Patients who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator and sponsor during the study and for 1 week after last dose of abiraterone acetate.

Exclusion Criteria:

  1. Pathological findings consistent with small cell carcinoma of the prostate;
  2. Prior treatment with docetaxel for metastatic castration-resistant prostate cancer (CRPC);
  3. Patient with normal 18F-flucicolovine PET/CT scans at baseline;
  4. Know allergies, hypersensitivity, or intolerance to abiraterone, prednisone, 18F-fluciclovine or their excipients;
  5. Any chronic medical condition requiring ≥ 10 mg daily of systemic prednisone (or equivalent);
  6. Major surgery (e.g., required general anesthesia) within 2 weeks before screening;
  7. Uncontrolled active infection (including hepatitis B or C or AIDS). Patients with hepatitis B/C who have disease under control and no significant liver function impairment, and undetectable viral load will be allowed to participate. Similarly, patients with known HIV and ≥ 400 CD4 + T cells are allowed to participate;
  8. Evidence of other metastatic malignancies within the last year;
  9. Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study.

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Phase I/II Dose-escalation Study of Fractionated and Multiple Dose 225Ac-J591 for Progressive Metastatic Castration Resistant Prostate Cancer


Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04506567

Sponsor: Weill Medical College of Cornell University

Phase: Phase 1/Phase 2

Eligibility:

  • Age: minimum 18 Years maximum 99 Years
  • Gender: Male

Inclusion Criteria:

  • 1. Histologically or cytologically confirmed adenocarcinoma of prostate 2. Documented progressive metastatic CRPC based on Prostate Cancer Working Group 3 (PCWG3) criteria, which includes at least one of the following criteria:
  • PSA progression
  • Objective radiographic progression in soft tissue
  • New bone lesions
  • ECOG performance status of 0-2 3. Have serum testosterone < 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone orchiectomy 4. Have previously been treated with at least one of the following in any disease state:
  • Androgen receptor signaling inhibitor (such as enzalutamide)
  • CYP 17 inhibitor (such as abiraterone acetate) 5. Have previously received taxane chemotherapy (in any disease state), been determined to be ineligible for taxane chemotherapy by their physician, or refused taxane chemotherapy. 6. Age > 18 years 7. Patients must have normal organ and marrow function as defined below:
  • Absolute neutrophil count >2,000 cells/mm3
  • Hemoglobin ≥9 g/dL
  • Platelet count >150,000 x 109/uL
  • Serum creatinine <1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault
  • Serum total bilirubin <1.5 x ULN (unless due to Gilbert's Syndrome in which case direct bilirubin must be normal)
  • Serum AST and ALT <3 x ULN in absence of liver metastases; < 5x ULN if due to liver metastases(in both circumstances bilirubin must meet entry criteria) 8. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  1. Implantation of investigational medical device ≤4 weeks of Treatment Visit 1 (Day 1) or current enrollment in oncologic investigational drug or device study
  2. Use of investigational drugs ≤4 weeks or <5 half-lives of Cycle 1, Day 1 or current enrollment in investigational oncology drug or device study
  3. Prior systemic beta-emitting bone-seeking radioisotopes
  4. Known active brain metastases or leptomeningeal disease
  5. History of deep vein thrombosis and/or pulmonary embolus within 1 month of C1D1
  6. Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or hematological organ systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study
  7. Radiation therapy for treatment of PC ≤4 weeks of Day 1 Cycle 1
  8. Patients on stable dose of bisphosphonates or denosumab, which have been started no less than 4 weeks prior to treatment start, may continue on this medication, however patients are not allowed to initiate bisphosphonate/Denosumab therapy during the DLT-assessment period of the study
  9. Having partners of childbearing potential and not willing to use a method of birth control deemed acceptable by the principle investigator and chairperson during the study and for 1 month after last study drug administration
  10. Currently active other malignancy other than non-melanoma skin cancer. Patients are considered not to have "currently active" malignancy if they have completed any necessary therapy and are considered by their physician to be at less than 30% risk of relapse
  11. Known history of known myelodysplastic syndrome

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Open-Label Phase 2 Study of Ladiratuzumab Vedotin (LV) for Unresectable Locally Advanced or Metastatic Solid Tumors


Condition: Small Cell Lung Cancer, Non-small Cell Lung Cancer, Squamous, Non-small Cell Lung Cancer, Non-squamous, Head and Neck Squamous Cell Carcinoma, Esophageal Squamous Cell Carcinoma, Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Prostate Cancer, Melanoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04032704

Sponsor: Seagen Inc.

