Prostate Cancer

{{header-clinical-trials-navigation}}

PSMAfore: A Phase III, Open-label, Multi-Center, Randomized Study Comparing 177Lu-PSMA-617 vs. a Change of Androgen Receptor-directed Therapy in the Treatment of Taxane Naïve Men With Progressive Metastatic Castrate Resistant Prostate Cancer


Condition: Prostatic Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04689828

Sponsor: Novartis Pharmaceuticals

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • Participants eligible for inclusion in this study must meet all of the following criteria: 1. Signed informed consent must be obtained prior to participation in the study 2. Participants must be adults ≥ 18 years of age 3. Participants must have an ECOG performance status of 0 to 1 4. Participants must have histological pathological, and/or cytological confirmation of adenocarcinoma of the prostate 5. Participants must be 68Ga-PSMA-11 PET/CT scan positive, and eligible as determined by the sponsor's central reader 6. Participants must have a castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L) 7. Participants must have progressed only once on prior second generation ARDT (abiraterone, enzalutamide, darolutamide, or apalutamide)
  • first generation androgen receptor inhibitor therapy (e.g. bicalutamide) is allowed but not considered as prior AEDT therapy
  • second generation ARDT must be the most recent therapy received 8. Participants must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria:
  • Serum/plasma PSA progression defined as 2 increases in PSA measured at least 1 week apart. The minimal start value is 2.0 ng/mL. 1.0 ng/ml is the minimal starting value if confirmed rise in PSA is the only indication of progression.
  • Soft-tissue progression defined [PCWG3-modified RECIST v1.1 (Eisenhauer et al 2009, Scher et al 2016)]
  • Progression of bone disease two new lesions only positivity on the bone scan defines metastatic disease to bone (PCWG3 criteria (Scher et al 2016)) 9. Participants must have ≥ 1 metastatic lesion that is present on screening/baseline CT, MRI, or bone scan imaging obtained prior to randomization. 10. Participants must have recovered to ≤ Grade 2 from all clinically significant toxicities related to prior therapies (i.e. prior chemotherapy, radiation, etc.) except alopecia 11. Participants must have adequate organ function:
  • Bone marrow reserve:
  • ANC ≥ 1.5 x 109/L
  • Platelets ≥100 x 109/L
  • Hemoglobin ≥ 9 g/dL
  • Hepatic:
  • Total bilirubin < 2 x the institutional upper limit of normal (ULN). For participants with known Gilbert's Syndrome ≤ 3 x ULN is permitted
  • ALT or AST ≤ 3.0 x ULN OR ≤ 5.0 x ULN for participants with liver metastases
  • Renal:
  • eGFR ≥ 50 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) equation 12. Albumin ≥ 2.5 g/dL 13. Candidates for change in ARDT as assessed by the treating physician • Participants cannot have previously progressed nor had intolerable toxicity to both enzalutamide and abiraterone.

Exclusion Criteria:

  • Participants meeting any of the following criteria are not eligible for inclusion in this study: 1. Previous treatment with any of the following within 6 months of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation 2. Previous PSMA-targeted radioligand therapy 3. Prior treatment with PARP inhibitors, cytotoxic chemotherapy for castration resistant or castrate sensitive prostate cancer (e.g., taxanes, platinum, estramustine, vincristine, methotrexate, etc.), immunotherapy or biological therapy [including monoclonal antibodies]) [Note: Taxane exposure (maximum 6 cycles) in the adjuvant or neoadjuvant setting is allowed if 12 months have elapsed since completion of this adjuvant or neoadjuvant therapy]. Prior treatment with sipuleucel-T is allowed. 4. Any investigational agents within 28 days prior to day of randomization 5. Known hypersensitivity to any of the study treatments or its excipients or to drugs of similar classes 6. Concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological therapy, or investigational therapy 7. Transfusion or use of bone marrow stimulating agents for the sole purpose of making a participant eligible for study inclusion 8. Patients with a history of CNS metastases that are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. Participants with CNS metastases are eligible if received therapy (surgery, radiotherapy, gamma knife), asymptomatic and neurologically stable without corticosteroids. Participants with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired. 9. Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression 10. History or current diagnosis of the following ECG abnormalities indicating significant risk of safety for study participants:
  • Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block)
  • History of familial long QT syndrome or known family history of Torsades de Pointe
  • Cardiac or cardiac repolarization abnormality, including any of the following: History of myocardial infarction (MI), angina pectoris, or CABG within 6 months prior to starting study treatment 11. Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to New York Heart Association class III or IV congestive heart failure, 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
  • HIV-infected participants who are at a low risk of AIDS-related outcomes may participate in this trial.
  • Participants with an active documented COVID-19 infection (any grade of disease severity) at time of informed consent may be included only when completely recovered (in accordance with local guidance). 12. Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. Participants with a prior history of malignancy that has been adequately treated and who have been disease free for more than 3 years prior to randomization are eligible, as are participants with adequately treated non-melanoma skin cancer and superficial bladder cancer 13. Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 14 weeks after stopping study treatment. A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants must not donate sperm for the time period specified above. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF 14. Unmanageable concurrent bladder outflow obstruction or urinary incontinence. Note: Participants with bladder outflow obstruction or urinary incontinence, which is manageable and controlled with best available standard of care (incl. pads, drainage) are allowed. 15. History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study 16. Any condition that precludes raised arms position 17. Presence of any mutations or biomarkers that are known to as predictors of better response to treatments other than ARDT (e.g., AR-V7 or BRCA) 18. Not able to understand and to comply with study instructions and requirements

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

UpFrontPSMA : A Randomised Phase 2 Study of Sequential 177Lu-PSMA617 and Docetaxel Versus Docetaxel in Metastatic Hormone-Naive Prostate Cancer


Condition: Metastatic Hormone Naive Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04343885

Sponsor: Peter MacCallum Cancer Centre, Australia

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • for study registration: 1. Patient has provided written informed consent 2. Male aged 18 years or older at screening 3. Prostate cancer diagnosed within 12 weeks of commencement of screening 4. Histologically or cytologically confirmed adenocarcinoma of the prostate without significant neuroendocrine differentiation or small cell histology OR metastatic disease typical of prostate cancer (i.e. involving bone or pelvic lymph nodes or para-aortic lymph nodes) with a rising serum PSA 5. Evidence of metastatic disease on CT and/or bone scan 6. PSA > 10ng/ml prior to commencement of medical ADT or surgical orchidectomy 7. Adequate haematological, renal and hepatic functions as defined by:
  • Absolute neutrophil count >1.5 x 109/L
  • Platelet count >100 x 109/L
  • Haemoglobin ≥ 90g/L (no red blood cell transfusion in 4 weeks prior to randomisation)
  • Creatinine Clearance ≥ 40mL/min (Cockcroft-Gault formula)
  • Total bilirubin < 1.5 x ULN (unless known or suspected Gilbert syndrome)
  • Aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 2.0 x ULN (or ≤ 5.0 x ULN in the presence of liver metastases) 8. Have a performance status of 0-2 on the ECOG Performance Scale (see Appendix 1) 9. Life expectancy greater than 6 months with treatment 10. Assessed by a medical oncologist as suitable for treatment with docetaxel 11. Patients must agree to use an adequate method of contraception 12. Willing and able to comply with all study requirements, including all treatments and required assessments including follow-up Exclusion Criteria for Registration: 1. Any prior pharmacotherapy, radiation therapy, or surgery for metastatic prostate cancer. The following exceptions are permitted:
  • Up to 4 weeks of ADT with luteinising hormone releasing hormone agonists or antagonists or orchiectomy ± concurrent anti-androgens are permitted prior to commencement of screening. At investigator discretion, patients may start ADT at commencement of protocol therapy
  • Up to one course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered at least 14 days prior to registration 2. Symptomatic cord compression, or clinical or imaging findings concerning for impending cord compression 3. Central nervous system metastases 4. Patients with Sjogren's syndrome 5. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator 6. Prior diagnosis of another cancer that was:
  • More than 3 years prior to current diagnosis with subsequent evidence of disease recurrence or clinical expectation of recurrence greater than 10%
  • Within 3 years of current diagnosis with the exception of successfully treated basal cell or squamous cell skin carcinoma or adequately treated non-muscle invasive bladder cancer (Tis, Ta and low grade T1 tumours) Inclusion Criteria for Randomisation: 1. Significant PSMA avidity on 68Ga-PSMA PET/CT, defined after central review as a minimum uptake of SUVmax 15 at a site of disease 2. High-volume metastatic disease on 68Ga-PSMA PET/CT defined as visceral metastases or ≥ 4 bone metastases with ≥ 1 outside the vertebral column and pelvis (extra-axial skeleton) 3. Patient continues to meet all the inclusion criteria for registration Exclusion Criteria for Randomisation: 1. Major FDG-PET discordance defined as presence of FDG positive disease with minimal PSMA expression in multiple sites (>5) or in more than 50% of total disease volume 2. All the

