Prostate Cancer

Condition: Metastatic Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06582628

Sponsor: Fundacion Oncosur

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

1. Male age 18 or older.
2. Histological diagnosis of prostate adenocarcinoma without neuroendocrine differentiation or small cell features.
3. Willing and able to provide written informed consent to participate in the study. Written consent must be given before registration, according to International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) / Good clinical practice (GCP), and national/local regulations.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
5. Willing to provide tumor biopsies during the study. Note: At study entry, the pre-treatment fresh tumor biopsy could be replaced by an archived tumor biopsy upon agreement from the study chief investigator if such biopsy has been taken after progression to metastatic castration resistance and has both archived fresh-frozen material and a Formalin-fixed and paraffin-embedded (FFPE) block with a minimum tumor content more less than30 percent. Still the patient must be amenable and willing to undergo a new mandatory post-treatment biopsy.
6. Willing to provide blood samples for biomarker analysis.
7. Willing to give consent to sequencing of DNA damage repair (DDR) genes for analysis of the prevalence of somatic and germline aberrations in DNA damage repair genes.
8. Metastatic (M1) prostate cancer documented by bone scan, or soft tissue disease documented by computed tomography (CT), or magnetic resonance imaging (MRI).
9. Asymptomatic or minimally symptomatic prostate cancer at screening.
10. Estimated life expectancy of greater than or equal to 6 months from screening.
11. Ongoing androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone (GnRH) agonist or antagonist for participants who have not undergone bilateral orchiectomy must be in place before screening and must continue throughout the study. 12 .Disease progression after at least 12 weeks of treatment with abiraterone for metastatic hormone-sensitive prostate cancer. Progression is defined as: a. PSA rise of greater than or equal to 25 percent and an absolute increase of greater than or equal to 2 ng/mL above nadir (or baseline for participants with no PSA decline), confirmed by a second PSA value at least 3 weeks later. and / or b. Limited radiographic progression: maximum of 2 new bone metastases, no new soft tissue metastasis and less than50percentincrease in the size of measurable soft tissue lesions.
12. Participants who have received prior docetaxel must meet the following criteria: a. Received a maximum of 6 cycles of docetaxel for mHSPC. b. Received the last dose of docetaxel higher than 6 months prior to randomization.
13. Adequate organ function within 28 days before the first study treatment on Day 1, defined by the following:
14. Haemoglobin greater than or equal to 10 g/dL, no blood transfusions within 14 days before obtaining the haematology laboratory tests at screening,
15. Platelets greater than or equal to 100,000/μL no platelets transfusions within 14 days before obtaining the haematology laboratory tests at screening,
16. Neutrophils greater than or equal to 1500/μL, no growth factors given within 14 days before obtaining the haematology laboratory tests at screening,
17. Serum creatinine less than1.5X ULN or calculated creatinine clearance greater than or equal to 50 mL/min
18. Albumin greater than 3 g/dL,
19. AST or ALT less than 2.5 × ULN (less than 5 × ULN if liver function abnormalities are due to hepatic metastasis).
20. Total serum bilirubin less than 1.5 × ULN (less than 3 × ULN for participants with documented Gilbert syndrome or for whom indirect bilirubin concentrations suggest an extrahepatic source of elevation).
21. Ability to swallow study medication tablets and comply with study requirements.
22. Agrees to use a condom 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, starting contraception at screening and continue throughout the study period and for 3 months after the final treatment administration, unless the patient is unable to maintain intercourse due to the androgen deprivation.
23. Subjects must not donate sperm starting at screening and throughout the study period and for 3 months after the final abiraterone acetate administration.
24. Subject agrees not to participate in another interventional study while on treatment.
25. Willing and able to comply with all scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion Criteria:

1. Prior abiraterone treatment for less than 12 weeks or disease progression (either PSA or radiographic progression) within 6 months of starting abiraterone.
2. Disease progression less than 6 months after the last administration of docetaxel for mHSPC.
3. Known or suspected brain metastasis or active leptomeningeal disease.
4. A finding of superscan in a bone scan at screening. Superscan is defined as a bone scan which demonstrates markedly increased skeletal radioisotope uptake relative to soft tissues in association with absent or faint renal activity (absent kidney sign).
5. Symptomatic or impending spinal cord compression or cauda equina syndrome.
6. Use of opiate analgesia for pain from prostate cancer with average Brief pain inventory (BPI) questionnaire score higher than 6 and/or uncontrolled prostate cancer-related pain requiring increasing doses of opiates within 4 weeks prior to randomization
7. Prior treatment with an AR-targeted therapy (enzalutamide, apalutamide, darolutamide, ketoconazole) other than abiraterone for mHSPC; chemotherapy other than 6 cycles of docetaxel for mHSPC, immunotherapy or radiopharmaceuticals.
8. Therapeutic radiation therapy within, 14 days (7 days for limited-field palliative radiotherapy) prior to study enrolment, or participants who have not recovered from radiotherapy-related toxicities to grade less than or equal to 1 according to NCI-CTCAE v.5.
9. Major surgery within 4 weeks prior to randomization or participants who have not recovered from the side effects of any major surgery.
10. Administration of an investigational therapeutic or invasive surgical procedure (not including surgical castration) within 30 days of Cycle 1 Day 1 or currently enrolled in an investigational study.
11. History of seizure or any condition that may predispose to seizure (i.e., prior significant brain trauma, brain vascular malformation, etc) or subjects that have had an unexplained loss of consciousness or transient ischemic attacks within 1 year previous to scheduled day 1 of treatment.
12. Congenital long QT syndrome or ECG at screening with QT interval corrected using Fridericia's formula (QTcF) greater than 500 milliseconds.
13. articipants with clinically significant cardiovascular disease including but not limited to any of the following:
14. Stroke, transient ischemic attack, unstable angina pectoris or documented myocardial infarction within 12 months prior to study entry.
15. Symptomatic pericarditis or clinically significant pericardial effusion or myocarditis
16. Documented congestive heart failure (New York Heart Association Class, NYHA functional classification III-IV)
17. Uncontrolled, persistent hypertension defined as systolic blood pressure less than 170mmHg or diastolic blood pressure less than100mmHg. Subjects with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
18. Participants with any of the following cardiac conduction abnormalities: Ventricular arrhythmias except for benign premature ventricular contractions
19. Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication.
20. Conduction abnormality requiring a pacemaker.
21. Other cardiac arrhythmia not controlled with medication.
22. Any clinically significant gastrointestinal disorder affecting absorption (i.e., extensive small bowel resection, active inflammatory bowel disease).
23. Active or symptomatic viral hepatitis or chronic liver disease.
24. Known/possible hypersensitivity, allergies to enzalutamide, talazoparib or any of capsule excipients.
25. Other malignancy except:
26. Carcinoma in situ or non-melanoma skin cancer.
27. A cancer diagnosed and treated greater than or equal to 5 years before randomization with no subsequent evidence of recurrence.
28. Any condition or situation which, in the opinion of the investigator, would put the subject at risk, may confound study results, or interfere with the subject's participation in this study.

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Condition: Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Castration-Resistant Prostate Carcinoma, Clinical Stage III Gastric Cancer AJCC v8, Clinical Stage IV Gastric Cancer AJCC v8, HER2-Positive Breast Carcinoma, Locally Advanced Breast Carcinoma, Locally Advanced Gastric Carcinoma, Locally Advanced Malignant Solid Neoplasm, Locally Advanced Ovarian Carcinoma, Locally Advanced Pancreatic Carcinoma, Locally Advanced Prostate Carcinoma, Metastatic Breast Carcinoma, Metastatic Gastric Carcinoma, Metastatic Malignant Solid Neoplasm, Metastatic Ovarian Carcinoma, Metastatic Pancreatic Carcinoma, Metastatic Prostate Carcinoma, Platinum-Sensitive Ovarian Carcinoma, Recurrent Breast Carcinoma, Recurrent Gastric Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Pancreatic Carcinoma, Recurrent Prostate Carcinoma, Stage II Pancreatic Cancer AJCC v8, Stage III Ovarian Cancer AJCC v8, Stage III Pancreatic Cancer AJCC v8, Stage III Prostate Cancer AJCC v8, Stage IV Ovarian Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8, Stage IV Prostate Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04550494

Sponsor: National Cancer Institute (NCI)

