Clinical Trials

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Positron Emission Tomography Using 64Cu-SAR-bisPSMA in Participants With High-risk Prostate Cancer Prior to Radical Prostatectomy: A Prospective, Single-arm, Multi-center, Blinded-review, Phase 3 Diagnostic Performance Study


Condition: Prostate Cancer, Prostatic Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06056830

Sponsor: Clarity Pharmaceuticals Ltd

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • At least 18 years of age.
  • Signed informed consent.
  • Untreated, histologically confirmed adenocarcinoma of the prostate.
  • High-risk or greater PC defined by National Comprehensive Cancer Network Guidelines Version 1.202327 (clinical stage ≥T3a, or Grade Group ≥4, or PSA >20 ng/mL).
  • Patients electing to undergo RP with PLND.

Exclusion Criteria:

  • Administration of any high energy (>300 KeV) gamma-emitting radioisotope within 5 physical half-lives prior to Day 1.
  • Known or expected hypersensitivity to 64Cu-SAR-bisPSMA or any of its components.
  • Patients with known predominant small cell or neuroendocrine PC.

View trial on ClinicalTrials.gov


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PD-1 and PD-L1 have had a significant clinical impact as an immunotherapy target for patients with multiple genitourinary malignancies, including bladder and renal cancers. We continue to find new settings and novel combinations for the use of the antibodies that target these checkpoints for our patients with genitourinary cancers. For example, just a few weeks ago, at ASCO GU 2024, we saw the data release from the AMBASSADOR randomized phase 3 clinical trial, offering supportive data for the use of pembrolizumab for adjuvant therapy for those with high-risk features after radical cystectomy for muscle invasive urothelial bladder cancer.1 However, there is still an urgent need to identify new immunotherapy targets and develop new therapies to manipulate those targets.
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A Phase 1/2, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SNS-101 (Anti VISTA) as Monotherapy and in Combination With Cemiplimab in Patients With Advanced Solid Tumors


Condition: Solid Tumor, Adult, Advanced Solid Tumor, Head and Neck Cancer, Breast Cancer, Colon Cancer, Pancreatic Cancer, Gastric Cancer, Esophageal Cancer, Prostate Cancer, Uterine Cancer, Cervix Cancer, Ovarian Cancer, Kidney Cancer, Bladder Cancer, Thyroid Cancer, Melanoma, Sarcoma, Advanced Cancer, Metastatic Cancer, Refractory Cancer, Non Small Cell Lung Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05864144

Sponsor: Sensei Biotherapeutics, Inc.

Phase: Phase 1/Phase 2

Eligibility:

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

Key Inclusion Criteria:

  • Histologically or cytologically documented locally advanced, unresectable or metastatic solid tumor.
  • Having received and failed or was intolerant to standard of care for advanced disease or not eligible for standard of care therapy with the following tumor types for patients in Phase 1 dose expansion cohorts: 1. Microsatellite Stable (MSS) CRC (both monotherapy and combination cohorts); no more than 3 lines of prior systemic therapy for metastatic disease. 2. H&N cancer (combination cohort only); no more than 2 lines of prior systemic therapy for metastatic disease. 3. Melanoma (combination cohort only); no more than 3 lines of prior systemic therapy for metastatic disease, including at least 1 prior treatment with a BRAF inhibitor for patients with a BRAF mutation. 4. NSCLC (combination cohort only); no more than 2 lines of prior systemic therapy for metastatic disease, including at least 1 prior treatment with a targeted therapy for patients with a mutation such as EGFR, ALK, KRAS, or RET. 5. Patients with H&N cancer, melanoma, and NSCLC must not have demonstrated primary refractory disease to a prior PD-1/PD-L1 agent where the best response to that therapy was progressive disease. Additional tumor types and doses may be considered.
  • Measurable disease.
  • ECOG performance status 0 or 1.
  • Life expectancy of ≥ 3 months.
  • Willing to provide pre-treatment (archival or fresh) and on-treatment tumor biopsy samples.
  • Adequate organ function
  • Women of childbearing potential and fertile males with WOCBP partners must use highly effective contraception during the study and for 180 days after the study. Patients must agree not to donate eggs (ova, oocytes) or sperm during the study.

Key Exclusion Criteria:

  • Use of anti-PD-1/PD-L1 targeting monoclonal antibody therapy, monoclonal antibody therapy, chemotherapy, biologic, investigational, or radiotherapy within 2 weeks of Cycle 1 Day 1.
  • Clinically significant unresolved toxicities from prior anticancer therapy.
  • Grade 3 or higher immune-related adverse event on prior PD-1/PD-L1 blockade or prior agents targeting stimulatory or co-inhibitory T cell receptor.
  • Known other previous/current malignancy requiring treatment within ≤ 2 years except for limited disease treated with curative intent, such as carcinoma in situ, squamous or basal cell skin carcinoma, or superficial bladder carcinoma.
  • Known asymptomatic or symptomatic brain metastasis or leptomeningeal disease.
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
  • Women who are pregnant or breastfeeding.

View trial on ClinicalTrials.gov


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A Phase 1/2 Open-label Trial of KVA12123 Alone and in Combination With Pembrolizumab in Patients With Advanced Solid Tumors


Condition: Cancer, Solid Tumor, Melanoma, Carcinoma, Sarcoma, Lung Cancer, Prostate Cancer, Breast Cancer, Colo-rectal Cancer, Uterine Cancer, Pancreatic Cancer, Gastric Cancer, Esophageal Cancer, Thyroid Cancer, Ovarian Cancer, Kidney Cancer, Head and Neck Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05708950

Sponsor: Kineta Inc.

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  1. Willing and able to provide informed consent.
  2. Be at least 18 years of age at the time of consent.
  3. Has histologically or cytologically confirmed, locally advanced or metastatic solid tumor that has progressed or was non-responsive to standard of care therapy and for which no available curative therapy exists.
  4. Has expected survival ≥16 weeks.
  5. Presence of measurable disease by iRECIST.
  6. Has an ECOG performance status score of 0 or
  7. Has adequate organ function within 10 days prior to the start of study treatment.
  8. Has normal thyroid function or hypothyroid with stable supplementation.
  9. Has consented to the collection of archival tissue prior to study treatment initiation.
  10. Participants with prior exposure to systemic anticancer therapy including investigational agents following a 4-week washout period are eligible. Participants with prior small molecule targeted therapy or other short half-life drugs are eligible following a 2-week washout period.
  11. Participants having prior curative radiation therapy completed 2 weeks prior to study drug administration or prior palliative radiation therapy to non-CNS disease completed at least 1 week prior to study drug administration are eligible.
  12. HIV-infected participants must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease.
  13. Participants with a history of HBV infection having durable HBsAg loss and undetectable serum HBV DNA no longer requiring treatment are eligible.
  14. Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening and participants have completed curative antiviral therapy.
  15. Post-menopausal women and surgically sterile men and women are permitted.
  16. Patients of childbearing potential are permitted to participate under the following conditions:
  17. Must have negative urine pregnancy test result within 72 hrs prior to the first dose of any study drug
  18. Must agree not to become pregnant during the study and for 120 days after the final dose of any study drug
  19. Must agree not to breastfeed or donate ova, starting at time of informed consent and continuing through 120 days after the final dose of any study drug
  20. If sexually active in a way that could lead to pregnancy, must consistently use 2 acceptable methods of birth control (contraception), at least 1 of which must be highly effective starting at time of informed consent and continuing throughout the study and for 120 days after the final dose of any study drug.
  21. Patients who can father children are permitted to participate under the following conditions:
  22. Must agree not to donate sperm starting at the time of informed consent and continuing throughout the study period and for 120 days after the final dose of any study drug
  23. If sexually active with a person of childbearing potential in a way that could lead to pregnancy, must consistently use 2 acceptable methods of birth control (contraception), at least 1 of which must be highly effective starting at the time of informed consent and continuing throughout the study and for 120 days after the final dose of any study drug
  24. If sexually active with a person who is pregnant or breastfeeding, must consistently use a condom starting at time of informed consent and continuing throughout the study and for 120 days after the final dose of any study drug.
  25. Must be willing and able to comply with the trial procedures and the follow-up schedule.