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • All Cohorts
  • Measurable disease according to RECIST v1.1 as assessed by the investigator
  • Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1
  • Cohort 1: SCLC (Parts A and B)
  • Must have extensive stage disease
  • Must have disease progression during or following prior platinum-based systemic chemotherapy for extensive stage disease;
  • No more than 1 prior line of cytotoxic chemotherapy for extensive disease stage
  • May have received prior anti-PD(L)1 therapy
  • Cohort 2: NSCLC-squamous (Parts A and B)
  • Must have unresectable locally advanced or metastatic disease
  • Must have disease progression during or following systemic therapy
  • Participants must have progressed during or after a platinum-based combination therapy administered for the treatment of metastatic disease, OR
  • Participants must have progressed within 6 months of last dose of platinum-based adjuvant, neoadjuvant, or definitive chemotherapy, or concomitant chemoradiation regimen for early stage or locally advanced stage disease.
  • Participants with known epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), reactive oxygen species (ROS), BRAF, or other actionable mutations are not eligible
  • No more than 1 prior line of cytotoxic chemotherapy for their advanced disease
  • Must have received prior anti-PD(L)1 therapy, unless contraindicated
  • Cohort 3: NSCLC-nonsquamous (Parts A and B)
  • Must have unresectable locally advanced or metastatic disease
  • Must have disease progression during or following systemic therapy
  • Participants must have progressed during or after a platinum-based combination therapy administered for the treatment of metastatic disease, OR
  • Participants must have progressed within 6 months of last dose of platinum-based adjuvant, neoadjuvant, or definitive chemotherapy, or concomitant chemoradiation regimen for early stage or locally advanced state disease.
  • Participants with known EGFR, ALK, ROS, BRAF, tropomyosin receptor kinase (TRK), or other actionable mutations are not eligible
  • Must have had prior platinum-based chemotherapy
  • No more than 1 prior line of cytotoxic chemotherapy for their advanced disease
  • Must have received prior anti-PD(L)1 therapy, unless contraindicated
  • Cohort 4: HNSCC (Parts A and B)
  • Must have unresectable locally recurrent or metastatic disease
  • Must have disease progression during or following prior line of systemic therapy
  • Disease progression after treatment with a platinum-containing regimen for recurrent/metastatic disease; OR
  • Recurrence/progression within 6 months of last dose of platinum therapy given as part of a multimodal therapy in the curative setting
  • No more than 1 line of cytotoxic chemotherapy for their advanced disease
  • May have received prior anti-PD(L)1 therapy, unless contraindicated
  • Cohort 5: esophageal-squamous (Parts A and B)
  • Must have unresectable locally advanced or metastatic disease
  • Must have disease progression during or following systemic therapy
  • Must have had prior platinum-based chemotherapy
  • No more than 1 line of cytotoxic chemotherapy for their advanced disease
  • Cohort 6: gastric and GEJ adenocarcinoma (Parts A and B)
  • Must have unresectable locally advanced or metastatic disease
  • Must have received prior platinum-based therapy
  • Must have disease progression during or following systemic therapy
  • Participants with known human epidermal growth factor receptor 2 (HER2) overexpression must have received prior HER2-targeted therapy
  • No more than 1 line of prior cytotoxic chemotherapy for their advanced disease
  • Participants may have received prior anti-PD(L)1 therapy, unless contraindicated
  • Cohort 7: CRPC (Part B only)
  • Must have histologically or cytologically confirmed adenocarcinoma of the prostate
  • Participants with components of small cell of neuroendocrine histology are excluded
  • Must have metastatic castration-resistant disease
  • Must have been ≥28 days between cessation of androgen receptor-targeted therapy and start of study treatment
  • Must have received no more than 1 prior line of androgen receptor-targeted therapy for metastatic castration-sensitive prostate cancer or CRPC
  • No prior cytotoxic chemotherapy in the metastatic CRPC setting
  • For participants who received cytotoxic chemotherapy in CSPC, at least 6 months must have elapsed between last dose of chemotherapy and start of study treatment
  • No more than 1 prior line of cytotoxic chemotherapy for CSPC
  • Participants with measurable disease are eligible if the following criteria are met:
  • A minimum starting PSA level ≥1.0 ng/mL
  • Participants with measurable soft tissue disease must have evidence of measurable soft tissue disease according to PCWG3 criteria.
  • Participants with known breast cancer gene (BRCA) mutations are excluded
  • No prior radioisotope therapy or radiotherapy to ≥30% of bone marrow
  • Cohort 8: Melanoma (Parts B and C)
  • Must have histologically or cytologically confirmed cutaneous malignant melanoma
  • Participants with mucosal, acral, or uveal melanoma are excluded
  • Must have locally advanced unresectable or metastatic stage disease
  • Must have progressive disease following anti-PD(L)1 therapy
  • Must have received BRAF +/- MEK inhibitor therapy if BRAF mutated (Part C)