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

• Adult patients with solid tumors and documented germline or somatic aberrations in genes involved in DNA damage response (DDR) and whose disease has progressed following at least one standard therapy or who have no acceptable standard treatment options. Molecular testing performed at an National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) (NCT02465060) study-designated Clinical Laboratory Improvement Act (CLIA) laboratory or at Myriad Genetics, GeneDx, Invitae, or the Frederick National Laboratory for Cancer Research (FNLCR) Molecular Characterization Laboratory (MoCha) will be acceptable for determination of eligibility
• Patients with the following germline or somatic genetic aberrations will be eligible based on compelling preclinical and/or clinical data suggesting that these deleterious mutations confer sensitivity to PARP inhibitors; no more than 6 patients (across both cohorts) with an eligibility mutation in any one gene will be enrolled
• Deleterious BRCA1 or BRCA2 mutations
• Loss of function mutations (including novel loss of function frameshift or nonsense mutations) in the following Fanconi anemia genes: FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, FANCN
• A known functional mutation (including novel loss of function frameshift or nonsense mutations) in any of the following DDR genes: ARID1A, ATM, ATR, BACH1 (BRIP1), BAP1, BARD1, CDK12, CHK1, CHK2, IDH1, IDH2, MRE11A, NBN, PALB2, RAD50, RAD51, RAD51B, RAD51C, RAD51D, RAD54L
• Age >= 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Life expectancy of greater than 3 months
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 10 g/dL
• Total bilirubin =< 1.5 x institutional upper limit of normal (=< 3 x upper limit of normal in the presence of documented Gilbert's syndrome or liver metastases at baseline)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x institutional upper limit of normal
• Creatinine =< 1.5 x institutional upper limit of normal OR Creatinine clearance (CrCl) >= 60 mL/min/1.73m^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73m^2
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) by chest x-ray or as >= 10 mm (>= 1 cm) with CT scan, MRI, or calipers by clinical exam
• Patients must have a tumor site amenable to biopsy. If avoidable, the lesion for biopsy should not be selected as a target lesion for RECIST measurements
• The effects of talazoparib on the developing human fetus are unknown. For this reason and because PARP inhibitors are known to be teratogenic, women of child-bearing potential must agree to use a highly effective method of contraception for the duration of study participation and for at least 7 months after completing study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Male patients with female partners of reproductive potential and pregnant partners who are treated or enrolled on this protocol must also agree to use adequate contraception for the duration of study participation and for at least 4 months after completion of talazoparib administration
• Patients must be able to swallow whole tablets or capsules. Nasogastric or gastric-tube (G-tube) administration is not allowed. Any gastrointestinal disease which would impair ability to swallow, retain, or absorb drug is not allowed
• Ability to understand and the willingness to sign a written informed consent document
• Patients must have recurrent, locally advanced or metastatic disease
• Patients must have progressed on or after at least one line of standard-of-care (SOC) intervention, except for those patients without SOC or for whom talazoparib is SOC
• PATIENTS WITH OVARIAN CANCER:
• All patients with ovarian cancer should have one prior platinum-based therapy
• Patients with ovarian cancer with platinum-sensitive disease are eligible. Patients with platinum-refractory disease are not eligible
• Patients with gBRCAm ovarian cancer must also have progressed on a PARP inhibitor. The time and treatment between the prior PARP inhibitor and protocol initiation must be documented
• PATIENTS WITH PANCREATIC CANCER:
• All patients with pancreatic cancer should have received prior platinum-containing therapy in the metastatic setting
• PATIENTS WITH BREAST CANCER:
• Patients with HER2+ breast cancer should have had 2 prior systemic lines of therapy in the metastatic setting, including anti-HER2 therapy
• Patients with breast cancer who are eligible for a PARP inhibitor by Food and Drug Association (FDA) approvals must have had prior PARP inhibitor as per FDA indication. The time and treatment between the prior PARP inhibitor and protocol initiation must be documented
• PATIENTS WITH GASTRIC CANCER:
• Patients with HER2+ gastric cancer should have had received anti-HER2 therapy in the metastatic setting
• PATIENTS WITH PROSTATE CANCER:
• Patients with prostate cancer who are eligible for a PARP inhibitor by FDA approvals must have had prior PARP inhibitor for eligibility. The time and treatment between the prior PARP inhibitor and protocol initiation must be documented
• All patients with prostate cancer can continue to receive treatment with gonadotropin-releasing hormone (GnRH) agonists while on study, as long as there is evidence of disease progression on prior therapy
• Patients with castration resistant prostate cancer must have castrate levels of testosterone (< 50 ng/dL [1.74 nmol/L])
• Patients with metastatic hormone receptor (HR) prostate cancer and mutations in either BRCA1, BRCA2, or ATM should continue to receive anti-androgen receptor (anti-AR) therapy

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 4 weeks or 5 half-lives, whichever is shorter (6 weeks for nitrosoureas or mitomycin C). Patients must be >= 2 weeks since any prior administration of a study drug in a phase 0 or equivalent study and be >= 1 week from palliative radiation therapy. Patients must have recovered to eligibility levels from prior toxicity or adverse events
• Patients who have had prior treatment with talazoparib are ineligible
• Patients who have had prior monoclonal antibody therapy must have completed that therapy >= 6 weeks (or 3 half-lives of the antibody, whichever is shorter) prior to enrollment on protocol (minimum of 1 week between prior therapy and study enrollment) except for monoclonal antibody therapies that have been proven to be safe when combined with PARP inhibitor (PARPi) treatment (such as anti-PD-1/PD-L1 and anti-HER2), which must be completed >= 4 weeks prior to enrollment
• Patients who are receiving any other investigational agents
• Patients with active brain metastases or carcinomatous meningitis are excluded from this clinical trial. Patients with treated brain metastases, whose brain metastatic disease has remained stable for >= 1 month without requiring steroid and anti-seizure medication are eligible to participate
• Eligibility of subjects receiving any medications or substances with the potential to affect the activity or pharmacokinetics of talazoparib will be determined following review by the principal investigator
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because the effects of the study drugs on the developing fetus are unknown
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• Patients who require use of coumarin-derivative anticoagulants such as warfarin are excluded. Low-dose warfarin (=< 1 mg/day) is permitted
• Women who are currently lactating
• History of prior malignancies within the past 3 years other than non-melanomatous skin cancers that have been controlled

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Condition: Castration-Sensitive Prostate Carcinoma, Metastatic Prostate Adenocarcinoma, Stage IV Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04734730

Sponsor: City of Hope Medical Center

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

• All patients must have a histologically or cytologically proven diagnosis of adenocarcinoma of the prostate. (Note: Gleason score not required if biopsy of metastasis was used to make the histologic diagnosis)
• All patients must have metastatic disease: either soft tissue and/or bony metastases prior to initiation of androgen. Measurable disease is not required
• Baseline imaging must have been performed within 42 days before or 14 days after initiating luteinizing hormone releasing hormones (LHRH) therapy. All disease must be assessed and documented on the Baseline Tumor Assessment Form
• Patients may have started on LHRH therapy for metastatic prostate cancer provided this was initiated no longer than 60 days prior to registration
• Patients may have received neoadjuvant and/or adjuvant LHRH therapy during definitive treatment or salvage radiation; if so at least 12 months must have elapsed from the last LHRH injection and baseline testosterone must be > 150 ng/dL
• No restriction on bicalutamide used for flare prevention or combined therapy however bicalutamide must be stopped at registration
• Patients must have a Karnofsky performance status of 60
• 100
• Men of reproductive potential and those who are surgically sterilized (i.e., vasectomy) must agree to practice effective barrier contraception or agree to abstain from intercourse while receiving treatment on this study and for at least 4 months after protocol treatment ends
• Bilirubin =< 2 x institutional upper limit of normal (ULN) (obtained within 28 days prior to registration)
• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x institutional ULN, or =< 5 x institutional ULN if liver metastases are present (obtained within 28 days prior to registration)
• Calculated creatinine clearance >= 30 mL/min using a serum creatinine obtained within 28 days prior to registration
• Leukocytes >= 3,000/mcL (obtained within 28 days prior to registration)
• Absolute neutrophil count (ANC) >= 1,500/mcL (obtained within 28 days prior to registration)
• Hemoglobin >= 9 g/dL (obtained within 28 days prior to registration)
• Platelets >= 100,000/mcL (obtained within 28 days prior to registration)
• All subjects must have the ability to understand and the willingness to sign a written informed consent
• Patients may have received prior androgen deprivation therapy (ADT) -neoadjuvant and/or adjuvant, or in conjunction with salvage radiation
• but it must not have lasted for more than 36 months. Single or combination therapy allowed. At least 6 months must have elapsed since completion of androgen deprivation therapy in the neoadjuvant and/or adjuvant setting, and serum testosterone must be > 150 ng/mL within 28 days prior to registration. Note: Serum testosterone assessment is required for eligibility for only those with prior treatment with ADT
• Patients who have already started on LHRH therapy are eligible, provided no more than 60 days have elapsed from LHRH injection (or surgical castration) for metastatic prostate cancer prior to registration. The start date of medical castration is considered the day the patient first received an injection of a LHRH agonist/antagonist (or orchiectomy), not an oral antiandrogen. Subjects may not already be taking abiraterone, enzalutamide, apalutamide or other intensification agent during this time
• bicalutamide is permitted
• Patients may have received palliative radiotherapy for symptomatic bone or visceral metastasis, provided they have recovered from all side effects at the time of registration
• Patients may have received prior surgery. For all major surgeries, at least 14days must have elapsed since completion and patient must have recovered from all major side effects of surgery per investigator's assessment
• Patients may have received or plan to receive concurrent bone targeting agents that do not have an effect on prostate specific antigen (PSA) (e.g. denosumab or bisphosphonate)

Exclusion Criteria:

• Patients must not have received prior and/or must not have any plans for receiving concomitant therapy with ketoconazole, aminoglutethimide, or enzalutamide (MDV3100). Concurrent megestrol for hot flashes is allowed
• Patients must not have received any prior cytotoxic chemotherapy for metastatic prostate cancer
• Prior cytotoxic chemotherapy with curative intent in the neoadjuvant or adjuvant setting may be allowed at the discretion of the principal investigator. At least 2 years must have elapsed since completion of cytotoxic chemotherapy in the neoadjuvant and/or adjuvant setting
• Patients with known brain metastases are not eligible. Brain imaging studies are not required for eligibility if the patient has no neurologic signs or symptoms suggestive of brain metastasis. But, if brain imaging studies are performed, they must be negative for disease
• Patients must not have New York Heart Association class III or IV heart failure at the time of screening. Patients must not have any thromboembolic event, unstable angina pectoris, myocardial infarction, or serious uncontrolled cardiac arrhythmia within 6 months prior to registration
• Patients must not have uncontrolled hypertension (defined as blood pressure > 160 mmHg systolic and > 90 mmHg diastolic at 2 separate measurements no more than 60 minutes apart) despite appropriate medical therapy. Note: Patients may be rescreened after adjustments of antihypertensive medications
• Patients must not be known to have human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C, life-threatening illness unrelated to cancer, or any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with participation in this study
• Patients with a known history of primary and secondary adrenal insufficiency are not eligible
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to any of the study drugs
• Patients may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy. Previous experimental therapy must have been completed at least 28 days prior to registration
• Patients must not have known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption or tolerance of any of the study drugs, including difficulty swallowing oral medications
• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years

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Condition: Advanced Solid Tumor, Diffuse Large B Cell Lymphoma, Lymphoma, T-Cell, Mesothelioma, Malignant, Prostatic Neoplasms, Castration-Resistant, Endometrial Cancer, Ovarian Clear Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04104776

Sponsor: Constellation Pharmaceuticals

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

• Phase 1 Eligible Phase 1 patients are adults who have a confirmed locally advanced or metastatic tumors (solid tumors or lymphoma) that have relapsed following standard therapy or progressed through standard therapy or who have a disease for which no standard effective therapy exists. Phase 2:
• Life expectancy of ≥ 12 weeks
• ECOG 0-1
• Adequate bone marrow function
• Adequate renal function
• Adequate liver function For Cohort M1, the following criteria should be considered:
• Histologically confirmed locally advanced unresectable or metastatic urothelial carcinoma with predominant urothelial histology
• • Histologically confirmed metastatic solid tumor (except ovarian clear cell cancer, endometrial cancer, and pleural or peritoneal mesothelioma)
• Known ARID1A mutation (NGS testing)
• Disease progression during or following prior chemotherapy approved therapies or for which no standard therapy exists
• Measurable disease per RECIST 1.1 For Cohort M2, the following criteria should be considered:
• Histologically confirmed advanced ovarian clear cell carcinoma
• Known ARID1A mutation (by NGS testing)
• Received at least 1 line of platinum-based chemotherapy and must have received bevacizumab as part of any line of treatments unless contraindicated or locally not approved or locally not accessible
• Measurable disease per RECIST 1.1
• Patient must have disease progression after previously receiving effective and available standard of care treatment for clear cell ovarian cancer per local clinical practice For Cohort M3, the following criteria should be considered:
• Histologically or cytologically confirmed recurrent, metastatic, or unresectable endometrial carcinoma
• Known ARID1A mutation (by NGS testing)
• Received at least 1 line of platinum-based regimen in recurrent/metastatic setting
• Documented microsatellite instability (MSI)-high or deficient mismatch repair (dMMR) or patients who have non-dMMR/microsatellite stable tumors should have received an anti-PD-1 or anti-PD-L1 agent alone or in combination with the approved agents as applicable, as part of their prior treatments unless considered not eligible, contraindicated or if not locally approved
• Brachytherapy is allowed if completed >12 weeks before the first dose of study drug
• Measurable disease per RECIST 1.1
• Patients must have previously received effective and available standard of care treatment options for endometrial cancer per local clinical practice unless these are contraindicated For Cohort M4, the following criteria should be considered:
• PTCL or DLBCL with the following criteria:
• PTCL
• Documented refractory, relapsed, or progressive disease after at least 1 prior line of systemic therapy. Refractory is defined as:
• Failure to achieve CR after first-line therapy
• Failure to reach at least PR after second-line therapy or beyond
• Must have at least 1 prior line of systemic therapy for PTCL.
• Participants must be considered hematopoietic cell transplantation (HCT) ineligible during screening due to disease status (active disease), comorbidities, or other factors; the reason for HCT ineligibility must be clearly documented.
• In the PTCL cohort, participants with anaplastic large cell lymphoma (ALCL) must have prior brentuximab vedotin treatment.
• DLBCL:
• Relapsed or refractory disease following 2 or more prior lines of standard therapy.
• Not considered candidates to receive CAR-T or autologous hematopoietic stem cell transplant (ASCT) as assessed by the treating investigator for reasons such as age, underlying comorbidities, performance status, or due to disease progression after previously received ASCT or CAR-T. The reason for transplant ineligibility must be clearly documented.
• For patients who underwent past ASCT or CAR-T treatment, at least 90 days must have elapsed since the start of the procedure. For all other patients, at least 8 weeks must have elapsed since their most recent systemic anti-DLBCL therapy For Cohort M5, the following criteria should be considered:
• Pleural or peritoneal relapsed/refractory mesothelioma
• Must have progressed on or after at least 1 prior line of active therapy
• Measurable disease per modified RECIST 1.1 for pleural mesothelioma or by RECIST 1.1 for peritoneal mesothelioma
• Known BAP1 loss per immunohistochemistry (IHC) or NGS For Cohort M6, the following criteria should be considered:
• Have measurable soft-tissue disease
• Documented metastatic disease
• Disease progression while on prior therapies
• Baseline testosterone ≤50 ng/dL (≤2.0 nM) and surgical or ongoing medical castration must be maintained throughout the duration of the study

Exclusion Criteria:

• Medical Conditions
• Previous solid organ or allogeneic hematopoietic cell transplant (HCT)
• Known symptomatic untreated brain metastases
• Clinically significant cardiovascular disease
• Major surgery within 4 weeks before starting study drug or not recovered from any effects of prior major surgery
• Gastrointestinal disorders or any other condition that may significantly interfere with absorption of the study medication by Investigator's assessment.
• Uncontrolled active infection requiring intravenous antibiotic, antiviral, or antifungal medications within 14 days before the first dose of study drug. Infections (eg, urinary tract infection) controlled on concurrent antimicrobial agents and antimicrobial prophylaxis per institutional guidelines are acceptable.
• Suspected pneumonitis or interstitial lung disease or a history of pneumonitis or interstitial lung disease.
• Have a history of a concurrent or second malignancy. Patients with a history of T-cell lymphoblastic lymphoma or T-Cell lymphoblastic leukemia are not eligible.
• Have current known active or chronic infection with HIV, hepatitis B, or hepatitis C. Screening of patients with serologic testing for these viruses is not required
• Clinically active or symptomatic viral hepatitis or chronic liver disease.
• Unstable or severe uncontrolled medical condition or any important medical or psychiatric illness or abnormal laboratory finding
• Previous solid organ or allogeneic hematopoietic cell transplant HCT. Prior/Concomitant Therapy:
• Prior anticancer treatment:
• Prior systemic anticancer treatment with chemotherapy, targeted therapy, small molecule, antibody, or investigational anticancer therapy (includes prior PD-1 or PD-L1 therapy), or other anticancer therapeutic with the exception of gonadotropin releasing hormone analogues, within 4 weeks (or 5 half-lives), whichever is shorter, before the first dose of study drug (6 weeks washout for nitrosoureas or mitomycin C).
• Previous treatment with an EZH2 inhibitor
• Prior radiation therapy within 4 weeks before first dose of study drug
• Prior stereotactic body radiation therapy within 2 weeks before first dose of study drug
• Prior chemoembolization or radioembolization within 4 weeks before first dose of study drug.
• Concomitant medication(s) or food or beverage that are strong CYP3A inducers or inhibitors within 7 days prior to the first dose of study drug. Other Exclusions • Breastfeeding or pregnant woman or expecting to conceive or father children within the projected duration of the trial, starting with the Screening visit through 183 days after the last dose of study drug. Cohort M6 (mCRPC) only
• Bone-only disease without nodal disease and no evidence of visceral spread
• Structurally unstable bone lesions concerning for impending fracture
• Herbal products that may decrease prostate-specific antigen within 4 weeks prior to Day 1 of treatment and while on study
• Treatment for prostate cancer (First generation androgen receptor antagonists within 4 weeks; 5α-reductase inhibitors, ketoconazole, estrogens, or progesterones within 2 weeks)
• Planned palliative procedures such as radiation therapy or surgery

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Condition: Metastatic Castration-Resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06629779

Sponsor: Pfizer

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

• Male participants aged ≥18 years (or the minimum age of consent in accordance with local regulations) at screening.
• Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features.
• Metastatic disease in bone documented on bone scan, or in soft tissue documented on CT/MRI scan.
• Surgically or medically castrated, with serum testosterone ≤50 ng/dL (≤1.73 nmol/L) at screening.
• Metastatic disease in bone documented on bone scan, or in soft tissue documented on CT/MRI scan.
• Progressive disease in the setting of medical or surgical castration.
• Prior to randomization, there must be resolution of acute effects of any prior therapy to either baseline severity or CTCAE Grade ≤1.
• ECOG performance status 0 or 1, with a life expectancy of ≥12 months as assessed by the investigator.