Exclusion Criteria:

  1. Untreated CNS metastatic disease, leptomeningeal disease, or cord compression.
  2. Concurrent cancer other than disease under study requiring systemic treatment. Participants with basal cell or squamous cell skin cancer treated with curative intent, carcinoma in-situ of the cervix or breast treated with curative intent, RAI stage 0 Chronic Lymphocytic Leukemia, monoclonal gammopathy of undetermined significance, superficial bladder cancer or very low and low risk prostate cancer (localized Gleason score ≤ 6) under active surveillance are eligible.
  3. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
  4. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg QD of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
  5. History of (non-infectious) pneumonitis/interstitial lung disease (ILD) that required steroids or current pneumonitis/ILD.
  6. Prior treatment with VISTA-targeted therapy.
  7. Prior history of allogeneic, solid organ or stem cell transplant, or adoptive T-cell transplant.
  8. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, LAG-3, OX 40, CD137), and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE).
  9. Active known or suspected autoimmune disease that has required systemic treatment within the past year. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  10. Prior systemic anticancer therapy, including investigational agents, within 4 weeks of treatment. Participants with prior small molecule targeted therapy or other short half-life drugs are eligible following a 2-week washout period.
  11. Has received prior radiation therapy within 2 weeks of start of study treatment or has a history of radiation pneumonitis.
  12. Has received radiation therapy to the lung that is >30 Gy within 6 months of the first dose of study treatment.
  13. Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
  14. Any requirement for daily supplemental oxygen.
  15. Any condition requiring systemic treatment with corticosteroids (>10 mg QD prednisone equivalents) or other immunosuppressive medications within 14 days before the first dose of study drug.
  16. Serious or poorly controlled cardiovascular disease.
  17. Chronic hepatitis B or C.
  18. HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
  19. Has an active infection requiring systemic therapy.
  20. Known active or latent tuberculosis.
  21. If the participant had major surgery, must have recovered adequately from the procedure and/or any complications.
  22. Toxicities arising from prior cancer therapy that have not resolved to Grade 1 or baseline.
  23. Red blood cell or platelet infusion within the preceding 2 weeks.
  24. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
  25. Known hypersensitivity to any excipient contained in the drug formulation of KVA121
  26. Any significant history of drug allergy as assessed by the investigator.
  27. Positive urine pregnancy test within 72 hrs of study drug administration.
  28. Participants who are breastfeeding, pregnant, or planning to become pregnant from time of informed consent until at least 120 days after final dose of study drug.
  29. Has a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study.
  30. Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
  31. Inability to comply with study procedures.

View trial on ClinicalTrials.gov


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Phase III Study of Local or Systemic Therapy INtensification DIrected by PET in Prostate CAncer Patients With Post-ProstaTEctomy Biochemical Recurrence (INDICATE)


Condition: Biochemically Recurrent Prostate Carcinoma, Metastatic Prostate Carcinoma, Prostate Adenocarcinoma, Stage IVB Prostate Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04423211

Sponsor: ECOG-ACRIN Cancer Research Group

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • STEP 0: REGISTRATION ELIGIBILITY CRITERIA
  • Patient must be male and >= 18 years of age.
  • Patient must have had a radical prostatectomy (RP) as definitive therapy for histopathologically-proven prostatic adenocarcinoma
  • Patient must have biochemical recurrence (BCR) after RP, defined as follows:
  • If time to BCR, defined as time to first detectable PSA ( > lower limit of normal for assay used) after RP, is < 12 months, a minimum PSA level of >= 0.2 ng/mL and a confirmatory reading of >= 0.2 ng/mL is required, per the American Urological Association (AUA) definition (Note: patients with a persistent PSA reading of at least 0.2 ng/mL are eligible)
  • If time to BCR, defined as time to first detectable PSA (> lower limit of normal for assay used) after RP, is >= 12 months, a minimum absolute PSA of 0.5 ng/mL is required
  • If the patient has a detectable PSA (> lower limit of normal for assay used) at any time after RP AND has an eligible baseline SOC PET (PET1) with at least one positive lesion in any location, then there is no minimum PSA requirement
  • Patients must have no definite evidence for extrapelvic metastatic disease by conventional imaging modalities (CIM) (CT abdomen/pelvis or MRI abdomen/pelvis AND bone scintigraphy, or equivalent), within 26 weeks prior to Step 0 registration. If a patient only has a study-eligible PET/CT or PET/MR (i.e., PET done without prior CIM): if the PET is negative for extrapelvic lesions, then baseline CIM is NOT required. If the PET positive for extrapelvic lesions, then patient should have a baseline CT/MRI for soft tissue lesions and/or a bone scan for osseous lesions
  • Study eligible = PET using FDA-approved radiotracer and performed within 16 weeks prior to study registration
  • Extra-pelvic metastases is defined as any osseous metastases and/or any extrapelvic soft tissue, lymph nodes and organ metastases; extra-pelvic is defined as superior to common iliac bifurcation, outside of standard prostate bed + whole pelvis nodal RT fields. Baseline PET/CT or PET/MR scan (PET1) is eligible for this study if the SOC PET scan is completed with an FDA approved radiotracer for prostate cancer after Step 0 registration and prior to Step 1 randomization OR up to 16 weeks prior to Step 0 registration
  • Patient must be a candidate for SOC post-prostatectomy radiation therapy (RT) to the prostate bed and pelvic nodes with androgen deprivation therapy (ADT)
  • Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Patient must not have started ADT for biochemical recurrence prior to baseline PET (PET1) imaging. A short course of low-dose anti-androgen such as bicalutamide, given after baseline study PET/CT but prior to study registration, is permitted as a brief temporizing measure in advance of starting protocol-approved SOC ADT.
  • Patient must not be enrolled in another therapeutic clinical trial
  • Patient must be able to lie flat and still for approximately 20-30 minutes or otherwise tolerate a PET scan and radiation treatment planning and delivery
  • Patients undergoing a PET/MR must meet local institutional safety guidelines for MRI
  • Patient must not have history of seizures or known condition that may cause predisposal to seizures (e.g., stroke or head trauma resulting in loss of consciousness) within 1 year prior to registration
  • Patient must not have history of inflammatory bowel disease or any gastrointestinal disorder affecting absorption that is expected to increase risk of complication from radiotherapy
  • Hemoglobin (Hgb) >= 9.0 g/dL (independent of transfusion and/or growth factors within 3 months prior to Step 0 registration) (obtained within 8 weeks prior to Step 0 registration)
  • Leukocytes >= 3,000/mcL (obtained within 8 weeks prior to Step 0 registration)
  • Absolute neutrophil count >= 1,500/mcL (obtained within 8 weeks prior to Step 0 registration)
  • Platelets >= 100,000/mcL (obtained within 8 weeks prior to Step 0 registration)
  • Total bilirubin < 1.5 x institutional upper limit of normal (ULN) (patients with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, must have a direct bilirubin of < 1.5 x ULN to be eligible) (obtained within 8 weeks prior to Step 0 registration)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained within 8 weeks prior to Step 0 registration)
  • Creatine < 1.5 x instituional ULN (or measured creatinine clearance > 30 mL/min)
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class I or II (by patient symptoms) or A or B (by objective assessment)
  • Patient must not have completed a course of prior pelvic radiation therapy for any reason
  • Patient must agree not to father children while on study
  • Patient must be English or Spanish speaking to be eligible for the QOL component of the study
  • NOTE: Sites cannot translate the associated QOL forms
  • STEP 1: RANDOMIZATION

Eligibility Criteria:

  • Patient must be male and >= 18 years of age.
  • Patient must have had a radical prostatectomy (RP) as definitive therapy for histopathologically-proven prostatic adenocarcinoma
  • Patient must have biochemical recurrence (BCR) after RP, defined as follows:
  • If time to BCR, defined as time to first detectable PSA ( > lower limit of normal for assay used) after RP, is < 12 months, a minimum PSA level of >= 0.2 ng/mL and a confirmatory reading of >= 0.2 ng/mL is required, per the American Urological Association (AUA) definition (Note: patients with a persistent PSA reading of at least 0.2 ng/mL are eligible)
  • If time to BCR, defined as time to first detectable PSA (> lower limit of normal for assay used) after RP, is >= 12 months, a minimum absolute PSA of 0.5 ng/mL is required
  • If the patient has a detectable PSA (> lower limit of normal for assay used) at any time after RP AND has an eligible baseline SOC PET (PET1) with at least one positive lesion in any location, then there is no minimum PSA requirement
  • Patients must have no definite evidence for extrapelvic metastatic disease by conventional imaging modalities (CIM) (CT abdomen/pelvis or MRI abdomen/pelvis AND bone scintigraphy, or equivalent), within 26 weeks prior to Step 0 registration. If a patient only has a study-eligible PET/CT or PET/MR (i.e., PET done without prior CIM): if the PET is negative for extrapelvic lesions, then baseline CIM is NOT required. If the PET positive for extrapelvic lesions, then patient should have a baseline CT/MRI for soft tissue lesions and/or a bone scan for osseous lesions
  • Study eligible = PET using FDA-approved radiotracer and performed within 16 weeks prior to study registration
  • Extra-pelvic metastases is defined as any osseous metastases and/or any extrapelvic soft tissue, lymph nodes and organ metastases; extra-pelvic is defined as superior to common iliac bifurcation, outside of standard prostate bed + whole pelvis nodal RT fields. Baseline PET/CT or PET/MR scan (PET1) is eligible for this study if the SOC PET scan is completed with an FDA approved radiotracer for prostate cancer after Step 0 registration and prior to Step 1 randomization OR up to 16 weeks prior to Step 0 registration
  • Patient must be a candidate for SOC post-prostatectomy radiation therapy (RT) to the prostate bed and pelvic nodes with androgen deprivation therapy (ADT)
  • Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Patient must not have started ADT for biochemical recurrence prior to baseline PET (PET1) imaging. A short course of low-dose anti-androgen such as bicalutamide, given after baseline study PET/CT but prior to study registration, is permitted as a brief temporizing measure in advance of starting protocol-approved SOC ADT.
  • Patient must not be enrolled in another therapeutic clinical trial
  • Patient must be able to lie flat and still for approximately 20-30 minutes or otherwise tolerate a PET scan and radiation treatment planning and delivery
  • Patients undergoing a PET/MR must meet local institutional safety guidelines for MRI
  • Patient must not have history of seizures or known condition that may cause predisposal to seizures (e.g., stroke or head trauma resulting in loss of consciousness) within 1 year prior to registration
  • Patient must not have history of inflammatory bowel disease or any gastrointestinal disorder affecting absorption that is expected to increase risk of complication from radiotherapy
  • Hemoglobin (Hgb) >= 9.0 g/dL (independent of transfusion and/or growth factors within 3 months prior to Step 0 registration) (obtained within 8 weeks prior to Step 0 registration)
  • Leukocytes >= 3,000/mcL (obtained within 8 weeks prior to Step 0 registration)
  • Absolute neutrophil count >= 1,500/mcL (obtained within 8 weeks prior to Step 0 registration)
  • Platelets >= 100,000/mcL (obtained within 8 weeks prior to Step 0 registration)
  • Total bilirubin < 1.5 x institutional upper limit of normal (ULN) (patients with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, must have a direct bilirubin of < 1.5 x ULN to be eligible) (obtained within 8 weeks prior to Step 0 registration)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained within 8 weeks prior to Step 0 registration)
  • Creatine < 1.5 x instituional ULN (or measured creatinine clearance > 30 mL/min)
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class I or II (by patient symptoms) or A or B (by objective assessment)
  • Patient must not have completed a course of prior pelvic radiation therapy for any reason
  • Patient must agree not to father children while on study
  • Patient must be English or Spanish speaking to be eligible for the QOL component of the study
  • NOTE: Sites cannot translate the associated QOL forms
  • STEP 1: RANDOMIZATION ELIGIBILITY CRITERIA
  • Patient must have completed a baseline SOC PET/CT or PET/MR (PET1 scan) using FDA approved radiotracer with results of extra-pelvic metastases involvement known (positive or negative). The PET1 must have been completed after Step 0 registration and prior to Step 1 randomization OR up to 12 weeks prior to Step 0 registration
  • For patients with negative extra-pelvic metastases, PET-imaging status of intra-pelvic nodes must be known (positive or negative)
  • For patients with positive extra-pelvic metastases (defined as any PET positive lesions outside of standard salvage RT fields [prostate bed +/- typical whole pelvis]), the number of extra-pelvic lesions must be known (1
  • 5 or > 5 extra-pelvic lesions)

View trial on ClinicalTrials.gov


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Randomized Phase II Stereotactic Ablative Radiation Therapy (SABR) for Metastatic Unresected Renal Cell Carcinoma (RCC) Receiving Immunotherapy (SAMURAI)


Condition: Metastatic Renal Cell Carcinoma, Stage III Renal Cell Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Unresectable Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05327686

Sponsor: NRG Oncology

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Pathologically (histologically or cytologically) proven diagnosis of renal cell carcinoma prior to registration
  • Node-positive unresectable (TxN1Mx) or metastatic (TxNxM1) based on the following diagnostic workup:
  • History/physical examination within 45 days prior to registration
  • CT/magnetic resonance imaging (MRI) of the chest/abdomen/pelvis within 45 days prior to registration
  • Patients must have IMDC intermediate (1-2 factors) or poor risk disease (>= 3 factors)
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Patients with measurable disease (node positive or metastatic) as defined by RECIST version 1.1 excluding the primary renal tumor
  • Patient not recommended for or refused immediate cytoreductive nephrectomy
  • Candidate for standard of care therapy with either immuno-oncology (IO)-IO or IO-VEGF combination regimen
  • Primary renal tumor measuring 20 cm or less in anterior to posterior dimension only on axial imaging
  • Age >= 18
  • Karnofsky performance status >= 60 within 45 days prior to registration
  • Hemoglobin >= 8 g/dL (transfusions are allowed) (within 45 days prior to registration)
  • Platelet count >= 50,000/mm^3 (within 45 days prior to registration)
  • Absolute neutrophil count (ANC) >= 1500/mm^3 (within 45 days prior to registration)
  • Calculated (Calc.) creatinine clearance >= 30 mL/min (within 45 days prior to registration)
  • For African American patients specifically whose renal function is not considered adequate by the formula above, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) should be used for calculating the related estimated glomerular filtration rate (GFR) with a correction factor for African American race creatinine clearance for trial eligibility, where GFR >= 30 mL/min/1.73m^2 will be considered adequate
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) (within 45 days prior to registration)
  • Aspartate aminotransferase and alanine aminotransferase (AST and ALT) =< 3 x upper limit of normal (ULN) or < 5 x ULN if hepatic metastases present (within 45 days prior to registration)
  • Patients with known human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Testing is not required for entry into protocol
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load
  • The patient must agree to use a highly effective contraception, including men with vasectomies if they are having sex with a woman of childbearing potential or with a woman who is pregnant, while on study drug and for 6 months following the last dose of study drug. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information

Exclusion Criteria:

  • Patients with planned treatment of all metastatic disease with definitive therapy including either surgery, ablative (non-palliative) doses of radiation, or intervention of some type (definitive interventional radiology techniques) to ALL metastatic sites rendering the patient without extra-renal measurable disease. Patients NOT planned for definitive treatment of all metastatic sites are eligible. Lesions radiated palliatively are not eligible for response assessment
  • Patients with untreated or unstable brain metastases or cranial epidural disease
  • Note: Patients who have been adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator are eligible. Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator
  • Prior radiotherapy to the kidney that would result in overlap of radiation therapy fields treatment of the primary tumor
  • Any systemic therapy for metastatic renal cell carcinoma (RCC) that was initiated > 90 days before registration, note that prior chemotherapy for a different cancer is allowed (completed > 3 years prior to registration)
  • Severe, active comorbidity defined as follows:
  • Active autoimmune disease requiring ongoing therapy including systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications daily. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
  • History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies
  • Active tuberculosis (purified protein derivative [PPD] response without active tuberculosis [TB] is allowed)
  • Uncontrolled hypertension (systolic blood pressure [BP] > 190 mmHg or diastolic BP > 110 mmHg)
  • Major surgery requiring hospital admission ≤ 28 days prior to registration.
  • Any serious (requiring hospital stay or long-term rehab) non-healing wound, ulcer, or bone fracture within 45 days prior to registration
  • Any arterial thrombotic (ST elevation myocardial infarction [STEMI], non-ST elevation myocardial infarction [NSTEMI], cerebrovascular accident [CVA], etc) events within 180 days prior to registration
  • Active New York (NY) Heart Association class 3-4 heart failure symptoms
  • Moderate or severe hepatic impairment (Child-Pugh B or C)
  • Any history of untreated pulmonary embolism or deep venous thrombosis (DVT) within 180 days prior to registration. (Any asymptomatic or treated pulmonary embolism or asymptomatic treated deep venous thrombosis > 30 days prior to registration is allowed)
  • Unstable cardiac arrhythmia within 180 days prior to registration
  • History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 180 days prior to registration
  • History of or active inflammatory bowel disease
  • Malabsorption syndrome within 45 days prior to registration
  • Pregnancy and individuals unwilling to discontinue nursing. For women of child bearing potential must have a negative pregnancy test =< 45 days prior to registration

View trial on ClinicalTrials.gov


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Metastatic castration-sensitive prostate cancer (mCSPC) is a disease state where the benefits of treatment intensification are clear. Androgen receptor pathway inhibitors (ARPIs) offer overall survival benefit when added to conventional androgen deprivation therapy (ADT). The specific ARPIs include abiraterone acetate,1,2 enzalutamide,3,4 and apalutamide.5 Docetaxel chemotherapy offers survival benefit for patients with high volume disease,6 and either abiraterone7 or darolutamide8 offer survival benefit when added to ADT and docetaxel for patients, especially for those with de novo and high-volume mCSPC.
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A Phase 3, Open-label, Randomized, Prospective Study of Apalutamide With Continued Versus Intermittent Androgen-Deprivation Therapy (ADT) Following PSA Response in Participants With Metastatic Castration-Sensitive Prostate Cancer (mCSPC)