Exclusion Criteria:

  • Active concurrent malignancy or a previous malignancy within the past 3 years
  • Any anticancer therapy within 3 weeks of starting study treatment. Participants who are/were on adjuvant hormonal therapy for the treatment of malignancies with negligible risk of metastases are eligible.
  • Known active central nervous system lesions
  • Any ongoing clinically significant toxicity associated with prior treatment (Grade 2 or higher)
  • Ongoing sensory or motor neuropathy of Grade ≥2
  • Has received prior radiotherapy within 2 weeks of start of study treatment
  • History of interstitial lung disease.

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ENZA-p: A Randomised Phase II Trial Using PSMA as a Therapeutic Agent and Prognostic Indicator in Men With Metastatic Castration-resistant Prostate Cancer Treated With Enzalutamide (ANZUP 1901)


Condition: Metastatic Castration-Resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04419402

Sponsor: Australian and New Zealand Urogenital and Prostate Cancer Trials Group

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • 1. Males aged 18 or older with metastatic adenocarcinoma of the prostate defined by:
  • Documented histopathology of prostate adenocarcinoma (no features of neuroendocrine carcinoma) OR
  • Metastatic disease typical of prostate cancer 2. Castration-resistant prostate cancer (defined as disease progressing despite castration by orchiectomy or ongoing luteinising hormone-releasing hormone agonist or antagonist). 3. Progressive disease with rising PSA defined by PCWG3 criteria (sequence of 2 rising values at a minimum of 1-week intervals) AND PSA ≥ 5 ng/mL. 4. At least 2 of the following risk factors for early treatment failure with enzalutamide:
  • LDH ≥ ULN
  • ALP ≥ ULN
  • Albumin <35 g/L
  • De novo metastatic disease (M1) at initial diagnosis *
  • <3 years since initial diagnosis
  • >5 bone metastases *
  • Visceral metastases *
  • PSA doubling time <84 days
  • Pain requiring opiates for >14 days
  • Prior treatment with abiraterone * Based on conventional imaging (CT and/or bone scan) 5. Target or non-target lesions according to RECIST 1.1 6. Significant PSMA avidity on 68Ga-PSMA PET/CT, defined as SUVmax >15 at a single site (regardless of lesion size) and SUV max >10 at sites of disease ≥10mm (unless subject to factors explaining a lower uptake, e.g. respiratory motion, reconstruction artefact) 7. ECOG performance status 0-2 8. Adequate renal function:
  • Creatinine clearance ≥ 40mL/ min 9. Adequate liver function:
  • Bilirubin < 1.5 x upper limit of normal (ULN) (or if bilirubin is between 1.5 - 2x ULN, must have a normal conjugated bilirubin)
  • AST or ALT ≤ 2.0 x ULN (or ≤ 5.0 x ULN in the presence of liver metastases) 10. Adequate bone marrow function:
  • Platelets ≥ 100 x109/L
  • Haemoglobin ≥ 90g/L (no red blood cell transfusion in last 4 weeks)
  • Neutrophils > 1.5 x109/L 11. Estimated life expectancy > 12 weeks 12. Study treatment both planned and able to start within 21 days of randomisation 13. Willing and able to comply with all study requirements (including both treatments: enzalutamide and Lu-PSMA), and all required study assessments 14. Signed, written, informed consent