Exclusion Criteria:

• Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Clinically significant cardiovascular disease.
• Known or suspected brain metastasis or active leptomeningeal disease.
• Participants must be treatment naïve at the mCRPC stage, eg, participants cannot have received any cytotoxic chemotherapy with the following exceptions: Treatment with first-generation antiandrogen (ADT) agents and. Docetaxel treatment is allowed for mCSPC.
• Previous administration with an investigational product (drug or vaccine) within 30 days.
• Current use or anticipated need for drugs that are known strong CYP3A4/5 inhibitors and inducers (with exception of enzalutamide as part of this study).
• Major surgery or palliative localized radiation therapy within 14 days before randomization.
• Inadequate organ function.

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Condition: Metastatic Castrate Resistant Prostate Cancer (mCRPC)

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06551324

Sponsor: Pfizer

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features.
• Metastatic disease in bone documented on bone scan, or in soft tissue documented on CT/MRI scan.
• Progressive disease in the setting of surgical or medical castration with evidence of disease progression on treatment with abiraterone acetate in the mCSPC setting or first line mCRPC setting is required.
• Eastern Cooperate Oncology Group (ECOG) performance status 0
• 2, with life expectancy of at least 6 months as assessed by the investigator.

Exclusion Criteria:

• Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may make the participant inappropriate for the study.
• Know history of active inflammatory gastrointestinal disease, chronic diarrhea, or previous gastric resection or lap-band surgery.
• Clinically significant cardiovascular disease.
• Known or suspected brain metastasis or active leptomeningeal disease or clinically significant history of seizure.
• Prior treatment for prostate cancer at any stage with any cytotoxic chemotherapy, radioligand therapy (i.e. 177Lu-PSMA-617, radium 223), androgen receptor signaling inhibitors (ARSi) including enzalutamide, apalutamide, darolutamide, poly ADP-ribose polymerase (PARP) monotherapy or other systemic anti-cancer treatment, with the following exceptions: 1. Treatment with first-generation antiandrogen agents, if discontinued prior to first dose of study intervention. 2. Docetaxel treatment is allowed for mCSPC, as long as no signs of failure, or disease progression occurred during treatment or within 3 months of treatment completion.
• Previous administration with an investigational product within 30 days or 5 half-lives preceding the first dose of study intervention (whichever is shorter).
• Inadequate organ function.

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Condition: Hormone-refractory Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05997615

Sponsor: Amunix, a Sanofi Company

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

• Has histological, pathological, and/or cytological confirmation of prostate adenocarcinoma OR metastatic disease typical of prostate cancer (ie, involving bone or pelvic lymph nodes or para-aortic lymph nodes)
• Has metastatic disease, defined by ≥1 metastatic lesion that is present on baseline CT, MRI, or bone scan imaging
• Has documented progressive mCRPC
• Have been treated with ≥ 1 prior taxane regimens (eg, docetaxel, cabazitaxel)
• Participants deemed unsuitable for standard of care
• Has Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
• Has a life expectancy more than 6 months

Exclusion Criteria:

• Presence of dominant histopathological features representative of sarcomatoid, spindle cell, or neuroendocrine small cell components
• Has acute or chronic infections
• Has a concomitant medical or inflammatory condition that may increase the risk of toxicity to AMX 500, per the Investigator
• Has lesions in proximity of vital organs
• Has known active CNS metastases and/or carcinomatous meningitis The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

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Condition: Metastatic Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05011383

Sponsor: VA Office of Research and Development

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

• Signed informed consent form (ICF) providing agreement to adhere to the dosing schedule, report for all trial visits and authorization, use and release of health and research trial information
• Male age > 18 years
• Histologically or cytologically confirmed adenocarcinoma of the prostate
• Ongoing gonadal androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) analogues, antagonists or orchiectomy. Patients who have not had an orchiectomy must be maintained on effective GnRH analogue/antagonist therapy
• Castration resistant prostate cancer as defined by serum testosterone < 50 ng/ml and one of the following:
• PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart.
• Evaluable disease progression by modified RECIST 1.1 (Response Evaluation Criteria in Solid Tumors)
• Progression of metastatic bone disease on bone scan with > 2 new lesions
• Presence of metastatic disease on bone or CT scan
• Patients must have progressed on 1 next-generation AR-signaling inhibitor (e.g. abiraterone, enzalutamide, apalutamide, darolutamide, etc.).
• Asymptomatic or minimal cancer related symptoms
• Eastern Cooperative Oncology Group (ECOG) Performance Status of < 2
• Presence of inactivating mutations in ATM, CDK12 or CHEK2 as determined by a CLIA level assay for DNA sequencing.

Exclusion Criteria:

• Currently receiving active therapy for other neoplastic disorders will not be eligible.
• Histologic evidence of small cell carcinoma (morphology alone
• immunohistochemical evidence of neuroendrocrine differentiation without morphologic evidence is not exclusionary)
• Known parenchymal brain metastasis
• Liver metastases
• Active or symptomatic viral hepatitis or chronic liver disease AST or ALT > 2.5 x ULN or total bilirubin > ULN (unless Gilbert's syndrome is the etiology of hyperbilirubinemia).
• Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of <35 % at baseline
• Patients with pain attributable to their prostate cancer and requiring the use of opioids.
• Tumor causing urinary outlet obstruction that requires catheterization for voiding. Patients that require catheterization to void secondary to benign strictures or other non-cancer causes will be permitted to enroll.
• Presence of dementia, psychiatric illness, and/or social situations limiting compliance with study requirements or understanding and/or giving of informed consent.
• Any condition(s), medical or otherwise, which, in the opinion of the investigators, would jeopardize either the patient or the integrity of the data obtained.

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

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04704505

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

• Histologically documented adenocarcinoma of the prostate confirmed by pathology report from prostate biopsy or a radical prostatectomy specimen. If prostatic tumor is of mixed histology, > 50% of the tumor must be adenocarcinoma.
• Bone metastases as manifested by one or more lesions on a Technetium 99m bone scan performed within 2 months of screening
• Castrate-resistant prostate cancer, in the setting of castrate levels of testosterone (≤ 50 ng/dL), defined as current or historical evidence of disease progression concomitant with surgical castration or androgen deprivation therapy (ADT), as demonstrated by two consecutive rises in PSA OR new lesions on bone scan:
• PSA progression will be defined as 2 rising PSA values compared to a reference value, measured at least 7 days apart and the second value is ≥ 2 ng/mL. Appearance of one or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the precastration studies if there was no response. Increased uptake of pre-existing lesions on bone scan does not constitute progression. It must be documented within 8 weeks of screening Documented bone lesions by the appearance of ≥ 2 new lesions by bone scintigraphy or dimensionally measurable soft tissue metastatic lesion assessed by CT or MRI.
• Serum PSA ≥ 2.0 ng/mL
• Patients must be on bone health agents, either zoledronic acid or denosumab, for at least 4 weeks before enrollment. These treatments must then be continued during the study.
• Screening Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Asymptomatic or minimally symptomatic disease (no opioids)
• Prior treatment with no more than one novel AR targeted drug (abiraterone, enzalutamide, darolutamide or apalutamide) is permitted, but not required. Prior first-generation AR targeted therapies such as bicalutamide or nilutamide are permitted as previous therapy and does not count as novel AR targeted therapy.
• Prior chemotherapy for hormone-sensitive prostate cancer (given ≥ 12 months prior to study entry) is allowed, but not necessary.
• Adequate bone marrow, renal and liver function (Absolute Neutrophil count > 1,000, Platelets >100,000, Hemoglobin ≥ 9g/dL aspartate aminotransferase/ alanine amino transferase (AST)/(ALT) within normal limits (WNL); Total Bilirubin WNL.
• No evidence (within 5 years) of prior malignancies (except successfully treated basal cell or squamous cell carcinoma of the skin).
• All patients must have tissue for genomic analysis. A biopsy of a metastatic site may be done during the screening; however, archive tissue will be allowed. Prostate tissue from prostate biopsy will be allowed.

Exclusion Criteria:

• The presence of known visceral metastasis, including lung, liver and brain metastases.
• Spinal cord compression, imminent long bone fracture, or any other condition that, in the opinion of the investigator, is likely to require radiation therapy and/or steroids for pain control during the active phase.
• Previous treatment with chemotherapy for mCRPC, or chemotherapy for any reason within 12 months prior to registration. (Chemotherapy in the adjuvant setting or for hormone-sensitive prostate cancer is permitted, as long as it was completed more than 6 months before registration).
• History of radiation therapy, either via external beam or brachytherapy within 28 days prior to registration.
• Systemic therapy with strontium-89, samarium-153, rhenium-186 or rhenium-188 for the treatment of bony metastases within previous 24 weeks
• Use of opioid analgesics for cancer-related pain such as oxycodone, morphine or methadone. Weak opioid analgesics such as codeine or tramadol are permitted.
• Use of experimental drug within 4 weeks of treatment.
• Patients with an intact prostate AND urinary obstructive symptoms are excluded (which includes patients with urinary symptoms from benign prostatic hyperplasia (BPH).
• Patients receiving anticoagulation therapy with warfarin are not eligible for study. Patients on other anticoagulants such as rivaroxaban, dabigatran, apixaban are permitted.
• Symptomatic nodal disease, i.e. scrotal, penile or leg edema.
• Poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease, or active, uncontrolled infection or a disease that may compromise safety. Examples include, but are not limited to, diabetes, heart failure, chronic obstructive pulmonary disease (COPD), ulcerative colitis, or Crohn's disease, Paget's disease, ventricular arrhythmia, recent (within 12 months) myocardial infarction, thromboembolic events or any psychiatric disorder that prohibits obtaining informed consent. Any medical intervention, any other condition, or any other circumstance which, in the opinion of the investigator, could compromise adherence with study requirements or otherwise compromise the study's objectives.
• Evidence of disease in sites or extent that, in the opinion of the investigator, would put the patient at risk from therapy with testosterone (e.g. femoral metastases with concern over fracture risk, severe and extensive spinal metastases with concern over spinal cord compression, etc). Patients with low volume visceral metastasis are permitted at the discretion of the investigator, however bone disease must be predominant.