Condition: Metastatic Castrate-sensitive Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05884398

Sponsor: Janssen Research & Development, LLC

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • Diagnosis of prostate cancer prior to screening with histologically or cytologically confirmed adenocarcinoma of the prostate
  • Metastatic prostate cancer disease documented by conventional imaging (example, computed tomography [CT], magnetic resonance imaging [MRI], or bone scan) and/or next-generation imaging [NGI] demonstrating greater than equal (>=) 2 distinct extraprostatic sites of metastasis
  • Have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1. Participants with ECOG PS 2 or 3 are eligible for the study if the ECOG PS score is related to stable physical limitations (example, wheelchair-bound due to prior spinal cord injury) and not related to prostate cancer or associated therapy
  • A participant must agree not to plan to conceive a child while enrolled in this study or within 3 months after the last dose of study treatment
  • Must be able to take whole apalutamide tablets by swallowing alone or with another vehicle (example, applesauce)
  • Assigned male at birth, inclusive of all gender identities
  • Participants who have undergone a bilateral orchidectomy and/or who are actively taking gender-affirming hormone therapy as part of their gender affirming care

Exclusion Criteria:

  • History of seizure or known condition that has been determined to significantly predispose to seizure per investigator
  • Pelvic lymph nodes as only site of metastasis
  • Known allergies, hypersensitivity, or intolerance to excipients of apalutamide
  • Any of the following within 6 months prior to screening: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, uncontrolled hypertension, clinically significant arterial or venous thromboembolic events
  • Gastrointestinal disorder affecting absorption

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A Phase 2 Study of Neoadjuvant PARP Inhibition Followed by Radical Prostatectomy in Patients With Unfavorable Intermediate-Risk or High-Risk Prostate Cancer With BRCA1/2 Gene Alterations (NePtune)


Condition: Prostate Cancer, BRCA1 Mutation, BRCA2 Mutation, Prostatic Adenocarcinoma, High-Risk Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05498272

Sponsor: Rana McKay, MD

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Subject must meet all of the following applicable inclusion criteria to participate in this study:
  • Written informed consent and HIPAA authorization for release of personal health information prior to registration.
  • Age ≥ 18 years at the time of consent.
  • T stage 1-3 prostatic adenocarcinoma per AJCC staging manual Ed8.
  • Histologically confirmed adenocarcinoma of the prostate without histological variants comprising >50% of the sample. Patients with intraductal carcinoma are eligible.
  • Must have 3 core biopsies involved with cancer (a minimum of 6 core biopsies must be obtained). Prostate biopsy must be within 7 months from registration. Less than 3 core biopsies are allowed if the patient has >1 cm or T3 disease on magnetic resonance imaging (MRI).
  • Localized unfavorable intermediate or high-risk prostate cancer patients. Patients must have at least one of the following features:
  • Gleason ≥ 4+3 (grade group 3, 4, 5) OR
  • PSA > 20 ng/dL OR
  • T3 disease NOTE: Patients with intraductal carcinoma are eligible independent of Gleason score, PSA and T stage.
  • Must have evidence of germline or somatic BRCA1/2 gene alteration via standard of care CLIA based assay detection. Testing will be confirmed centrally but results of central testing not required for enrollment.
  • No evidence of metastatic disease as determined by radionuclide bone scan and CT/MRI. Lymph nodes must be less than 20 mm in the short (transverse) axis.
  • Participants must be candidates for RP and considered surgically resectable by urologic evaluation.
  • ECOG Performance Status of 0-1 within 28 days prior to registration.
  • Demonstrate adequate organ function as defined below. All screening labs to be obtained within 28 days prior to registration.
  • White blood cell count ≥ 3,000/mcL
  • Absolute neutrophil count ≥ 1,500/mcL
  • Hemoglobin ≥ 10 g/dL with no transfusion support in the past 28 days
  • Platelets ≥ 100,000/mcL
  • Aspartate aminotransferase, alanine aminotransferase, and total bilirubin ≤ 1.5 x Institutional upper limit of normal
  • Calculated creatinine clearance ≥ 51 mL/min based on Cockcroft-Gault formula or 24 hour urine. NOTE: See the protocol for Cockcroft-Gault formula or 24 hour urine.
  • Life expectancy≥ 16 weeks.
  • Subjects must use a condom plus spermicide beginning prior to treatment Cycle 1 Day 1, during treatment and for 3 months after the last dose of olaparib when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential. See protocol for additional details.
  • As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.

Exclusion Criteria:

  • Subjects meeting any of the criteria below may not participate in the study:
  • Active infection requiring systemic therapy.
  • Prior treatments not allowed: hormone therapy for prostate cancer including orchiectomy, antiandrogens (including first-generation antiandrogens, enzalutamide, apalutamide and others), CYP17 inhibitors (including abiraterone, TAK-700, galeterone, ketoconazole, and others), estrogens and radiation therapy. Prior bicalutamide is allowed if taken for < 4 weeks prior to registration and there is a washout period of 2 weeks prior to the initiation of study treatment. LHRH agonist/antagonist therapy is allowed if begun within 4 weeks of registration. Prior 5-alpha reductase inhibitors are allowed but require a washout period of 2 weeks to initiation of study treatment.
  • Prior treatment with a PARP inhibitor.
  • Hypogonadism or severe androgen deficiency as defined by screening serum testosterone < 200 ng/dL.
  • Clinically significant acute infection requiring systemic antibacterial, antifungal, or antiviral therapy including:
  • tuberculosis (clinical evaluation that includes clinical history, physical examination, and radiographic findings, and TB testing in line with local practice).
  • Known active hepatitis infection, positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody at screening. Testing is not required unless there was a prior known positive hepatitis B or C test or hepatitis is suspected at screening. Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • Known to have tested positive for human immunodeficiency virus (HIV) unless currently on effective anti-retroviral therapy with an undetectable viral load within 6 months.
  • Severe hepatic impairment (Child-Pugh Class C).
  • Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
  • Pre-existing condition that warrants long-term corticosteroid use greater than the equivalent of 10 mg prednisone daily. Physiologic replacement is permitted. Topical, intra-articular steroids or inhaled corticosteroids are permitted.
  • Active cardiac disease, defined as:
  • Myocardial infarction within 6 months of study treatment.
  • Uncontrolled angina within 3 months of study treatment.
  • Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, or history of anthracycline or anthracenedione (mitoxantrone) treatment, unless an echocardiogram performed within 3 months of the screening visit results in a left ventricular ejection fraction that is ≥ 45%.
  • History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsade de pointes)
  • Other clinically significant cardiovascular disease within 6 months of registration.
  • Uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation >500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome.
  • Individuals with a history of another malignancy are not eligible if the cancer is under active treatment or the cancer can be seen on radiology scans or if they are off cancer treatment but in the opinion of their oncologist have a high risk of relapse within 5 years.
  • Major surgery within 4 weeks from start of treatment. Subjects must have recovered from any effects as the surgery as assessed by investigator discretion.
  • Treatment with any investigational drug within 28 days prior to registration.
  • Persistent toxicities Grade > 2 caused by previous cancer therapy (per Common Terminology Criteria for Adverse Event (CTCAE)).
  • Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
  • 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, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorders that prohibits obtaining informed consent.
  • Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment.
  • Concomitant use of known strong CYP3A inhibitors. The required washout period prior to starting olaparib is 2 weeks.
  • Concomitant use of known strong or moderate CYP3A inducers. The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
  • Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
  • Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable, for timing refer to the protocol).
  • Patients with a known hypersensitivity to olaparib or any of the excipients of the product.