Exclusion Criteria:

  1. Prostate cancer with known significant sarcomatoid, or spindle cell, or neuroendocrine small cell components, or metastasis of other cancer to the prostate
  2. 68Ga-PSMA PET/CT SUVmax < 10 at a site of measurable disease > 10mm
  3. Prior treatment with enzalutamide, darolutamide, or apalutamide. Prior treatment with abiraterone is allowed.
  4. Prior treatment with any PSMA-targeted radiotherapy
  5. Prior chemotherapy for mCRPC. Prior docetaxel in castration-sensitive setting is permitted
  6. History of another malignancy within 5 years prior to randomisation except for non-melanomatous carcinoma of the skin; or, adequately treated, non-muscle-invasive urothelial carcinoma of the bladder (i.e. Tis, Ta and low grade T1 tumours)
  7. Concurrent illness, including severe infection that may jeopardise the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety
  8. 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
  9. Men in sexual relationships with women of reproductive potential who are not willing/able to use medically acceptable forms of barrier contraception
  10. History of:
  11. seizure or any condition that may predispose to seizure (e.g. prior cortical stroke or significant brain trauma)
  12. loss of consciousness or transient ischemic attack within 12 months of randomization
  13. significant cardiovascular disease within the last 3 months: including myocardial infarction, unstable angina, congestive heart failure (NYHA grade II or greater, see Appendix 4), ongoing arrhythmias of Grade > 2, thromboembolic events (e.g. deep vein thrombosis, pulmonary embolism). Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed

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Prostate Cancer Biomarker Enrichment and Treatment Selection (PC-BETS) Study


Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03385655

Sponsor: Canadian Cancer Trials Group

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • The following will be required prior to REGISTRATION:
  • Patients must have histologically confirmed adenocarcinoma of the prostate without pathologic or clinical evidence (e.g. PSA < 2.0 μg/L with liver metastases) of small cell neuroendocrine differentiation.
  • Patients must consent prior to blood collection for screening correlative testing by a central reference laboratory. The screening blood sample cannot be sent for analysis prior to screening registration.
  • All patients must have consented to the release of a tumour block from their primary or metastatic tumour. The centre/pathologist must have agreed to the submission of the specimen(s). Contact CCTG if no archival tissue is available.
  • Patients must have evidence of castrate resistance with either biochemical or radiological disease progression in the setting of surgical or medical castration: PSA Progression:
  • Minimum of two rising PSA values from a baseline measurement with an interval of ≥ 1 week between each measurement
  • PSA must be ≥ 2.0 µg/L (ng/mL) Objective progression:
  • RECIST 1.1, or
  • PCWG3 Criteria for bone progression Surgical/Medical Castration:
  • Prior bilateral orchiectomy, or
  • LHRH agonist/antagonist and testosterone < 50 ng/dL or < 1.7 nmol/L. LHRH agonist/antagonist therapy must be maintained for the duration of study therapy and if previously discontinued, must be restarted and castrate level of testosterone present.
  • Patients must be ≥18 years of age.
  • ECOG performance status 0 or 1 (Appendix I) and have a life expectancy of ≥ 6 months.
  • Patients must have radiologically documented disease (measurable or non-measurable as defined by RECIST 1.1. Patients with elevated PSA only are not eligible.
  • Neutrophils ≥ 1.5 x 10^9/L
  • Platelets ≥ 100 x 10^9/L
  • Hemoglobin ≥ 90 g/L; contact CCTG if hemoglobin is between 80-89 g/L, patient is not decompensated, is asymptomatic and transfusion is not indicated.
  • Serum potassium within normal limits
  • Bilirubin ≤ 1.5 ULN; if confirmed Gilbert's then bilirubin ≤ 3.0 x ULN
  • ALT ≤ 2.5 x ULN; if patient has liver metastases ≤ 5.0 x ULN
  • Serum creatinine ≤ 1.5 x ULN or Creatinine clearance ≥ 45 mL/min; measured directly by 24-hour urine sampling OR as calculated by Cockcroft and Gault equation: Males: GFR = 1.23 x (140-age) x weight in kg/serum creatinine in μmol/L
  • Patient consent for screening and subsequent enrollment (as applicable) must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to screening and subsequent enrollment (as applicable) in the trial to document their willingness to participate. Additional Criteria to be met prior to SUB-STUDY ENROLLMENT:
  • Patients must have recovered from any treatment-related toxicities prior to enrollment (unless ≤ grade 1, irreversible, or considered by investigator as not clinically significant).
  • Prior major surgery is permitted provided that a minimum of 14 days have elapsed between any major surgery and enrollment (7 days for minor surgery e.g. port insertion), and that wound healing has occurred.
  • Prior external beam radiation or radium-223 is permitted provided a minimum of 28 days (4 weeks) have elapsed between the last dose and enrollment. Consult CCTG if patients have received other therapeutic radioisotopes. Exceptions may be made for low-dose non-myelosuppressive radiotherapy after consultation with CCTG. Concurrent radiation is not permitted. If radiation is required for example for pain control, it must be completed prior to enrollment. Prior strontium-89 at any time is not permitted.
  • Previous Hormone Therapy: Patients must have received prior hormonal treatment with at least one of: abiraterone acetate, enzalutamide, apalutamide (ARN-509), darolutamide (ODM-201), TAK-700 and TOK-001 or other next-generation AR-pathway inhibitor (if agent is not listed, must be discussed and approved with CCTG prior to registration). Consult substudies for additional criteria
  • Prior cytotoxic therapy: Patients may have received cytotoxic therapy in the castrate sensitive setting as well as up to 1 regimen of cytotoxic therapy in the CRPC setting
  • Patients must have an adequate washout prior to enrollment as follows:
  • Longest of one of the following:
  • Standard cycle length of standard therapies;
  • Two weeks;
  • The longer of 30 days or 5 half-lives for investigational agents;
  • Patients must have discontinued anti-androgens for at least 4 weeks prior to substudy entry/enrollment (at least 6 weeks for bicalutamide).
  • LHRH agonist therapy must continue unless surgically castrated. Note: after discussion, CCTG selected patients may be screened prior to adequate washout.
  • Patient must have progressed (biochemically or radiologically, as defined in 4.1.4) during or after their last systemic therapy
  • Patients must be accessible for treatment and follow up. Patients registered enrolled on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits (for example: 1 ½ hour's driving distance) placed on patients being considered for this trial.
  • Investigators must assure themselves the patients enrolled on this trial will be available for complete documentation of the treatment, adverse events, response assessment and follow-up.
  • Patients must agree to return to their primary care facility for any adverse events, which may occur through the course of the trial.
  • In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient enrollment.
  • Men of childbearing potential must have agreed to use a highly effective contraceptive method during study drug treatment for 6 months after stopping treatment and should not father a child or donate sperm during this period.
  • In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation, or vasectomy / vasectomized partner. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he is responsible for beginning contraceptive measures.

Exclusion Criteria:

  • Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, or other solid tumours curatively treated with no evidence of disease for ≥ 2 years.
  • Patients with central nervous system (CNS) involvement unless at least 4 weeks from prior therapy completion (including radiation and/or surgery) AND clinically stable and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases. Patients with epilepsy not due to CNS metastases are eligible as long as no contraindication or concern with drug interactions.
  • Patients with serious illnesses or medical conditions which could cause unacceptable safety risks or would not permit the patient to be managed according to the protocol. This includes but is not limited to:
  • active infection requiring systemic therapy;
  • active or known human immunodeficiency virus (HIV) with detectable viral load;
  • uncontrolled or recent clinically significant cardiac disease, including:
  • angina pectoris, symptomatic pericarditis, coronary artery bypass grafting, coronary angioplasty, or stenting, or myocardial infarction in the previous 12 months;
  • history of documented congestive heart failure (New York Heart Association functional classification III-IV) or cardiomyopathy;
  • history of any cardiac arrhythmias, e.g. ventricular, supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months;
  • patients with uncontrolled hypertension.
  • Patients with significant liver diseases including viral/other hepatitis, current alcohol abuse or cirrhosis.
  • Patients who are unable to swallow oral medication and/or have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g. Crohn's disease, ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, active bowel inflammation (e.g. diverticulitis) or small bowel resection), unless agreed with CCTG (exceptions may be given if parenteral substudy is available/appropriate.
  • Patients who require continued or concurrent treatment with:
  • Systemic corticosteroids at a dose equivalent to prednisone > 10 mg daily. Topical applications (e.g. rash), inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intra-articular) are allowed.
  • Bisphosphonates / denosumab for reasons other than hypercalcemia, osteoporosis or prevention of skeletal-related events.
  • Other anti-cancer or investigational agents (except LHRH)
  • History of hypersensitivity to any of the study drugs or any excipient.
  • Patients with a history of non-compliance to medical regimens.
  • Patients who have received growth factors within 28 days prior to initiation of dosing of study drug or who are likely to require treatment with growth factors throughout the duration of the trial.

