Brief Summary
This study is a first-in-human, Phase 1, open-label, multicenter study to assess the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and the preliminary efficacy of JANX007 in adults with metastatic castration-resistant prostate cancer (mCRPC).
Protocol Interventions
Biological: JANX007, Drug: Darolutamide
Brief Summary
This study is a substudy being conducted under one pembrolizumab umbrella master study KEYMAKER-U04. The substudy will consist of 2 parts. Part 1 will evaluate the safety and preliminary efficacy of sacituzumab tirumotecan plus enfortumab vedotin (EV). Part 2 will be based on Part 1 results and will evaluate the efficacy, pharmacokinetics, and safety of sacituzumab tirumotecan plus EV in combination with pembrolizumab in participants with advanced urothelial carcinoma.
Protocol Interventions
Biological: Sacituzumab tirumotecan, Biological: Enfortumab Vedotin, Biological: Pembrolizumab, Drug: Supportive care measures
Brief Summary
The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435 by itself or when it is combined with other standard medicines that treat cancer. LOXO-435 may be used to treat cancer of the cells that line the urinary system and other solid tumor cancers that have a change in a particular gene (known as the FGFR3 gene). Participation could last up to 30 months (2.5 years) and possibly longer if the disease does not get worse.
Protocol Interventions
Drug: LOXO-435, Drug: Pembrolizumab, Drug: enfortumab vedotin
Brief Summary
The aim of this study is to determine the safety and efficacy of 67Cu-SAR-bisPSMA in participants with PSMA-expressing metastatic castrate resistant prostate cancer.
Protocol Interventions
Drug: 64Cu-SAR-bisPSMA, Drug: 67Cu-SAR-bisPSMA
Brief Summary
This phase III trial tests two questions by two separate comparisons of therapies. The first question is whether enhanced therapy (apalutamide in combination with abiraterone + prednisone) added to standard of care (prostate radiation therapy and short term androgen deprivation) is more effective compared to standard of care alone in patients with prostate cancer who experience biochemical recurrence (a rise in the blood level of prostate specific antigen [PSA] after surgical removal of the prostate cancer).
A second question tests treatment in patients with biochemical recurrence who show prostate cancer spreading outside the pelvis (metastasis) by positron emission tomography (PET) imaging. In these patients, the benefit of adding metastasis-directed radiation to enhanced therapy (apalutamide in combination with abiraterone + prednisone) is tested.
Diagnostic procedures, such as PET, may help doctors look for cancer that has spread to the pelvis. Androgens are hormones that may cause the growth of prostate cancer cells. Apalutamide may help fight prostate cancer by blocking the use of androgens by the tumor cells. Metastasis-directed targeted radiation therapy uses high energy rays to kill tumor cells and shrink tumors that have spread. This trial may help doctors determine if using PET results to deliver more tailored treatment (i.e., adding apalutamide, with or without targeted radiation therapy, to standard of care treatment) works better than standard of care treatment alone in patients with biochemical recurrence of prostate cancer.
Protocol Interventions
Radiation: 3-Dimensional Conformal Radiation Therapy, Drug: Apalutamide, Procedure: Computed Tomography, Drug: Degarelix, Radiation: External Beam Radiation Therapy, Other: Fluciclovine F18, Drug: Goserelin Acetate, Procedure: Intensity-Modulated Proton Therapy, Radiation: Intensity-Modulated Radiation Therapy, Drug: Leuprolide Acetate, Procedure: Magnetic Resonance Imaging, Procedure: Positron Emission Tomography, Other: Quality-of-Life Assessment, Other: Questionnaire Administration, Drug: Relugolix, Radiation: Stereotactic Body Radiation Therapy, Drug: Triptorelin, Radiation: Volume Modulated Arc Therapy
Brief Summary
This phase I/II trial studies the best dose of M3814 when given together with radium-223 dichloride or with radium-223 dichloride and avelumab and to see how well they work in treating patients with castrate-resistant prostate cancer that had spread to other places in the body (metastatic). M3814 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radioactive drugs, such as radium-223 dichloride, may carry radiation directly to tumor cells and not harm normal cells. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This study is being done to find out the better treatment between radium-223 dichloride alone, radium-223 dichloride in combination with M3814, or radium-223 dichloride in combination with both M3814 and avelumab, to lower the chance of prostate cancer growing or spreading in the bone, and if this approach is better or worse than the usual approach for advanced prostate cancer not responsive to hormonal therapy.