View trial on ClinicalTrials.gov


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Immunotherapy for prostate cancer is a loaded topic. This is one of the first solid tumors to instill immunotherapy as a standard of care, with sipuleucel-T offering a survival benefit for patients with asymptomatic or minimally symptomatic metastatic castration resistant prostate cancer.1 To rewind even further back, our field of genitourinary oncology has been using immunotherapy, with Bacillus Calmette-Guerin (BCG), for non-invasive muscle invasive bladder cancer. Yet, the rest of the field of oncology has seen dramatic gains with immunotherapy, especially in the form of checkpoint inhibitors; its use has become common practice for most cancers. Unfortunately, prostate cancer has not seen major immunotherapy advances, with accumulation of many negative randomized phase 3 trial attempts, spanning vaccines, like Prostvac,2 and checkpoint inhibitors, like anti-PD-(L)13,4 or anti-CTLA-45,6 antibodies.
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A Phase I/II Study of M9241 With Docetaxel and Abiraterone in Adults With Metastatic Castration Sensitive and M9241 With Docetaxel in Castration Resistant Prostate Cancer


Condition: Cancer Of Prostate, Prostate Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04633252

Sponsor: National Cancer Institute (NCI)

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • Participants must have documented histopathological confirmation of prostate cancer. If no pathologic specimen is available, participants may enroll with a pathologist's report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.
  • Participants must have metastatic disease, defined as at least one lesion on TC99 bone scan or at least one lesion that is measurable per, per RECIST 1.1.
  • mCSPC participants:
  • Participants must be within 134 days of starting ADT.
  • If participants are on ADT and responding, this may impact the findings on scans. Pre- treatment scans could be used to confirm that participants have metastatic high-volume disease in such cases.
  • For Cohorts 1 and 2, Dose escalation and Safety Run-in, only: mCSPC may have high or low volume disease.
  • For Cohort 3, Dose Expansion: mCSPC participants must have high volume disease (as defined by visceral lesion or 4 or greater bone lesions, at least one of which is beyond the spine and pelvis).
  • mCRPC participants:
  • Must need ADT as part of their cancer therapy (unless previous orchiectomy)
  • Must have been previously treated with modern anti-androgens such as abiraterone, enzalutamide, apalutamide, or darolutamide.
  • Must have not had progression while on docetaxel if given for mCSPC or within 3 months of completing docetaxel for mCSPC.
  • Progression defined as either rising PSA greater than 2.0 ng/ml or radiographic evidence of progression seen on CT scan or TC-99 bone scan.
  • Toxicities related to prior therapy, including surgery and/ or radiation, must have resolved to <= grade 1.
  • Men age >=18 years. Because no dosing or adverse event data are currently available on the use of M9241 in combination with docetaxel in participants <18 years of age, children are excluded from this study.
  • ECOG performance status 0-2.
  • Participants must have adequate organ and marrow function as defined below:
  • Absolute neutrophil count >=1,500/mcL, without CSF support
  • Platelets >=100,000/mcL
  • Hemoglobin >9 g/dL
  • PT <= 1.5 x ULN
  • aPTT <= 1.5 x ULN
  • Total bilirubin <= upper limit of normal (ULN), OR in participants with Gilbert s syndrome, a total bilirubin <= 3.0
  • Serum albumin >=2.8 g/dL
  • AST(SGOT)/ALT(SGPT) <=1.5 X institutional upper limit of normal -- Hepatic function based on Child-Pugh Class: Participants with hepatic impairment must have Child-Pugh Class A or better
  • Serum Creatinine OR Creatinine Clearance <= 1.5 X institutional upper limits of normal OR >=50 mL/min/1.73 m^2 calculated by eGFR in the clinical lab for participants with serum creatinine levels > 1.5 ULN
  • The effects of M9241 in combination with docetaxel and abiraterone on the developing human fetus are unknown. For this reason and because docetaxel agents as well as other immuno-therapeutic agents used in this trial are known to be teratogenic, sexually active subjects and their female partners must agree to use medically accepted barrier methods of contraception (e.g., male or female condom)after enrollment on study , during the study treatment and for 4 months after the last dose of abiraterone, docetaxel or M921, even if oral contraceptives are also used. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately and her partner should inform the study doctor immediately.
  • Ability of subject to understand and the willingness to sign a written informed consent document. Subject should be willing to travel to the NIH for follow-up visits.
  • Participants with prior immune checkpoint therapy are eligible to enroll upon PI discretion.

Exclusion Criteria:

  • Immunocompromised status due to:
  • Human immunodeficiency virus (HIV) positivity
  • Active autoimmune diseases such as Addison's disease, Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Grave's disease. Participants with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including CNS, heart, lungs, kidneys, skin, and GI tract will be allowed.
  • Other immunodeficiency diseases that in the opinion of the investigator could compromise the participants or limit treatment efficacy
  • Serious intercurrent medical illness that, in the judgment of the investigator, would interfere with a participant s ability to carry out the treatment program.
  • Current use of other medications for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (e.g. phytoestrogens and saw palmetto).
  • Concurrent use of CYP3A4 inducers or sensitive CYP2D6 substrates within 14 days or 5 half-lives, whichever is shorter.
  • Receipt of any investigational agent within 28 days (or 60 days for an antibody drug conjugates) before the first planned dose of study drugs.
  • Participants who are positive for Hepatitis B surface antigen and/or Anti-Hepatitis C antibody
  • Uncontrolled hypertension (SBP>170/ DBP>105)
  • Has received or will receive a live vaccine within 30 days prior to the first administration of study intervention. Seasonal flu vaccines that do not contain a live virus are permitted. Locally approved COVID vaccines are permitted.
  • Participants who have had prior docetaxel for mCRPC
  • mCSPC participants will be excluded if they did not start abiraterone within 6 weeks of ADT and/or had any docetaxel
  • Participants who have had progression within 3 months of completing docetaxel for mCSPC
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to M9241 investigational agents used in the study
  • The subject has had evidence within 3 years of the start of study treatment of another active malignancy which required systemic treatment (except for nonmelanoma skin cancers or carcinoma in situ of the bladder).
  • The subject has active brain metastases or epidural disease.
  • Participants with greater than or equal to grade 2 peripheral neuropathy (defined by CTCAE 5.0) at baseline.

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Multiple-Arm Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of XmAb20717 in Combination With Standard of Care Treatment in Patients With Metastatic Castration Sensitive Prostate Cancer


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

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05733351

Sponsor: Emory University

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  • Age >= 18 years
  • Histologically confirmed adenocarcinoma of the prostate with metastatic disease
  • Castration-sensitive status: either not have been treated with androgen deprivation therapy (ADT) (hormone therapy) or not on ADT at the time of progression
  • Participants can have received up to 3 months of ADT with luteinizing hormone-releasing hormone (LHRH) agonists or antagonists or orchiectomy with or without concurrent first-generation antiandrogens prior to enrollment, with no radiographic evidence of disease progression or rising prostate-specific antigen (PSA) prior to enrollment
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy > 12 weeks as determined by the investigator
  • Hemoglobin >= 9.0 g/dl (within 28 days of cycle 1 day 1) (no transfusions allowed within 7 days of Cycle 1 Day 1 to meet entry criteria)
  • White blood cell (WBC) >= 2000/uL (within 28 days of cycle 1 day 1) (after at least 7 days without growth factor support or transfusion)
  • Absolute neutrophil count (ANC) >= 1,500/mcL (within 28 days of cycle 1 day 1) (after at least 7 days without growth factor support or transfusion)
  • Platelets >= 100,000/mcL (within 28 days of cycle 1 day 1) (no transfusions allowed within 7 days of cycle 1 day 1 to meet entry criteria)
  • Prothrombin time (PT)/ partial thromboplastin time (PTT) =< 1.5 x upper limit of normal (ULN) (within 28 days of cycle 1 day 1)
  • Total bilirubin =< 1.5 institutional upper limit of normal (ULN) (within 28 days of cycle 1 day 1)
  • Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =< 3 institutional upper limit of normal (ULN) (within 28 days of cycle 1 day 1)
  • Serum creatinine =< 2 mg/dL (or glomerular filtration rate >= 40 mL/min) (within 28 days of cycle 1 day 1)
  • Willingness to provide pre- and post-treatment fresh tumor biopsies, if safe and medically feasible
  • Male subjects must be surgically sterile or must agree to use adequate method of contraception from the time of consent until at least 120 days after the last dose of Xmab27017
  • Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol specified laboratory tests, other study procedures, and study restrictions
  • Completion of all previous surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy for the treatment of cancer >= 2 weeks before the start of study therapy. (No radiotherapy to Xmab27017 injection site within 4 weeks)
  • Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier (i.e., have residual toxicities > grade 1)
  • Patients who are receiving any other investigational agents or an investigational device within 21 days before administration of first dose of study drugs
  • Prior treatment with any CTLA4, PD1, or PDL1, or directed immunotherapy
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to (investigational new drug [IND] agent[s]) or other agents used in study
  • Have known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable, ie, are without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), are clinically stable, and are without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
  • Active known or suspected autoimmune disease (except that subjects are permitted to enroll if they have vitiligo; type 1 diabetes mellitus or residual hypothyroidism due to an autoimmune condition that is treatable with hormone replacement therapy only; psoriasis, atopic dermatitis, or another autoimmune skin condition that is managed without systemic therapy; or arthritis that is managed without systemic therapy beyond oral acetaminophen and nonsteroidal anti-inflammatory drugs)
  • Has any condition requiring systemic treatment with corticosteroids, prednisone equivalents, or other immunosuppressive medications within 14 days prior to first dose of study drug (except that inhaled or topical corticosteroids or brief courses of corticosteroids given for prophylaxis of contrast dye allergic response are permitted.)
  • 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
  • Receipt of an organ allograft
  • Known history of left ventricular ejection fraction =< 40%
  • Receipt of a live-virus vaccine within 30 days prior to first dose of study drug (seasonal flu vaccines that do not contain live virus are permitted. COVID-19 vaccines are permitted)
  • Known human immunodeficiency virus (HIV) positive subject with CD4+ T-cell (CD4+) counts < 350 cells/uL, or an HIV viral load greater than 400 copies/mL, or a history of an AIDS (acquired immunodeficiency syndrome)-defining opportunistic infection within the past 12 months, or who has not been on established antiretroviral therapy (ART) for at least 4 weeks prior to initiation of study drug dosing. (Effective ART is defined as a drug, dosage, and schedule associated with reduction and control of the viral load.)
  • Known positive test for hepatitis C ribonucleic acid (RNA) (a subject who is hepatitis C virus [HCV] antibody positive but HCV RNA negative due to documented, curative prior antiviral treatment or natural resolution is eligible).
  • Known positive test for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb; a subject whose HBsAg is negative and HBcAb is positive may be enrolled if a hepatitis B virus [HBV] deoxyribonucleic acid (DNA) test is negative, and the subject is retested for HBsAg and HBV DNA every 2 months)