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Condition: Castration-Resistant Prostate Carcinoma, Metastatic Prostate Adenocarcinoma, Stage IVB Prostate Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06039371

Sponsor: University of Washington

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

• Must be willing to provide informed consent prior to any study specific procedures
• Age >= 18 years
• Documented histologically confirmed adenocarcinoma of the prostate
• Patient must have evidence of castration resistant prostate cancer as evidenced by PSA progression (per Prostate Cancer Working Group 3 [PCWG3] criteria) and a castrate serum testosterone level (i.e., =< 50 mg/dL)
• PSA must be at least 2 ng/ml and rising on two successive measurements at least two weeks apart
• Patients must have progressed on at least one prior next-generation androgen receptor-signalling inhibitor (e.g., abiraterone, enzalutamide, etc.). There must be at least a 2-week washout period after stopping the most recent approved therapy for metastatic castration-resistant prostate cancer (mCRPC) (e.g., abiraterone, enzalutamide, Ra-223, sipuleucel-t) prior to cycle 1, day 1. If applicable, patients should be weaned off steroids at least 1 week prior to starting treatment
• No prior chemotherapy for the treatment of mCRPC. Patients may have received docetaxel for the treatment of hormone-sensitive prostate cancer
• Prior treatment with non-chemotherapy investigational agents is permitted. There must be at least a 2-week washout period after stopping any investigational cancer agent prior to cycle 1, day 1
• Hemoglobin >= 9 g/dL with no blood transfusion in the past 28 days (within 30 days prior to administration of study treatment)
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (within 30 days prior to administration of study treatment)
• Platelet count >= 100 x 10^9/L (within 30 days prior to administration of study treatment)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 30 days prior to administration of study treatment)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be =< 5x ULN (within 30 days prior to administration of study treatment)
• Patients must have creatinine clearance estimated using the Cockcroft-Gault equation or based on 24 hour urine test of >= 51 mL/min (within 30 days prior to administration of study treatment)
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Patients must have a life expectancy >= 16 weeks
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
• At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by CT, positron emission tomography (PET), magnetic resonance imaging (MRI) and/or bone scan and is suitable for repeated assessment
• Must be willing to undergo metastatic biopsy and have a lesion amenable for biopsy
• Male patients and their partners, who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination, throughout the period of taking study treatment and for 6 months after last dose of study drug(s) to prevent pregnancy in a partner

Exclusion Criteria:

• Involvement in the planning and/or conduct of the study
• Other malignancy unless curatively treated with no evidence of disease for >= 2 years except: adequately treated non-melanoma skin cancer, non-muscle invasive bladder cancer
• Persistent toxicities (Common Terminology Criteria for Adverse Event (CTCAE) grade > 2) caused by previous cancer therapy, excluding alopecia
• Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
• Use of corticosteroids at a dose equivalent to > 10 mg of prednisone daily
• Planning to receive concurrent treatment with another systemic cancer therapy, aside from a luteinizing hormone releasing hormone (LHRH) analogue
• Use of warfarin is not permitted. Low-molecular weight heparin and direct oral anticoagulants are allowed, but their use should be discussed with the principal investigator (PI) first
• Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, history of prior myocardial infarction, uncontrolled major seizure disorder, uncontrolled hypertension (blood pressure [BP] >= 165/100), history of prior stroke, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease or any psychiatric disorder that prohibits obtaining informed consent
• Patients with a known hypersensitivity to the testosterone cypionate, etoposide, carboplatin or any of the excipients of these products
• Patients with known active hepatitis (i.e., hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids
• 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
• Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule
• Evidence of disease that, in the opinion of the investigator, would put the patient at risk from testosterone therapy (e.g. femoral metastases with concern over fracture risk, spinal metastases with concern over spinal cord compression, lymph node disease with concern for ureteral obstruction)
• Patients with pain attributable to their prostate cancer.
• Excluded due to concern for pain flare due to testosterone supplementation
• Tumor causing urinary outlet obstruction that requires catheterization for voiding. Patients that require catheterization to void secondary to benign strictures or other non-cancer causes will be permitted to enroll. Patients with percutaneous nephrostomy tubes will also be permitted to enroll
• Prior history of deep venous thrombosis or pulmonary embolism within 5 years prior to enrollment in the study and not currently on systemic anticoagulation.
• Excluded due to risk of venous thromboembolism from hormone supplementation
• Patients with NYHA (New York Heart Association) class III or IV heart failure or history of a prior myocardial infarction (MI) within 5 years of enrollment to the study.
• Excluded due to increased risk of cardiovascular events with testosterone supplementation

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Condition: Metastatic Castration-resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06100705

Sponsor: Yale University

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

• Written informed consent obtained prior to the initiation of study procedures.
• Patients who meet the US FDA-approved indication for Sipuleucel-T: for asymptomatic or minimally symptomatic mCRPC at the discretion of the treating investigator.
• Histologically confirmed adenocarcinoma of the prostate.
• Metastatic disease as evidenced by soft tissue and/or bony metastases on baseline bone scan and/or computed tomography (CT) scan or Magnetic Resonance Image (MRI).
• Progressive castration-resistant prostate cancer (CRCP): Participants must have current or historical evidence of disease progression concomitant with surgical or medical castration and during immediate past systemic therapy, as demonstrated by (a) PSA progression, or (b) progression of measurable disease, or (c) progression of non-measurable disease as defined below: 1. By PSA: two consecutively rising PSA values, at least 7 days apart, each ≥ 1.0 ng/mL and ≥ 50% above the minimum PSA observed during castration therapy or above the pre-treatment value if there was no response. 2. By measurable disease: Progressive disease by RECIST v1.1 criteria 3. By non-measurable disease i. Soft tissue disease: The appearance of 1 or more new lesions, and/or unequivocal worsening of non-measurable disease when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response. ii. Bone disease: Appearance of 2 or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response. Increased uptake of pre-existing lesions on bone scan does not constitute progression.
• Castration status confirmed by serum testosterone level <50ng/dL
• ECOG Performance Status of 0 or 1.
• Adequate liver function: 1. Bilirubin <2.0 x institutional upper limit of normal (UNL) 2. AST (SGOT) <2.5 x UNL 3. ALT (SGPT) <2.5 x UNL
• Acceptable renal function a) Serum creatinine <2.0 x UNL
• Acceptable hematologic function: 1. Absolute neutrophil count (ANC) > 1.0 x10^9 cells /L) 2. Platelet counts > 100 x 10^9 / L) 3. Hemoglobin >9 g/dL

Exclusion Criteria:

• PSA >20ng/dL within the 4 weeks prior to signing ICF
• Previously treated with three or more FDA-approved androgen/AR signaling inhibitors (ASI) (e.g., abiraterone, enzalutamide, apalutamide, darolutamide). No minimum number of ASI is required.
• Prior chemotherapy for mCRPC. However, prior chemotherapy administered for mCSPC is allowed unless the disease progression to CRPC occurred within 12 months from the last dose of chemotherapy.
• Prior treatment with Sipuleucel-T or supraphysiologic dose of testosterone treatment for prostate cancer.
• Prior systemic treatment with ASI, PARP inhibitor or Radium-223 or other systemic anti-cancer therapy for prostate cancer within 4 weeks prior to eligibility confirmation.
• Prior prednisone >10mg (or its equivalent) within 2 weeks prior to registration.
• Prior immunotherapy or Lu177 PSMA radioligand therapy within 6 weeks prior to registration.
• Prior palliative radiotherapy within 2 weeks prior to registration.
• Radiographic evidence of hepatic metastases
• Use of narcotics including tramadol or stronger for cancer-related pain within 4 weeks prior to signing ICF. Use of NSAIDs or acetaminophen is allowed.
• Active autoimmune disease requiring systemic corticosteroids of prednisone greater than 10mg a day or the equivalent dose of other corticosteroids.
• Known active HIV, Hepatitis B or Hepatitis C or Human T cell Lymphotropic virus (HTLV)-1 infection. Testing is not required. Note: Participants with resolved, historic HIV, Hepatitis B or Hepatitis C or Human T cell Lymphotropic virus (HTLV)-1 will be assessed by the PI and deemed eligible if their viral infections are in remission: without detectable viruses and secondary immunodeficiency, and without requiring any treatments that affects immune function. Eligibility will be determined after a discussion with the PI and adequate standard clinical tests are acquired to prove that they are in remission.
• Active infection requiring parenteral antibiotic therapy or causing fever (temperature >100.5 in Fahrenheit scale) within 1 week prior to registration.
• Life expectancy of less than 6 months prior to signing ICF.
• Any medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence with study requirements or otherwise compromise the study's objectives.