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A Randomized Phase II Trial to Evaluate the Antitumor Activity of Enzalutamide and Talazoparib (PF-06944076) for the Treatment of Metastatic Hormone-naïve Prostate Cancer


Condition: Metastatic Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04332744

Sponsor: MedSIR

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  1. Adult patients (>18 y.o.) who signed informed consent form (ICF) prior to participation in any study-related activities.
  2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
  4. High-volume metastatic disease documented on bone scan or computed tomography (CT)/magnetic resonance imaging (MRI) scan, defined as the presence of either visceral disease and/or at least four bone metastases on bone scan, with at least one of them beyond spine/pelvis.
  5. Life expectancy of ≥ 12 months.
  6. Histologically confirmed adenocarcinoma of the prostate without predominance of small-cell or neuroendocrine features according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines based on local testing on the most recent analyzed biopsy. Note: Central confirmation of adenocarcinoma is not required for study entry. However, tissue blocks, or slides, must be submitted to confirm the diagnoses by a Sponsor-designated central laboratory retrospectively and/or exploratory biomarker analyses.
  7. Willingness and ability to provide tumor paired biopsies during the study participation in order to perform exploratory studies. At the study entry, the most recent tumor biopsy since last progression from either metastatic or primary tissues will be provided. If not feasible, patient eligibility should be evaluated by a Sponsor's qualified designee.
  8. Adequate hematologic and organ function within 28 days before the first study treatment on Cycle 1 Day 1, defined by the following:
  9. Hematological: White blood cell (WBC) count > 3.0 x 109/L; Absolute neutrophil count (ANC) > 1.5 x 109/L; Platelet count > 100.0 x109/L; Hemoglobin (Hb) > 9.0 g/dL. Note: Patients receiving growth factors or blood transfusions within 14 days before obtaining the hematology values at screening will be excluded.
  10. Hepatic: Total bilirubin ≤ 1.5 times the upper limit of normal (× ULN) (≤ 3 x ULN in the case of Gilbert's disease); Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN (in the case of liver metastases ≤ 5 × ULN); Alkaline phosphatase (ALP) ≤ 2.5 × ULN (≤ 5 × ULN inthe case of liver and/or bone metastases).
  11. Renal: Serum creatinine < 1.5 × ULN or creatinine clearance ≥ 30 mL/min based on Cockcroft-Gault glomerular filtration rate estimation.
  12. Coagulation: International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless on medication known to alter INR and/or aPTT.
  13. Nutritional status: Serum Albumin ≥ 2.8 g/dL.
  14. Bisphosphonates or denosumab dosage must have been stable for at least 4 weeks before Day 1 for patients receiving these therapies.
  15. Patients must agree to use a condom when is engaged in sexual activity with a pregnant woman during the treatment period and for at least 90 days after last dose of enzalutamide or at least 120 days after last dose of talazoparib (PF-06944076), whichever occurs later. Patients must also agree to use an additional highly effective form of contraception or two effective contraceptive methods, when is engaged in sexual intercourse with a woman of childbearing potential during the treatment period and for at least 90 days after last dose of enzalutamide or at least 120 days after last dose of talazoparib (PF-06944076), whichever occurs later.
  16. Must agree to refrain to donate sperm during the treatment period and for at least 90 days after last dose of enzalutamide or at least 120 days after last dose of talazoparib (PF-06944076), whichever occurs later.
  17. PSA ≥ 4 ng/mL at diagnosis or before starting ADT therapy.