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Phase I/II Trial of Pembrolizumab and Androgen-receptor Pathway Inhibitor With or Without 225Ac-J591 for Progressive Metastatic Castration Resistant Prostate Cancer


Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04946370

Sponsor: Weill Medical College of Cornell University

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • Male participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of prostate adenocarcinoma.
  • A male participant must agree to use a contraception during the treatment period and for at least 4 months after the last dose of study treatment and refrain from donating sperm during this period.
  • Documented progressive metastatic CRPC based on Prostate Cancer Working Group 3 (PCWG3) criteria, which includes at least one of the following criteria: PSA progression, Objective radiographic progression in soft tissue, New bone lesions
  • ECOG performance status of 0-1
  • Have serum testosterone < 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone orchiectomy.
  • Have previously been treated with at least one of the following in any disease state: Androgen receptor signaling inhibitor (such as enzalutamide), CYP 17 inhibitor (such as abiraterone acetate). These drugs may have been initiated in the metastatic hormone sensitive or non-metastatic (M0) CRPC setting provided they meet criteria for progressive mCRPC at study entry.
  • Age > 18 years
  • Patients must have normal organ and marrow function as defined: Absolute neutrophil count >2,000 cells/mm3, Hemoglobin ≥9 g/dL, Platelet count >150 x 10^3/mcL, Serum creatinine <1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 mL/min/1.73 m2 by Cockcroft-Gault, Serum total bilirubin <1.5 x ULN (unless due to Gilbert's syndrome in which case direct bilirubin must be normal), Serum AST and ALT <3 x ULN in absence of liver metastases; < 5x ULN if due to liver metastases (in both circumstances bilirubin must meet entry criteria), Serum internalized normalized ratio (INR) OR prothrombin time (PT) AND activated partial thromboplastin time (aPTT) must be <1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Prior receipt of chemotherapy for castration-resistant prostate cancer. Prior receipt of docetaxel chemotherapy in the hormone sensitive setting or for localized disease is acceptable provided at least 6 months has passed since the last dose.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
  • Prior bone-seeking beta-emitting radioisotopes (e.g. Sm-153, Sr-89) or investigational PSMA-targeted therapy; prior radium-223 is allowed provided last dose administered >12 weeks prior to C1D1 on this study
  • Has a history of a second malignancy, unless treatment with curative intent has been completed with no evidence of malignancy for 2 years. Patients with treated localized non-melanoma skin care, non-muscle invasive urothelial carcinoma, or carcinoma in-situ of other site are not excluded.
  • Known history of myelodysplastic syndrome
  • Has a known history of Human Immunodeficiency Virus (HIV) infection
  • Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
  • Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks or <5 half-lives prior to enrollment.
  • Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
  • Diagnosis of deep vein thrombosis and/or pulmonary embolus within 1 month of C1D1
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Has received radiotherapy within 4 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
  • Patients on stable dose of bisphosphonates or denosumab, which have been started no less than 4 weeks prior to treatment start, may continue on this medication, however patients are not allowed to initiate bisphosphonate/Denosumab therapy during the DLT-assessment period of the study. These drugs may be added after week 12.
  • Unless azoospermia is present (whether due to surgery or underlying medical condition), having partners of childbearing potential and not willing to use a method of birth control deemed acceptable by the principal investigator and chairperson during the study and for 4 months after last study drug administration.
  • Is expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment
  • Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines are allowed.
  • Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
  • Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Has an active infection requiring systemic therapy at the time of treatment initiation
  • Has a known history of active TB (Bacillus Tuberculosis)
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Has had an allogenic tissue/solid organ transplant

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Cabazitaxel in Combination With 177Lu-PSMA-617 in Metastatic Castration-resistant Prostate Cancer


Condition: Metastatic Castration-resistant Prostate Cancer, mCRPC

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05340374

Sponsor: Peter MacCallum Cancer Centre, Australia

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  1. Male patients aged 18 years or older at the time of informed consent.
  2. Patient has provided written informed consent.
  3. Histologically confirmed adenocarcinoma of the prostate without neuroendocrine or small cell differentiation.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
  5. Patients must have had prior treatment with docetaxel.
  6. Patients must have progressed on a second-generation androgen receptor (AR)-targeted agent (e.g., enzalutamide, abiraterone, or apalutamide) in the castrate-resistant setting.
  7. Patients must have progressive disease. The Prostate Cancer Clinical Trials Working Group 3 (PCWG3) defines this as any one of the following:
  8. PSA progression: minimum of two rising PSA values from a baseline measurement with an interval of ≥ 1 week between each measurement
  9. Soft tissue or visceral disease progression as per Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) criteria
  10. Bone progression: ≥ 2 new lesions on bone scan
  11. At least three weeks since the completion of surgery prior to registration.
  12. Prior surgical orchiectomy or chemical castration maintained on luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist).
  13. Serum testosterone levels ≤ 1.75nmol/L within 28 days prior to registration.
  14. Imaging evidence of metastatic disease documented with either whole body bone scan (WBBS) or computed tomography (CT) scan performed within 28 days prior to registration.
  15. Significant prostate-specific membrane antigen (PSMA) avidity on PSMA PET/CT, defined as a minimum uptake of SUVmax 15 at a site of disease.
  16. Patients must have a life expectancy ≥ 12 weeks.
  17. Assessed by a medical oncologist as suitable for treatment with cabazitaxel and 177Lu-PSMA-6
  18. Patients must have adequate bone marrow, hepatic and renal function documented within 28 days prior to registration, defined as:
  19. Haemoglobin ≥ 90 g/L independent of transfusions (no red blood cell transfusion in last 28 days prior to registration)
  20. Absolute neutrophil count (ANC) ≥ 1.5x10^9/L
  21. Platelets ≥ 150 x10^9/L
  22. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) except for patients with known Gilbert's syndrome, where this applies for the unconjugated bilirubin component
  23. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN if there is no evidence of liver metastasis or ≤ 5 x ULN in the presence of liver metastases
  24. Albumin ≥ 25 g/L
  25. Adequate renal function: patients must have a creatinine clearance estimated of ≥ 40 mL/min using the Cockcroft-Gault equation
  26. Sexually active patients are willing to use medically acceptable forms of barrier contraception.
  27. Willing and able to comply with all study requirements, including all treatments and the timing and nature of all required assessments.

Exclusion Criteria:

  1. Superscan on WBBS or diffuse marrow disease on PSMA PET.
  2. Site(s) of measurable disease that are FDG-positive with low PSMA expression (SUVmax <10).
  3. Prior treatment with cabazitaxel or 177Lu-PSMA-6
  4. Contraindications to the use of corticosteroid treatment.
  5. Other malignancies within the previous 2-years other than basal cell or squamous cell carcinomas of skin or other cancers that are unlikely to recur within 24 months.
  6. Presence of untreated brain metastases or leptomeningeal metastases.
  7. Patients with symptomatic or impending cord compression unless appropriately treated beforehand and clinically stable for ≥ four weeks.
  8. Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety.
  9. Persistent toxicities (CTCAE v5.0 >/= Grade 2) caused by previous cancer therapy, excluding alopecia.
  10. Known HIV or hepatitis B or C infection.
  11. Radiotherapy or systemic anti-cancer therapies administered within 14 days prior to registration, excluding androgen deprivation therapy (ADT).