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Condition: Castration-Resistant Prostate Carcinoma, Metastatic Prostate Carcinoma, Stage IVB Prostate Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06305598

Sponsor: Roswell Park Cancer Institute

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

• Age ≥ 18 years of age
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Histologically confirmed carcinoma of the prostate
• Progressing on continuous androgen ablative therapy (either surgical castration or LHRH agonist)
• Documented castrate level of blood testosterone (< 50 ng/dL)
• Patients must have progressed on prior treatment with at least one Androgen Receptor Signaling Inhibitors (ARSI) and at least one chemotherapy (by prostate specific antigen [PSA] criteria or radiographically)
• Have biopsiable disease (a fresh biopsy is not required at baseline if adequate archival tissue is available)
• Absolute neutrophil count: ≥1,200/µL
• Platelets: ≥ 100,000/µL
• Total bilirubin: ≤ 1.2 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/ Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]): ≤ 3 × institutional ULN
• Creatinine clearance (CrCl) > 50 mL/min (Cockcroft-Gault equation)
• Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present
• Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

• Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• Greater than 5 sites of visceral disease in lung or liver (nonspecific lung nodules ≤ 1 cm in diameter is permitted)
• Evidence of disease in sites or extent that, in the opinion of the investigator, would put the patient at risk from therapy with testosterone (e.g., femoral metastases with concern over fracture risk, spinal metastases with concern over spinal cord compression, lymph node disease with concern for ureteral obstruction)
• Active uncontrolled infection, including known history of acquired immunodeficiency syndrome (AIDS) or hepatitis B or C
• Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule
• Prior history of a thromboembolic event within the last 12 months and not currently on systemic anticoagulation
• Hematocrit > 50%, untreated severe obstructive sleep apnea, uncontrolled or poorly controlled heart failure (per Endocrine Society Clinical Practice Guidelines)
• 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
• Known allergy to testosterone cypionate or any of its excipients
• Unwilling or unable to follow protocol requirements
• Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study drug

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Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06594926

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. Histologically confirmed adenocarcinoma of the prostate
2. ≥18 years of age
3. ECOG performance status 0-1
4. PSA progression while on darolutamide defined as three rising PSA (1 baseline and 2 consecutive rises) levels at least 1 week apart despite castrate testosterone level (<1.7nmol/L).
5. AJCC stage M0 on conventional imaging.
6. Previous PSMA PET only M1 disease in the hormone-sensitive setting that is now M0 CRPC on conventional imaging following >18 months of ADT + darolutamide are eligible.
7. Nodes up to 2cm in short-axis in pelvis are permitted
8. PSA >1.0 ng/mL during screening
9. Serum testosterone <1.7nmol/L and on an LHRH agonist/antagonist
10. Adequate bone marrow function (platelets > 100 x 109/L, ANC > 1.5 x 109/L, Hb >90)
11. Adequate liver function (ALT or AST < 2.5 x ULN, bilirubin < 1.5 x ULN)
12. Adequate renal function (creatinine <1.5 x ULN)
13. Willingness and ability to comply with study requirements, including treatment and timing of treatment.

Exclusion Criteria:

1. Life expectancy <3 months.
2. Neuroendocrine or small cell prostate cancer on any prior diagnostic tissue sample.
3. Metastatic prostate cancer on conventional imaging (WBBS or CT scan) at any point in disease course (except for pathological nodes up to 2cm in short axis in the pelvis).
4. Current or prior treatment with enzalutamide, abiraterone, apalutamide, or cytotoxic chemotherapy. Prior first generation ARSI such as bicalutamide, flutamide, nilutamide are permitted.
5. Current or pre-existing cardiac or thromboembolic risk factors, including but not limited to: i. Prior myocardial infarction, or unstable angina within 24 months of study entry, ii. Uncontrolled or symptomatic cardiac disease including, but not limited to angina, dyspnoea on exertion, orthopnoea; cardiac failure (NYHA classification 3-4) or uncontrolled arrhythmias. iii. Significant co-morbidities that increase cardiovascular risk, including significant hypertension (Baseline systolic BP>160 or diastolic BP>100 despite optimal treatment) that are uncontrolled, as assessed by the treating oncologist.
6. Another malignancy diagnosis within 2 years before registration. Participants with a history of treated carcinoma in situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or non-muscle invasive urothelial carcinoma of the bladder are eligible if malignancy has been treated with curative intent. Participants with a history of other malignancies are eligible if they have been continuously disease-free for at least 2 years after definitive primary treatment or the chance of recurrence is sufficiently low as to be very unlikely to affect study outcomes according to the treating local oncologist.
7. Concurrent illness that could preclude the participant's ability to participate in the study and follow protocol with reasonable safety.
8. Planned ongoing drug Interactions as per protocol section 5.2.4 that are considered unable to be managed prior to study registration.
9. Radiation therapy within the previous 4 weeks (participants are permitted to have SBRT to PSMA PET only disease prior to study enrolment if they continue on darolutamide. Note that if the metastases are visible on conventional imaging at the time of radiation treatment the participant is not eligible).

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Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04631744

Sponsor: Weill Medical College of Cornell University

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

• 1. Age >18 years. 2. Documented histological or cytological diagnosis of prostate carcinoma. 3. Evidence of metastatic PC on imaging (bone scan and/or CT/MRI scan)
• Patients with liver metastases must have biopsy proven evidence of metastatic prostate cancer in the liver. 4. Agree to undergo a biopsy of at least one metastatic site or primary prostate prior to beginning therapy. Adequate archival metastatic tissue can be used if available in lieu of a biopsy if done when patient had CRPC and within 6 months of the start of treatment. 5. Agree to undergo a biopsy of at least one metastatic site or primary prostate after 3 weeks of therapy (biopsy must be between day 21 and day 24 of treatment). Re-biopsy of same pre-treatment biopsy soft tissue site especially liver metastases is preferred. 6. Serum testosterone level less than 50 ng/dl. Subjects without prior orchiectomy must be currently taking and willing to continue luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist) therapy until permanent discontinuation of study treatment. 7. Documented progressive metastatic CRPC based on at least one of the following criteria:
• PSA progression according to Prostate Cancer Working Group 3 (PCWG3) criteria
• Objective radiographic progression, according to PCWG3 criteria 8. ECOG performance status of 0-1 9. Recovery to baseline or ≤ Grade 1 CTCAE v4 from toxicities related to any prior treatments, unless specified below or AE(s) are clinically nonsignificant and/or stable on supportive therapy. 10. Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment:
• Absolute neutrophil count (ANC) ≥ 1500/mm^3 (≥ 1.5 GI/L) without granulocyte colony-stimulating factor support
• White blood cell count ≥ 2500/mm^3 (≥ 2.5 GI/L)
• Platelets ≥ 100,000/mm^3 (≥ 100 GI/L) without transfusion
• Hemoglobin ≥ 9 g/dL (≥ 90 g/L)
• Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert's disease ≤ 3 x ULN)
• Serum albumin ≥ 2.8 g/dl
• Serum creatinine ≤ 2.0 x ULN or calculated creatinine clearance ≥ 30 mL/min (≥ 0.5 mL/sec) using the Cockcroft-Gault equation:
• If urine dipstick is positive, then: Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol) 11. Patients without liver metastases must have evidence of amplification or activating mutation of selected targets of cabozantinib (including MET, KIT, RET, VEGFR-1, VEGFR-2, VEGFR-3, FLT3, AXL, TRKB, or TIE2) by at least one of the following:
• DNA sequencing of metastatic tumor biopsy specimen or cfDNA test
• RNA sequencing of metastatic tumor biopsy specimen
• Commercial cell-free DNA assay
• Overexpression by IHC on metastatic tumor biopsy specimen 12. Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment 13. Capable of understanding and complying with the protocol requirements and must have signed the informed consent document

Exclusion Criteria:

• 1. Prior treatment with cabozantinib 2. Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment. 3. Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) except agents to maintain castrate status within 4 weeks before first dose of study treatment. Antiresportive bone agents are also allowed. 4. Subject has received abiraterone acetate or enzalutamide within 2 weeks before enrollment. 5. Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible. 6. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment for neurological indications at the time of first dose of study treatment. 7. Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor. 8. The subject has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.3 x the laboratory ULN within 14 days before the first dose of study treatment. 9. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
• Uncontrolled hypertension defined as sustained blood pressure (BP) >140 mm Hg systolic or >90 mm Hg diastolic despite optimal antihypertensive treatment.
• Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g. deep venous thrombosis, pulmonary embolism) within 6 months before first dose.
• Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
• The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
• Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose.
• Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 mL) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose.
• Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
• Lesions invading or encasing any major blood vessels. Subjects with lesions invading the intrahepatic vasculature, including portal vein, hepatic vein, and hepatic artery, are eligible.
• Other clinically significant disorders that would preclude safe study participation.
• Serious non-healing wound/ulcer/bone fracture.
• Uncompensated/symptomatic hypothyroidism.
• Moderate to severe hepatic impairment (Child-Pugh B or C). 10. Major surgery (e.g., GI surgery, removal or biopsy of brain metastasis) within 8 weeks before first dose of study treatment. Complete wound healing from major surgery must have occurred 1 month before first dose and from minor surgery (e.g. simple excision, tooth extraction) at least 10 days before first dose. Subjects with clinically relevant ongoing complications from prior surgery are not eligible. 11. Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment [add reference for Fridericia formula]. Note: If a single ECG shows a QTcF with an absolute value > 500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility. 12. Inability to swallow tablets. 13. Previously identified allergy or hypersensitivity to components of the study treatment formulations. 14. Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy. Molecular Eligibility To be eligible, a patient's tumor must have evidence of gene amplification, an activating mutation, or overexpression of one of the following genes: MET, KIT, RET, VEGFR-1, VEGFR-2, VEGFR-3, FLT3, AXL, TRKB, or TIE2. Eligibility can be met via the following diagnostic tests: 1. DNA sequencing of a metastatic tumor biopsy specimen showing gene amplification or activating mutation using a CLIA-certified assay. Tumor tissue samples must have been collected within 6 months of enrollment. 2. Protein overexpression in a metastatic tumor biopsy specimen determined by immunohistochemistry (IHC) showing 2+ or 3+ protein expression using a CLIA-certified assay.These include common in-house KIT and commercial reference labs for panTRK (e.g. NeoGenomics) and cMET (e.g. NeoGenomics, Caris, Mayo Clinic). 3. CLIA-certified commercial cell free DNA assay reporting gene amplification or activating mutation within 3 months of enrollment.
• For the Guardant360 Liquid Biopsy amplification must be at least (++) or (+++) for to meet eligibility.
• For the FoundationOneLiquid assay, amplification will be eligible. Reports that have an "equivocal" or "subclonal" designation will not be eligible. 4. Any non-CLIA certified assay such as RNA expression profiling of a metastatic tumor biopsy specimen showing overexpression must be confirmed by a CLIA-certified assay (i.e., immunohistochemistry showing 2+ or 3+ protein expression) Patients who do not meet molecular

Eligibility Criteria:

1. will be allowed to enroll if they have liver metastases that meet RECIST criteria for measurable disease. Patients with prostate adenocarcinoma or Neuroendocrine prostate cancer (NEPC) will be allowed to enroll.

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Condition: Castration-resistant Prostate Cancer, Metastatic Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05502315

Sponsor: Rana McKay, MD

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

• Subjects must meet all of the following applicable inclusion criteria to participate in this study:
• Willing and able to provide, or have a legally authorized representative provide, written informed consent and HIPAA authorization for the release of personal health information. A signed informed consent must be obtained before screening procedures are performed. NOTE: HIPAA authorization may be either included in the informed consent or obtained separately.
• Males 18 years of age and above.
• Histological or cytological proof of prostate adenocarcinoma or mixed adenocarcinoma/neuroendocrine tumors. Pure small cell of the prostate is not allowed.
• ECOG status of ≤ 2
• Progressive mCRPC as defined: 1) castrate levels of serum testosterone < 50 ng/dL AND 2) progressive disease as defined by PSA or radiographic progression. Subjects with measurable and non-measurable disease (i.e., bone only metastases) are allowed. NOTE: ENROLLMENT of subjects with non-measurable disease (i.e., bone only metastases) will be capped at 50% of enrollment target (n=25).
• Must have exposure to one prior taxane (or be taxane ineligible or refuse taxane) AND one prior AR-targeting agent (for example, abiraterone, enzalutamide, apalutamide, darolutamide). Receipt of taxane or AR-targeting agent may be in the hormone sensitive or castration resistant setting. Subjects may have received more than 1 prior Androgen receptor signaling inhibitors (ARSI). Subjects may have had prior 177Lu-PSMA-617.
• Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
• Normal organ function with acceptable initial laboratory values within 14 days of treatment start:
• WBC: ≥ 2,500/mcL
• ANC: ≥ 1,500/mcL
• Hemoglobin: ≥ 9 g/dL (transfusions are permitted)
• Platelet count: ≥ 100,000/mcL
• Serum creatinine or calculated Creatinine Clearance: Serum creatinine ≤ 1.5 x ULN or calculated CrCl ≥ 30 mL/min as defined by Cockcroft-Gault equation
• Total Bilirubin: ≤ 1.5 x ULN (≤ 3 x ULN for subjects with documented Gilbert's disease)
• SGOT (AST): ≤ 3 x ULN
• SGPT (ALT): ≤ 3 x ULN
• Alkaline Phosphatase (ALP): ≤ 5 x ULN with documented bone metastases
• Serum Albumin: ≥ 2.8 g/dL
• Urine protein/creatinine ratio (UPCR): ≤ 2 mg/mg (≤ 113.2 mg/mmol), or 24-h urine protein ≤ 2 g
• Subjects must agree to use a medically acceptable method of birth control as outlined in the protocol
• HIV-positive with negative viral loads on stable antiretroviral regimen will be considered eligible. Subjects must have CD4 count > 350.

Exclusion Criteria:

• Subjects meeting any of the criteria below may not participate in the study:
• Disease progression on prior checkpoint inhibitor treatment.
• Prior cabozantinib.
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
• Receipt of any type of cytotoxic, biologic or investigational systemic anti-cancer agent within 4 weeks before first dose of study treatment.
• Treatment with abiraterone, apalutamide, or darolutamide within 2 weeks of treatment initiation. Treatment with investigational prostate cancer directed therapy within 4 weeks of treatment initiation. Treatment with enzalutamide within 4 weeks of treatment initiation.
• Receipt of more than 1 line of chemotherapy (including both hormone sensitive and CRPC). First-generation anti-androgen use (such as bicalutamide) will not be tabulated as a line of therapy.
• Administration of a live, attenuated vaccine within 30 days prior to first dose of study treatment.
• Active autoimmune disease or condition requiring prednisone >10 mg daily (or equivalent). Physiologic replacement is permitted. Topical, ocular, intra-articular steroids or inhaled corticosteroids are permitted.
• Imminent or established spinal cord compression based on clinical and/or imaging findings.
• Radiation therapy within 1 week of study treatment start.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment.
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
• Malabsorption syndrome.
• Requirement for hemodialysis or peritoneal dialysis.
• History of solid organ or allogenic stem cell transplant.
• Active hepatitis B/C or positive TB test with active mycobacterial infection requiring systemic treatment.
• Active treatment (within 5 days of registration) with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose molecular weight heparins (LMWH).
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
• Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment.
• Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose of study treatment.
• Subjects with a diagnosis of incidental, subsegmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation (see exclusion criterion above) for at least 1 week before first dose of study treatment.
• Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation
• The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
• Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment.
• Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5ml) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose of study treatment.
• Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
• Lesions invading or encasing any major blood vessels.
• Other clinically significant disorders that would preclude safe study participation.
• Serious non-healing wound/ulcer/bone fracture.
• Uncompensated/symptomatic hypothyroidism.
• Moderate to severe hepatic impairment (Child-Pugh B or C).
• Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 2 weeks before first dose of study treatment. Minor surgeries within 10 days before first dose of study treatment. Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
• Corrected QT interval calculated by Fridericia formula (QTcF) >500 ms per electrocardiogram (ECG) within 14 days before first dose of study treatment [add reference for Fridericia formula]. NOTE: If a single ECG shows a QTcF with an absolute >500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility.
• Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer or superficial bladder cancer.
• Known allergy to any of the compounds under investigation.
• Inability to swallow tablets.

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Condition: Metastatic Castration-resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05613894

Sponsor: University of Utah

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

• Male subject aged ≥ 18 years.
• Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology.
• Prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (<50 ng/dL or <1.7 nmol/L).
• Prior treatment with at least one prior Novel Hormone Therapy (NHT), defined as second-generation anti-androgen therapies that include, but are not limited to, abiraterone acetate, enzalutamide, apalutamide, and darolutamide.
• Must have been previously treated with at least 2 cycles of a taxane containing regimen (such as docetaxel or cabazitaxel).
• ≥ 1 PSMA-positive lesion and/or metastatic disease that is predominantly PSMA positive and with no dominant PSMA-negative metastatic lesion.
• Must have progressive mCRPC per the treating investigator.
• ECOG Performance Status ≤ 1.
• Adequate organ function as defined as:
• Hematologic:
• Absolute neutrophil count (ANC) ≥ 1500/µL without granulocyte colony-stimulating factor support
• White blood cell count ≥ 3000/µL.
• Platelet count ≥ 100,000/µL
• Hemoglobin ≥ 9g/dL
• Serum albumin ≥ 2.5 g/dl
• PT/INR or partial thromboplastin time (PTT) test < 1.3x the laboratory ULN
• Hepatic:
• Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN)
• For subjects with Gilbert's disease: ≤ 3x ULN
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3x upper limit of normal (ULN).
• Renal:
• Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol), or 24-h urine protein ≤ 1 g
• Estimated creatinine clearance ≥ 30 mL/min by Cockcroft-Gault formula
• Sexually active fertile patients and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 6 months after the last dose of study treatment in accordance with section 5.4.2.
• Recovery to baseline or ≤ Grade 1 CTCAE v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
• Patients must have a life expectancy >3 months.