Exclusion Criteria:

  1. Prior treatment with enzalutamide, apalutamide, darolutamide or abiraterone acetate.
  2. History of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills.
  3. Known hypersensitivity to recombinant proteins, or any excipient contained in the drug formulation for talazoparib (PF-06944076) and enzalutamide.
  4. Prior systemic therapy for metastatic prostate cancer (mPCa). Note: Initiation of androgen deprivation therapy (ADT) within 4 weeks prior to study entry would be allowed (with or without first-generation antiandrogens), providing a tumor biopsy sample was taken prior to initiation of ADT is made available for biomarker studies and upon approval by the sponsor. If patient was started on first-generation antiandrogens, these would be discontinued on prior to randomization. Note: Patients relapsing after having received an ADT-based regimen in neoadjuvant or adjuvant setting will be suitable for the study if metastatic progression occured while on non-castrate testosterone levels or at least 12 months after discontinuation of ADT.
  5. Treatment with approved or investigational cancer therapy within 28 days (or 5 half-lives of the drug- whichever is longer) prior to initiation of study treatment.
  6. Known or suspected brain metastases or active leptomeningeal disease.
  7. Symptomatic or impending spinal cord compression or cauda equina syndrome.
  8. Subject has a history of seizure or any condition that may predispose to seizure (i.e. prior significant brain trauma, brain vascular malformations, ...), or subjects that have had unexplained loss of consciousness or transient ischemic attacks within 1 year prior to scheduled Day 1 of treatment.
  9. Therapeutic radiation therapy within 14 days (seven days for limited-field palliative radiotherapy) prior to study enrolment, or patients who have not recovered from radiotherapy-related toxicities to grade ≤ 1 according to National Cancer Insitute ́s Common Terminology Criteria for Adverse Events (NCI-CTCAE) version (v.)5.
  10. Major surgery (defined as requiring general anesthesia) or significant traumatic injury within 14 days of start of study drugs, or patients who have not recovered from the side effects of any major surgery.
  11. History of another malignancy within three years of study enrollment with the exception of carcinoma in situ, non-melanoma skin carcinoma, or American Joint Committee on Cancer stage 0 or stage 1 cancer that has a remote probability of recurrence in the opinion of the investigator and the Sponsor's Medical Monitor is required, or any concurrent malignancy for which the patient is receiving therapy.
  12. Active uncontrolled infection at the time of enrollment.
  13. Congenital long QT syndrome or Electrocardiogram (ECG) at screening with QT interval corrected using Fridericia's formula (QTcF) > 500 milliseconds.
  14. Patients with clinically significant cardiovascular disease including but not limited to any of the following:
  15. Stroke, transient ischemic attack, unstable angina pectoris, or documented myocardial infarction within 12 months prior to study entry.
  16. Symptomatic pericarditis or clinically significant pericardial effusion or myocarditis.
  17. Documented congestive heart failure (New York Heart Association functional classification III- IV).
  18. Uncontrolled, persistent hypertension defined as systolic blood pressure > 170 mmHg or diastolic blood pressure > 100 mmHg.
  19. Patients have any of the following cardiac conduction abnormalities:
  20. Ventricular arrhythmias except for benign premature ventricular contractions.
  21. Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication.
  22. Conduction abnormality requiring a pacemaker.
  23. Other cardiac arrhythmia not controlled with medication.
  24. Patients have any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator's judgment contraindicate patient participation in the clinical study.
  25. Treatment with estrogens, cyprotoerone acetate or glucocorticoids (at a dose greater than the equivalent to 10 mg/day of prednisone) in the 4 weeks prior to scheduled Day 1 of treatment.
  26. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are employees of the trial sponsor, including their family members, directly involved in the conduct of the study.
  27. Concurrent participation in other clinical trial, except other translational studies or observational studies (defined as those with no therapeutic intervention).