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Combination of Radium-223 and Lutetium-177 PSMA-I&T in Men With Metastatic Castration-Resistant Prostate Cancer


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

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05383079

Sponsor: Peter MacCallum Cancer Centre, Australia

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • Patient must be ≥ 18 years of age and must have provided written informed consent.
  • Histologically or cytologically confirmed adenocarcinoma of the prostate, OR unequivocal diagnosis of metastatic prostate cancer. (i.e. involving bone or pelvic lymph nodes or para-aortic lymph nodes) with an elevated serum PSA.
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
  • Patients must have progressed on ≥ 1 second-generation AR-targeted agent (e.g., enzalutamide, abiraterone, apalutamide, or darolutamide).
  • Patients must have progressive disease for study entry. PCWG3 defines this as any one of the following:
  • PSA progression: minimum of two rising PSA values from a baseline measurement with an interval of ≥ 1 week between each measurement.
  • Soft tissue progression as per RECIST 1.1 criteria
  • Bone progression: ≥ 2 new lesions on bone scan
  • Symptomatic progression eg. Bone pain
  • At least three weeks since receiving anti-cancer treatment (other than ADT), the completion of surgery or radiotherapy prior to registration.
  • Prior surgical orchiectomy or chemical castration maintained on luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist).
  • Serum testosterone levels ≤ 1.75nmol/L (≤ 50ng/dL) within 28 days before registration.
  • Significant PSMA avidity on PSMA PET/CT, defined as a minimum uptake of SUVmax 20 at a site of disease, and SUVmax >10 at sites of measurable disease >10mm (unless subject to factors explaining a lower uptake, e.g. respiratory motion, reconstruction artefact).
  • ≥ 2 bone metastases must be present on bone scintigraphy which have not been previously treated with radiotherapy.
  • No contraindication to treatment with a bone antiresorptive agent such as denosumab or zoledronic acid.
  • Patients must have adequate bone marrow, hepatic and renal function documented within 28 days prior to registration, defined as:
  • Haemoglobin ≥ 90 g/L independent of transfusions (no red blood cell transfusion in last four weeks)
  • Absolute neutrophil count ≥ 1.5x10^9/L
  • Platelets ≥ 150 x10^9/L
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) except for patients with known Gilbert's syndrome, where this applies for the unconjugated bilirubin component.
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN if there is no evidence of liver metastasis or ≤ 5 x ULN in the presence of liver metastases
  • Albumin ≥ 25 g/L
  • Adequate renal function: patients must have a creatinine clearance estimated of ≥ 40 mL/min using the Cockcroft Gault equation
  • Sexually active patients are willing to use medically acceptable forms of barrier contraception.
  • Willing to undergo biopsies, if disease is considered accessible and biopsy is feasible.
  • Willing and able to comply with all study requirements, including all treatments and the timing and nature of all required assessments.

Exclusion Criteria:

  • Patients who meet any of the following criteria will be excluded from study entry:
  • Superscan on Bone scan (WBBS) or diffuse marrow involvement on PSMA PET/CT
  • Prior treatment with 223Ra or 177Lu-PSMA.
  • Has received more than one previous line of chemotherapy for the treatment of metastatic prostate cancer.
  • Sites of discordant FDG-positive disease defined by minimal PSMA-expression and no uptake on WBBS (for bone metastases).
  • Other malignancies within the previous 2 years other than basal cell or squamous cell carcinomas of skin or other cancers that are unlikely to recur within 24 months.
  • Symptomatic brain metastases or leptomeningeal metastases.
  • Patients with symptomatic or impending cord compression unless appropriately treated beforehand and clinically stable for ≥ four weeks.
  • Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety.

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A Phase 3, Randomized Study of Adjuvant Cretostimogene Grenadenorepvec Versus Observation for the Treatment of Intermediate Risk Non-Muscle Invasive Bladder Cancer (IR-NMIBC) Following Transurethral Resection of Bladder Tumor (TURBT)


Condition: Non Muscle Invasive Bladder Cancer, Urologic Cancer, Bladder Cancer, Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06111235

Sponsor: CG Oncology, Inc.

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • Pathologically confirmed IR-NMIBC, per American Urologic Association/Society of Urologic Oncology/National Comprehensive Cancer Network guidelines, within 12 weeks of participant randomization: 1. Recurrent LG Ta within 12 months of prior LG or HG (HG Ta ≤ 3 cm) tumor 2. Solitary LG Ta >3 cm tumor 3. Multifocal LG Ta tumors 4. Primary and solitary HG Ta ≤3 cm tumor 5. LG T1 tumor
  • All visible disease removed by TURBT within 12 weeks of study randomization
  • Acceptable baseline organ function

Exclusion Criteria:

  • High-risk NMIBC (e.g., HG T1, Recurrent or multifocal HG Ta>3cm tumor(s), CIS)
  • Low-Risk NMIBC (e.g., solitary LG Ta ≤3 cm tumor)
  • Disease in the prostatic urethra at any time or in the upper genitourinary tract within 24 months of randomization
  • Muscle-invasive bladder cancer, locally advanced or metastatic bladder cancer
  • Prior treatment with any human adenovirus serotype 5 based therapy (e.g., Ad-interferon or Adstiladrin)

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Metastatic castration-sensitive prostate cancer (mCSPC) is a disease state that has grown in complexity, with arguably some of the greatest gains in our field of genitourinary oncology. That’s because the benefits of treatment intensification are indisputable with outstanding clinical trial hazard ratios and large median overall survival benefits. To briefly summarize, androgen receptor pathway inhibitors (ARPI) offer overall survival benefits when added to conventional androgen deprivation therapy (ADT). These benefits extend to abiraterone acetate,1,2 enzalutamide,3,4 and apalutamide.5 Docetaxel chemotherapy offers survival benefit for patients with high volume disease,6 and either abiraterone7 or darolutamide8 offer survival benefits when added to ADT and docetaxel for patients with de novo and high-volume mCSPC. There is also supportive data for low volume prostate cancer to apply prostate directed radiation for survival benefit from a subgroup analysis of the STAMPEDE trial.9
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A Phase 1, Open-label, Dose-escalation Study to Investigate the Safety, Tolerability, and Pharmacokinetics of UGN-301 (Zalifrelimab) Administered Intravesically as Monotherapy and in Combination With Other Agents in Patients With Recurrent NMIBC


Condition: Non-muscle Invasive Bladder Cancer, NMIBC, Carcinoma in Situ of Bladder, Bladder Cancer, Urothelial Carcinoma Bladder, Urothelial Carcinoma Recurrent

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05375903

Sponsor: UroGen Pharma Ltd.

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  • 1. Able to give informed consent. 2. Arm A: Have confirmed recurrent NMIBC with HG Ta and/or T1 disease and/or CIS or recurrent IR LG Ta and/or T1 disease. Arm B: Have confirmed recurrent NMIBC with HG Ta and/or T1 disease and/or CIS. Arm C: Have confirmed recurrent NMIBC with HG Ta and/or T1 disease and/or CIS. 3. Patients with HG Ta and/or T1 disease and/or CIS must meet one of the following criteria: • Have Bacillus Calmette-Guérin (BCG)-unresponsive disease, defined as 1) persistent or recurrent CIS alone or with recurrent Ta/T1 disease within 12 months of completion of adequate BCG therapy, or 2) recurrent HG Ta/T1 disease within 6 months of completion of adequate BCG therapy, or 3) HG T1 disease at the first evaluation following a BCG induction course. Notes: Adequate BCG therapy is defined as at least 5 of 6 doses of an initial induction course plus 1) at least 2 of 3 doses of maintenance therapy or 2) at least 2 of 6 doses of a second induction course. Patients with BCG-unresponsive disease also must be unwilling or unfit to undergo radical cystectomy.
  • Have otherwise failed adequate BCG therapy (eg, recurrence > 6 months [papillary] or > 12 months [CIS] after last BCG exposure).
  • Are BCG intolerant, defined as the inability to tolerate at least one full induction course of BCG.
  • Have HG Ta disease with tumors ≤ 3 cm and failed at least one previous course of therapy (eg, adjuvant intravesical chemotherapy). 4. Have all papillary tumors visible by white light resected, and obvious areas of CIS fulgurated during Screening or within 6 weeks before Screening. Note: Blue light cystoscopy is not permitted. 5. Eastern Cooperative Oncology Group (ECOG) status ≤ 2. 6. Absence of concomitant upper tract urothelial carcinoma (UTUC) or urothelial carcinoma (UC) within the prostatic urethra. Freedom from upper tract disease (if clinically indicated) as indicated by no evidence of upper tract tumor by either intravenous pyelogram, retrograde pyelogram, computerized tomography (CT) urogram with or without contrast, or magnetic resonance imaging (MRI) urogram with or without contrast performed within 6 months of enrollment. 7. Patients with prostate cancer on active surveillance at very low, low, or intermediate risk for progression, defined as Gleason Grade Group 1 or 2, Gleason score ≤ 7, with prostate-specific antigen < 20 ng/dL, and cT1-cT2b (NCCN, 2023) are permitted to be in the study at the discretion of the investigator (see exclusion criterion 8). 8. Female patients of childbearing potential must use maximally effective birth control during the period of therapy, must be willing to use contraception for 1 month following the last administration of study drug and must have a negative urine or serum pregnancy test upon entry into this study. Otherwise, female patients must be postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile. "Maximally effective birth control" means that the patient, if sexually active, should be using a combination of 2 methods of birth control that are approved and recognized to be effective by health authorities. 9. Male patients must be surgically sterile or willing to use 2 highly effective forms of birth control upon enrollment, during the course of the study, and for 1 month following the last study drug instillation. 10. Has adequate organ and bone marrow function within 14 days of treatment initiation as determined by routine laboratory tests outlined below:
  • Leukocytes ≥ 3,000/μL;
  • Absolute neutrophil count (ANC) ≥ 1,500/μL;
  • Platelets ≥ 100,000/μL;
  • Hemoglobin ≥ 9.0 g/dL;
  • Total bilirubin ≤ 1.5 × upper limit of normal (ULN);
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 × ULN;
  • Alkaline phosphatase (ALP) ≤ 2.5 × ULN;
  • Estimated creatinine clearance ≥ 30 mL/min calculated using the Cockcroft-Gault equation. 11. Has a life expectancy > 12 months.