Exclusion Criteria:

• Receiving other investigational anti-cancer agents.
• Prior treatment with cabozantinib
• Previous treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or hemi-body irradiation within 6 months prior to randomization.
• Previous PSMA-targeted radioligand therapy
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
• Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
• Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment.
• Systemic treatment with radionuclides within 6 weeks before first dose of study treatment.
• Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
• Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis).
• Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment.
• Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment.
• Major surgery within 4 weeks prior to starting study drug, minor surgery within 10 days, or subjects who have not fully recovered from major surgery.
• Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%), such as locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the breast.
• Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH)
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class III or IV, unstable angina pectoris, serious cardiac arrhythmias.
• Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic events, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 6 months before the first dose of study treatment.
• Subjects with a diagnosis of incidental, subsegmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation (see exclusion criterion 14) for at least 1 week before first dose of study treatment.
• Uncontrolled hypertension defined as sustained blood pressure (BP) ≥ 150 mm Hg systolic or >90 mmHg diastolic despite optimal antihypertensive treatment.
• Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
• The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
• Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment.
• Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment.
• Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc.)
• Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose of study treatment.
• Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
• Lesions invading or encasing any major blood vessels
• Other clinically significant disorders that would preclude safe study participation.
• Serious non-healing wound/ulcer/bone fracture.
• Uncompensated/symptomatic hypothyroidism.
• Moderate to severe hepatic impairment (Child-Pugh B or C).
• Known history of COVID-19 unless the subject has clinically recovered from the disease at least 30 days prior to first dose of study treatment.
• Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 2 weeks before first dose of study treatment or minor surgeries within 10 days before first dose of study treatment.
• Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. --Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
• Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms per electrocardiogram (ECG) within 14 days before first dose of study treatment. --Note: If a single ECG shows a QTcF with an absolute value > 500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility.
• Inability to swallow tablets
• Previously identified allergy or hypersensitivity to components of the study treatment formulations.
• Known HIV infection with a detectable viral load within 6 months of the anticipated start of treatment. --Note: Subjects on effective antiretroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial.
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), or hepatitis C.
• Note: Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• Medical, psychiatric, cognitive, or other conditions that may compromise the subject's ability to understand the subject information, give informed consent, comply with the study protocol or complete the study.
• Subjects taking prohibited medications as described in Section 6.8.2. A washout period of prohibited medications for a period of at least five half-lives or as clinically indicated should occur before the start of treatment.

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Condition: Castration Resistant Prostate Cancer, Castration Sensitive Prostate Cancer, Prostate Adenocarcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05919329

Sponsor: OHSU Knight Cancer Institute

Phase: Phase 4

Eligibility:

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

Inclusion Criteria:

• Participant or legally authorized representative (LAR) must provide written informed consent before any study-specific procedures or interventions are performed.
• Participants must have confirmed prostate adenocarcinoma, histologically, or by combined imaging and biochemical markers.
• Age >= 18 years. Given the nature of the disease in question, only men will be included. Members of all races and ethnic groups will be included.
• Participants must have sites of prostate cancer showing uptake on an initial PSMA PET scan.
• Participants are planned to receive hormonal therapy within eight weeks of the initial PSMA PET. The hormonal therapy agents include:
• For CSPC: GnRH agonists, GnRH antagonists, first-generation antiandrogen (e.g. bicalutamide), or androgen receptor (AR)-targeted agent (e.g. Abiraterone, Enzalutamide, Apalutamide, Darolutamide)
• For CRPC: this group of patients are typically on continuous ADT (GnRH agonists or antagonists), which will be continued, and the hormonal therapy they will be started on is an androgen receptor (AR)-targeted agent (e.g. Abiraterone, Enzalutamide, Apalutamide, Darolutamide)
• Life expectancy > 3 months.
• Cohort 1: Castration resistant prostate cancer with rising PSA (confirmed by two PSA values at least 1 week apart), testosterone < 50 ng/dL, on continuous ADT at least 4 months, no AR targeted agent in the prior 4 months.
• Cohort 2: Castration sensitive prostate cancer with no ADT or AR targeted agents use in the past 12 months, testosterone >50 ng/dL

Exclusion Criteria:

• Uncontrolled serious infection.
• Intercurrent illness or condition that would limit compliance with study requirements.
• Participants who have undergone any cancer treatment other than the hormonal therapy (systemic or radiation therapy) or who have started any supplements or herbal medications intended to treat cancer between the baseline PSMA PET and PSMA PET at day 28.

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Condition: Prostate Cancer

Study Type: Observational [Patient Registry]

Clinical Trials Identifier NCT 8-digits: NCT06494696

Sponsor: Chang Gung Memorial Hospital

Phase:

Eligibility:

• Age: minimum 40 Years maximum 85 Years
• Gender: Male

Inclusion Criteria:

1. Patients who indicated MRI of pelvis due to clinical suspicion of prostate cancer based on elevated PSA (4~20 ng/mL), abnormal digital rectal examination or lower urinary tract syndromes.
2. Males aged between 40 and 85 years with a life expectancy greater than two years.
3. Naïve to prostate biopsy in the past.
4. Assessment of daily physical status graded 0 to 2 based on the Eastern Cooperative Oncology Group (ECOG) criteria.
5. Willing to sign the informed consent.

Exclusion Criteria:

1. Unable to tolerate the PET/MRI scan, such as those with claustrophobia, unable to lie still, consciousness unclear, vital sign unstable, or having MRI unsafe metallic implants or devices.
2. With renal impairment (glomerular filtration rate lower than 30 ml/min/1.73 m2), and allergy to medium contrast.
3. High risk to conduct examination after evaluations of PI
4. Patient had previous malignancy history

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Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06171269

Sponsor: University of Chicago

Eligibility:

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

Inclusion Criteria:

• Adult (≥ 18 years old) male patients with an ECOG Performance Status 0-2
• Histologically-confirmed, MRI-visible prostate adenocarcinoma with NCCN intermediate- or high-risk disease1 without extra-pelvic metastasis.

Exclusion Criteria:

• Distant metastases
• Prior active treatment for prostate cancer including radical prostatectomy, high-intensity focused ultrasound (HIFU), cryosurgery, ADT, or cytotoxic chemotherapy for treatment of prostate cancer. Patients with prostate cancer on active surveillance prior to the study are not excluded if they have not received active treatment.
• Prior pelvic radiotherapy including brachytherapy.
• Additional active concurrent malignancies (except localized cutaneous squamous or basal cell carcinomas).
• Comorbid conditions that, in the opinion of the treating radiation oncologist, preclude the patient from safely receiving the protocol-specified treatment including RT and/or ADT.
• Patients with contraindications to MRI including patients with ferromagnetic materials in their body (e.g. bioimplants, surgical hardware, shrapnel), patients who are unable to receive contrast due to history of allergy or impaired renal function (glomerular filtration rate < 30 mil/min), and patients unable to tolerate MRI for other reasons (e.g. significant claustrophobia).
• Patients for whom hydrogel or hyaluronic acid spacer will be placed.
• Patients incapable of giving informed consent.
• Patients who are unable to adhere to the experimental protocols for any reason.

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Condition: Metastatic Castration-resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06480110

Sponsor: Rigshospitalet, Denmark

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

• 1. Have a histologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate (carcinomas with pure small-cell histology or pure high grade neuroendocrine histology are excluded; neuroendocrine differentiation is allowed). 2. Surgically or medically castrated, with serum testosterone levels of ≤ 50 ng/dL equivalent to 1.7 nmol/L. For patients, currently being treated with luteinizing hormone-releasing hormone (LHRH) agonists, i.e., patients who have not undergone an orchiectomy, therapy must be continued throughout the study. 3. Have evidence of disease progression after prior therapy for mCRPC: Disease progression after initiation of most recent therapy is based on any of the following criteria:
• Rise in PSA: a minimum of 2 consecutive rising levels, with an interval of ≥ 1 week between each determination. The most recent screening measurement must have been ≥ 2 ng/mL
• Transaxial imaging: new or progressive soft tissue masses on CT or MRI scans as defined by RECIST 1.1
• Radionuclide bone scan: at least 2 new metastatic lesions 4. Signed informed consent obtained prior to initiation of any study-specific procedures or treatment 5. Age ≥ 18 years 6. Life expectancy ≥ 3 months 7. Performance status 0
• 1 8. Adequate organ functions 1. Hematological: absolute neutrophil count (ANC) >1.5 x 109/L, platelet count >100 x 109/L, hemoglobin > 6,2 mmol/L 2. Hepatic: Bilirubin within normal range, aspartate transaminase (AST) and alanine transaminase (ALT) <2.5 upper normal lever, albumin > 25 g/L 3. Renal: creatinine clearance >30 mL/min/1.73m2

Exclusion Criteria:

• 1. History of significant gastric or small bowel resection, malabsorption syndrome, or other lack of integrity of the upper gastrointestinal tract that may prevent compliance with oral drug administration 2. Presence of any serious concomitant systemic disorders and/or psychiatric condition incompatible with the study (at the investigator's discretion) 3. Presence of any active infection (at the investigator's discretion). 4. Central nervous system (CNS) disease including epilepsy or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures. 5. Concurrent use of cationic amphiphilic drugs (see appendix A) including over-the-counter medication. 6. Use of other investigational drug 7. Allergic reaction to any of the included drugs

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