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A Phase 1/2 Study of REGN5678 (Anti-PSMAxCD28) With Cemiplimab (Anti-PD-1) in Patients With Metastatic Castration-resistant Prostate Cancer


Condition: Metastatic Castration-resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03972657

Sponsor: Regeneron Pharmaceuticals

Phase: Phase 1/Phase 2

Eligibility:

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

Key Inclusion Criteria:

  • Histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma
  • Metastatic, castration-resistant prostate cancer (mCRPC) with PSA value at screening ≥4 ng/mLthat has progressed within 6 months prior to screening as defined in the protocol
  • Has received ≥2 lines prior systemic therapy approved in the metastatic and/or castration-resistant setting (in addition to androgen deprivation therapy [ADT]) including at least one second-generation anti-androgen therapy (eg, abiraterone, enzalutamide, apalutamide, or darolutamide)

Key Exclusion Criteria:

  • Has received treatment with an approved systemic therapy within 3 weeks of dosing or has not yet recovered (ie, grade ≤1 or baseline) from any acute toxicities
  • Has received any previous systemic biologic therapy within 5 half-lives of first dose of study therapy
  • Has received prior PSMA-targeting therapy
  • Dose Expansion Only: Has had prior anti-cancer immunotherapy
  • Any condition that requires ongoing/continuous corticosteroid therapy (>10 mg prednisone/day or anti-inflammatory equivalent) within 1 week prior to the first dose of study therapy
  • Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments
  • Encephalitis, meningitis, neurodegenerative disease (with the exception of mild dementia that does not interfere with activities of daily living [ADLs]) or uncontrolled seizures in the year prior to first dose of study therapy
  • Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection; or diagnosis of immunodeficiency NOTE: Other protocol defined Inclusion/

Exclusion Criteria:

  1. apply

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Androgen Deprivation Therapy for Oligo-recurrent Prostate Cancer in Addition to radioTherapy


Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04302454

Sponsor: University Medical Center Groningen

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  1. Histologically proven initial diagnosis of adenocarcinoma of the Prostate.
  2. Biochemical recurrence of prostate cancer following primary local prostate treatment (radical prostatectomy, primary radiotherapy or radical prostatectomy +/- prostate bed adjuvant salvage radiotherapy) according to the EAU guidelines 20
  3. BCR after surgery: PSA > 0.1ng/ml. BCR after radiotherapy: PSA nadir +2 ng/ml or 3 consequent rises in PSA level (after exclusion of possible bounce effect).
  4. Minimal 1 lesion and maximum 4 lesions (bone + lymph nodes) in total, without evidence of visceral metastases.
  5. Nodal relapse (N1) in the pelvis on PSMA-PET/CT with a maximum of 4 positive lymph nodes. The upper limit of the pelvis is defined as the aortic bifurcation.
  6. Nodal relapse (M1a) on PSMA-PET/CT above the aortic bifurcation with a maximum of 3 positive lymph nodes.
  7. Bone relapse on PSMA-PET/CT with a maximum of 3 lesions.
  8. Combination of a, b, c with a maximum of 4 metastases.
  9. Age > 18 years.
  10. Recent PSMA-PET/CT scan within 60 days prior to randomization.
  11. PSA < 10 ng/ml.
  12. In case of chronic use of finasteride the PSA value should be < 5 ng/ml.
  13. WHO performance state 0-
  14. Signed informed consent prior to registration/randomization.

Exclusion Criteria:

  1. Visceral metastases.
  2. PSA ≥ 10 ng/ml.
  3. PSA-doubling time ≤ 3 months.
  4. ADT or chemotherapy for recurrent PCa.
  5. Testosterone < 1.7 nmol/l
  6. Painful metastases needed pain medication (> level 1 pain medication) .
  7. Invasive active cancers other than superficial non-melanoma skin cancers.
  8. Inability or unwillingness to understand the information on trial-related topics, to give informed consent or to fill out QoL questionnaires.

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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 hormone-sensitive prostate adenocarcinoma without small-cell tumours diagnosed within 180 days of randomisation
  • 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 93 days 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:

  • Prior radical prostatectomy or definitive radiotherapy with therapeutic intent for prostate cancer. Palliative radiotherapy is allowed providing any wide field radiation therapy is completed more than 4 weeks before randomisation
  • 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 significantly 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. Symptomatic hypotension
  • systolic blood pressure (SBP) <90 mmHg and/or diastolic blood pressure (DBP) <50 mmHg vii. Cardiac ejection fraction below the 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 clearance < 50 mL/min (measured or calculated by Cockcroft and Gault equation)
  • 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 with a narrow therapeutic window within 1 week before the start of study treatment
  • Drugs known to significantly 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 Participants 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 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
  • Prior treatment with second generation anti-androgens (example, enzalutamide)
  • 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.

View trial on ClinicalTrials.gov


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