Exclusion Criteria:

  • for Registration: 1. Any prior pharmacotherapy, radiation therapy, or surgery for metastatic prostate cancer. The following exceptions are permitted:
  • Up to 4 weeks of ADT with luteinising hormone releasing hormone agonists or antagonists or orchiectomy ± concurrent anti-androgens are permitted prior to commencement of screening. At investigator discretion, patients may start ADT at commencement of protocol therapy
  • Up to one course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered at least 14 days prior to registration 2. Symptomatic cord compression, or clinical or imaging findings concerning for impending cord compression 3. Central nervous system metastases 4. Patients with Sjogren's syndrome 5. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator 6. Prior diagnosis of another cancer that was:
  • More than 3 years prior to current diagnosis with subsequent evidence of disease recurrence or clinical expectation of recurrence greater than 10%
  • Within 3 years of current diagnosis with the exception of successfully treated basal cell or squamous cell skin carcinoma or adequately treated non-muscle invasive bladder cancer (Tis, Ta and low grade T1 tumours) Inclusion Criteria for Randomisation: 1. Significant PSMA avidity on 68Ga-PSMA PET/CT, defined after central review as a minimum uptake of SUVmax 15 at a site of disease 2. High-volume metastatic disease on 68Ga-PSMA PET/CT defined as visceral metastases or ≥ 4 bone metastases with ≥ 1 outside the vertebral column and pelvis (extra-axial skeleton) 3. Patient continues to meet all the inclusion criteria for registration Exclusion Criteria for Randomisation: 1. Major FDG-PET discordance defined as presence of FDG positive disease with minimal PSMA expression in multiple sites (>5) or in more than 50% of total disease volume 2. All the exclusion criteria for registration continue to not apply

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

A Phase 3 Randomized, Placebo-controlled, Double-blind Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for the Treatment of Participants With Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-Mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC)


Condition: Metastatic Castrate Sensitive Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04497844

Sponsor: Janssen Research & Development, LLC

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • Pathological diagnosis of prostate adenocarcinoma
  • Must have appropriate deleterious homologous recombination repair (HRR) gene alteration
  • Metastatic disease as documented by conventional imaging with computed tomography (CT) or magnetic resonance imaging (MRI) (for soft tissue lesions) or 99mTc bone scan (for bone lesions). Participants with a single bone lesion on Technetium-99m (99mTc) bone scan with no other non-nodal metastatic disease must have confirmation of bone metastasis by CT or MRI. Participants with lymph node-only disease are not eligible
  • Androgen deprivation therapy (either medical or surgical castration) must have been started >=14 days prior to randomization and participants be willing to continue androgen deprivation therapy (ADT) through the treatment phase
  • Other allowed prior therapy for metastatic castration-sensitive prostate cancer (mCSPC): (a) maximum of 1 course of radiation and 1 surgical intervention for symptomatic control of prostate cancer (example, uncontrolled pain, impending spinal cord compression or obstructive symptoms). Participants with radiation or surgical interventions to all known sites of metastatic disease will be excluded from trial participation. Radiation must be completed prior to randomization (b) Up to a maximum of 6 months of ADT prior to randomization; (c) Up to a maximum of 45 days of abiraterone acetate + prednisone (AA-P) prior to randomization (d) Up to a maximum of 2 weeks of ketoconazole for prostate cancer prior to randomization

Exclusion Criteria:

  • Prior treatment with a poly (adenosine diphosphate-ribose) polymerase (inhibitor) (PARP) inhibitor
  • History of adrenal dysfunction
  • Long-term use of systemically administered corticosteroids (greater than [>] 5 milligrams [mg] of prednisone or the equivalent) during the study is not allowed. Short-term use (<=4 weeks, including taper) and locally administered steroids (for example, inhaled, topical, ophthalmic, and intra-articular) are allowed, if clinically indicated
  • History or current diagnosis of myelodysplastic syndrome (MDS)/ acute myeloid leukemia (AML)

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

Patients' Preferences in the Treatment of Hormone-sensitive Metastatic Prostate Cancer: a Discrete Choice Experiment


Condition: Prostate Cancer Metastatic, Radiotherapy Side Effect, Surgery, Urologic Cancer, Quality of Life, Patient Satisfaction, Health Care Utilization

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT04590976

Sponsor: Imperial College London

Phase:

Eligibility:

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

Inclusion Criteria:

  1. Diagnosed with prostate cancer within 4 months of screening visit
  2. Performance status 0-2

Exclusion Criteria:

  1. Castrate-resistant metastatic prostate cancer
  2. Patient has consented to a form of local cytoreductive treatment to prostate
  3. Patient has consented to a form of metastasis directed therapy

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

A Randomized, Double-blind, Placebo-controlled Phase 3 Study of Darolutamide in Addition to Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Men With Metastatic Hormone-sensitive Prostate Cancer (mHSPC)


Condition: Prostatic Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04736199

Sponsor: Bayer

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • Histologically or cytologically confirmed adenocarcinoma of prostate
  • Metastatic disease
  • Started ADT (LHRH agonist/antagonist or orchiectomy) with or without first generation anti-androgen, but no longer than 12 weeks before randomization
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1 or 2
  • Adequate bone marrow, liver and renal function

Exclusion Criteria:

  • Prior treatment with: LHRH agonist/antagonists except neoadjuvant and /or adjuvant therapy; Second-generation androgen receptor (AR) inhibitors such as enzalutamide, darolutamide, apalutamide or other investigational AR inhibitors; Cytochrome P17 enzyme inhibitor such as abiraterone acetate or oral ketoconazole as antineoplastic treatment for prostate cancer; Chemotherapy including docetaxel or immunotherapy for prostate cancer; Use of systemic corticosteroid with dose greater than the equivalent 10 mg of prednisone/day within 28 days prior to randomization
  • Treatment with radiotherapy within 2 weeks before randomization
  • Contraindication to iodinated CT and gadolinium chelate MRI intravenous contrast agent(s)
  • Had any of the following within 6 months before randomization: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, congestive heart failure (New York Heart Association Class III or IV)
  • Uncontrolled hypertension as indicated by a resting systolic BP ≥ 160 mmHg or diastolic BP ≥ 100 mmHg despite medical management
  • A gastrointestinal (GI) disorder or procedure which is expected to interfere significantly with absorption of study drug
  • Any prior malignancy (other than adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) within 5 years prior to randomization
  • Inability to swallow oral medications

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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: evaluable disease or one new bone lesion by bone scan
  8. 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 × 109/L OR absolute neutrophil count (ANC) ≥1.5 × 109/L. ii. Platelets ≥100 × 109/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. 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 of childbearing potential: Partner and/or patient must use a method of birth control with adequate barrier protection, deemed acceptable by the principal investigator during the study and for 6 months after last study drug administration.
  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:

  1. Patients are excluded from the study if any of the following criteria apply:
  2. Prostate cancer with known significant (>10%) sarcomatoid or spindle cell or neuroendocrine components. Any small cell component in the cancer should result in exclusion.
  3. 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.
  4. 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.
  5. Prior treatment with systemic radionuclides (e.g. radium-223, rhenium-186, strontium 89).
  6. Prior immuno-therapy, except for sipuleucel-T.
  7. Prior PSMA-targeted radioligand therapy, e.g., Lu-177-PSMA-617, I 131-10
  8. Prior poly ADP ribose polymerase (PARP) inhibitor for prostate cancer.
  9. Patients who have had 2 or more lines of ARATs.
  10. Patients receiving bone-targeted therapy (e.g. denosumab, zoledronic acid) must be on stable doses for at least 4 weeks prior to randomization.
  11. Administration of an investigational agent ≤60 days or 5 half-lives, whichever is shorter, prior to randomization.
  12. Major surgery ≤30 days prior to randomization.
  13. Estimated life expectancy <6 months as assessed by the principal investigator.
  14. Presence of liver metastases >1 cm on abdominal imaging.
  15. 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
  16. Use of opioids for cancer-related pain ≤30 days prior to consent.
  17. Known presence of central nervous system metastases.
  18. Contraindications to the use of planned ARAT therapy.
  19. Active malignancy other than low-grade non-muscle-invasive bladder cancer and non melanoma skin cancer.
  20. Concurrent illness that may jeopardize the patient's ability to undergo study procedures.
  21. 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.
  22. Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
  23. 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.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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 and non-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 non-measurable disease must have documented rising PSA levels or appearance of new lesion according to PCWG3
  • Participants with known breast cancer gene (BRCA) mutations are excluded
  • No prior radioscope therapy or radiotherapy to ≥30% of bone marrow
  • Cohort 8: Melanoma
  • Must have histologically or cytotoxically confirmed cutaneous malignant melanoma
  • Participants with mucosal, acral, or uveal melanoma are excluded
  • Must have locally advanced unresectable or metastatic stage disease
  • Must have measurable disease
  • Must have progressive disease following anti-PD(L)1 therapy

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
  • Active viral, bacterial, or fungal infection requiring systemic treatment within 7 days prior to the first dose of LV
  • Any ongoing clinically significant toxicity associated with prior treatment (Grade 2 or higher)
  • Ongoing sensory or motor neuropathy of Grade ≥2
  • Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with congestive heart failure
  • Has received prior radiotherapy within 2 weeks of start of study treatment
  • Has received a live vaccine within 30 days of the planned start of study therapy.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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).

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

A Phase 1/2a Open-label, Multicenter, Dose Escalation and Dose Expansion Study of the Safety, Tolerability, and Pharmacokinetics of HPN424 in Patients With Advanced Prostate Cancer Refractory to Androgen Therapy


Condition: Advanced Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03577028

Sponsor: Harpoon Therapeutics

Phase: Phase 1/Phase 2

Eligibility:

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

Key Inclusion Criteria:

  1. Male patients ≥18 years of age
  2. Histologically or cytologically confirmed adenocarcinoma of the prostate
  3. Progressive metastatic castrate-resistant prostate cancer (mCRPC):
  4. Serum testosterone levels less than 50 ng/dL (or ≤0.50 ng/mL or 1.73 nmol/L) within 28 days prior to start of study drug
  5. Radiographic evidence of metastatic disease
  6. Disease progression on the prior systemic regimen
  7. Must have received at least 2 prior systemic therapies approved for mCRPC
  8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  9. Adequate bone marrow function
  10. Able to read, understand and provide written informed consent

Key Exclusion Criteria:

  1. Previously treated or current brain metastases
  2. Untreated spinal cord compression. Participants must be neurologically stable off steroids for at least 4 weeks prior to first dose of study drug
  3. Concurrent treatment with anti-tumor necrosis factor (TNF) alpha therapies, systemic corticosteroids (prednisone dose >10 mg per day or equivalent), or other immune suppressive drugs within the 2 weeks prior to first dose of study drug
  4. History of or known or suspected autoimmune disease (exception(s): patients with vitiligo, resolved childhood atopic dermatitis, hypothyroidism, or hyperthyroidism that is clinically euthyroid at Screening are allowed)
  5. History of clinically significant cardiovascular disease such as symptomatic congestive heart failure (CHF), myocardial infarction within 6 months before first dose of study drug, history of thromboembolic event within 3 months before first dose of study drug
  6. Known active or chronic hepatitis B or hepatitis C as demonstrated by hepatitis B surface antigen (HBsAg) positivity and/or anti-hepatitis C virus (HCV) positivity, respectively, or known history of human immunodeficiency virus (HIV) seropositive status
  7. Clinically active liver disease, including liver cirrhosis that is Child-Pugh class B or C
  8. Second primary malignancy that has not been in remission for at least 3 years.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
email news signup