Exclusion Criteria:

  1. Current or previous evidence of muscle invasive, locally advanced nonresectable, or metastatic urothelial carcinoma (ie, T2, T3, T4 and/or stage IV).
  2. Current systemic therapy for bladder cancer.
  3. Prior therapy with an anti-cytotoxic T lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1), anti-PD-ligand 1 (L1) agent, or with an agent directed to another co-inhibitory T-cell receptor.
  4. Active infection requiring systemic therapy including urinary tract infection (once satisfactorily treated, patients can enter the study).
  5. Active systemic autoimmune disease that required systemic treatment in the past 2 years. Short courses of steroids (≤ 14 days) for medical reasons without anticancer intent (eg, atopic dermatitis, psoriasis, infection, allergic reaction) are permitted if the last dose was ≥ 4 weeks before the first dose of study treatment.
  6. Women who are pregnant or nursing.
  7. Any medical psychological, familial, sociological, or geographical condition that, in the opinion of the Investigator, would preclude participation in the study.
  8. History of malignancy of other organ system within the past 5 years, except previously treated UTUC, basal cell carcinoma or squamous cell carcinoma of the skin, and/or prostate cancer under active surveillance (see inclusion criterion 8).
  9. Patients who cannot tolerate intravesical dosing or intravesical surgical manipulation.
  10. Intravesical therapy within 4 weeks before starting study treatment.
  11. Has participated in a study of an investigational agent and received study therapy or received investigational device within 4 weeks before the first dose of study treatment.
  12. Has received an immune modulator therapy within 5 half-lives of starting study treatment.
  13. Has received a vaccine within 2 weeks before starting study treatment.
  14. Has a known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.

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A 2-stage, Lead-in and Randomized, Phase 2, Open-label Study of Darolutamide Versus Enzalutamide as Monotherapy on Testosterone Levels Change in Men With Hormone-Naïve Prostate Cancer


Condition: Biochemically Recurrent Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05526248

Sponsor: Bayer

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Male of ≥ 18 years of age.
  • Patients must have histologically or cytologically confirmed adenocarcinoma of the prostate.
  • Prior treatment with primary radical prostatectomy or definitive RT for localized prostate cancer
  • Patients must have PSA ≥0.2 ng/mL after ART or SRT post-RP or after RP in participants who are unfit for ART or SRT, OR PSA ≥2 ng/mL above the nadir after primary RT only. (RP, radical prostatectomy; ART, adjuvant radiotherapy; SRT, salvage radiotherapy; RT primary radiotherapy)
  • The presence of < 5 asymptomatic metastatic lesions on conventional or PSMA-PET based imaging methods permitted. Lesions that need treatment with any opioid based analgetic are considered symptomatic
  • PSADT ≤ 20 months calculated per PCWG3 + RECIST 1.1 per Scher et al. (Scher et al. 2016) and MSKCC nomogram.
  • Eastern Cooperative Oncology Group ECOG (PS) of 0
  • 1.
  • Serum testosterone >150 ng/dl.
  • Patients must have adequate organ function within 4 weeks before the first dose of study intervention.
  • More than 30 days (or 5 half-lives) (whichever is longer) since prior participation in another clinical trial with an investigational medicinal product.

Exclusion Criteria:

  • Prior treatment with ADT of up to 6 months for localized disease is permitted but not if during the prior 6 months before first dose of study intervention. Plan to initiate ADT during the trial period is not allowed.
  • Radiation therapy or major surgery within 4 weeks of screening.
  • Systemic glucocorticoids within 3 months prior to the first dose or study intervention was expected to require systemic glucocorticoids during the study period
  • Had any of the following within 6 months before randomization: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, congestive heart failure (New York Heart Association Class III or IV)
  • Uncontrolled hypertension
  • A gastrointestinal disorder or procedure which is expected to interfere significantly with absorption of study intervention.
  • Prior history of a clinically significant malignancy with the exception of basal cell, squamous cell carcinoma of the skin, and superficial bladder cancer.
  • Prior treatment with:
  • Second-generation androgen receptor (AR) inhibitors such as enzalutamide, apalutamide, darolutamide other investigational AR inhibitors
  • or Cytochrome P17 enzyme inhibitor such as abiraterone acetate as antineoplastic treatment for prostate cancer
  • Prior history of gynecomastia
  • Use of herbal products that may have had hormonal anti-prostate cancer activity or were known to decrease PSA levels (e.g., saw palmetto) within 4 weeks before the first dose of study intervention

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A Phase 1/2 Study of EPI-7386 in Combination With Enzalutamide Compared With Enzalutamide Alone in Subjects With Metastatic Castration-Resistant Prostate Cancer


Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05075577

Sponsor: ESSA Pharmaceuticals

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • Males ≥18 years.
  • Histologically, pathologically, or cytologically confirmed prostate adenocarcinoma.
  • Evidence of castration-resistant prostate cancer (CRPC).
  • Presence of metastatic disease at study entry documented by 1 or more bone lesions on bone scan or by soft tissue disease observed by CT/MRI.
  • Naïve to second generation anti-androgens.
  • Evidence of progressive disease defined as 1 or more Prostate Cancer Working Group 3 (PCWG3) criteria.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Ongoing ADT with luteinizing hormone-releasing hormone (LHRH) agonist/antagonist therapy or history of bilateral orchiectomy, with castrate level testosterone.
  • Serum testosterone ≤1.73 nmol/L (50 ng/dL).
  • Subjects receiving bisphosphonates or other approved bone-targeting therapy (e.g., denosumab) must be on a stable dose for at least 28 days prior to the start of study treatment.
  • Demonstrate adequate organ function.

Exclusion Criteria:

  • Biologic anti-cancer therapy within 28 days prior to the start of study treatment.
  • Use of hormonal agents with anti-tumor activity against prostate cancer within 28 days prior to the start of study treatment.
  • Use of herbal products or alternative therapies that may decrease PSA levels or that may have hormonal anti-prostate cancer activity within 28 days prior to the start of study treatment or plans to initiate during the study.
  • Intervention with any chemotherapy, investigational agents, or other anti-cancer drugs within 28 days of the first dose of study treatment.
  • Use of radium-223 dichloride or other radioligand/radiopharmaceutical within 28 days prior to the start of study treatment.
  • Received limited-field palliative bone radiotherapy >5 fractions and/or any radiotherapy within 2 weeks prior to the start of study treatment.
  • Received a blood transfusion within 28 days of hematologic screening labs.
  • Known intra-cerebral disease or brain metastasis unless adequately treated and stable for the last 28 days before signing of informed consent.
  • Spinal cord compression.
  • Diagnosis of another clinically significant malignancy within the previous 3 years other than curatively treated non-melanomatous skin cancer or superficial urothelial carcinoma and other in situ or non-invasive malignancies.
  • Gastrointestinal issues affecting absorption.
  • Significant cardiovascular disease.
  • Known history of seizure or conditions that may pre-dispose them to seizure, including brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, and brain arteriovenous malformation.
  • Concurrent disease or any clinically significant abnormality.
  • Known or suspected hypersensitivity to any components of the formulation used for EPI-7386 or enzalutamide.
  • Use of strong inhibitors of CYP2C8.
  • Use of strong inducers of CYP3A.
  • Use of narrow therapeutic index sensitive CYP2C8 or sensitive substrates for CYP3A and CYP2B6.
  • Use of granulocyte colony stimulating factor within 7 days prior to screening laboratories.
  • Not a candidate for enzalutamide treatment.
  • Patients with rare hereditary problems of fructose intolerance.

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