Protocol Interventions
Drug: Avelumab, Procedure: Biospecimen Collection, Procedure: Bone Scan, Procedure: Computed Tomography, Procedure: Magnetic Resonance Imaging, Drug: Peposertib, Other: Questionnaire Administration, Radiation: Radium Ra 223 Dichloride
Brief Summary
Upon successful screening and registration, enrollment to a cohort will begin. If DLT criteria are exceeded in a cohort, that cohort will close and will not proceed to Phase 2 of the study. Provided the safety of a cohort is established, enrollment will continue. Within BCG-containing cohorts, treatment will begin at full-dose BCG. If DLT criteria are exceeded with full-dose BCG, a one level dose reduction of BCG will be implemented. If DLT criteria are exceeded with reduced-dose BCG, the BCG-containing cohort will not proceed to Phase 2 of the study
Phase 1 Cohorts:
* Durvalumab Monotherapy (cohort 1); ENROLLMENT COMPLETE
* Durvalumab plus BCG (cohort 2); ENROLLMENT COMPLETE
* Durvalumab plus External Beam Radiotherapy (EBRT) (cohort 3); ENROLLMENT COMPLETE
* Durvalumab plus Intravesical Gemcitabine plus Intravesical Docetaxel (cohort 4); ENROLLMENT COMPLETE
* Durvalumab plus Tremelimumab plus Intravesical Gemcitabine plus Intravesical Docetaxel (cohort 5); ENROLLMENT DID NOT OCCUR
* Intravesical N-803NAI plus Intravesical Gemcitabine (cohort 6)
* Intravesical N-803NAI plus Intravesical Gemcitabine plus Intravesical Docetaxel (cohort 7)
* Subcutaneous N-803NAI plus Intravesical N-803NAI plus Intravesical Gemcitabine plus Intravesical Docetaxel (cohort 8)
If any of the combination regimen cohorts establishes a RP2D in Phase 1 of the study, enrollment to Phase 2 of the study may proceed within the individual phase 2 expansion cohorts defined by patient BCG exposure history. Upon successful screening and registration, Phase 2 subjects will be assigned to one of the treatment arms. Assignment will occur amongst the arms that are open to accrual at the time of subject registration. Phase 2 subjects will be administered treatment at the RP2D’s established for each regimen within Phase 1 of the study.
However, within BCG-containing cohorts, the BCG dose will be reduced to Dose level -1 (1/3rd-dose BCG) even if the RP2D established in the Phase 1 of the study was full-dose BCG. The rationale for this stems from ongoing global BCG supply shortages that have arisen since the launch of the trial and multiple prior clinical trials demonstrating similar efficacy with decreased toxicity when reduced-dose BCG regimens are utilized compared to full-dose BCG therapy. This modification was deemed necessary to facilitate continued enrollment to the study while not sacrificing clinical efficacy or safety. This modification also aligns with recent AUA consensus guidelines on BCG dosing during BCG shortages.
It is anticipated that individual treatment cohorts will be closed and added during the conduct of the study as cohorts complete accrual, individual cohort safety data is analyzed, and new cohorts are added. Enrollment to Phase 2 cohorts will not begin until at least one cohort has successfully established a RP2D in the Phase 1 portion of the study and deemed safe to proceed to the Phase 2 portion of the trial.
Protocol Interventions
Other: To be determined
Brief Summary
This phase II trial studies how well atezolizumab works alone or in combination with etrumadenant or tocilizumab in treating men with localized prostate cancer before radical prostatectomy. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Androgens can cause the growth of prostate cancer cells. IL-6 is expressed by prostate cancer and within the tumor microenvironment and shown to enhance prostate cancer and disease progression. Treatment with an anti-IL-6 antibody such as tocilizumab may inhibit cancer progression. Giving atezolizumab in combination with etrumadenant or tocilizumab may work better in treating prostate cancer.
Protocol Interventions
Drug: Atezolizumab, Drug: Tocilizumab
Brief Summary
This phase II trial studies how well cabozantinib works in combination with nivolumab and ipilimumab in treating patients with rare genitourinary (GU) tumors that has spread from where it first started (primary site) to other places in the body. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib, nivolumab, and ipilimumab may work better in treating patients with genitourinary tumors that have no treatment options compared to giving cabozantinib, nivolumab, or ipilimumab alone.
Protocol Interventions
Procedure: Biospecimen Collection, Procedure: Bone Scan, Drug: Cabozantinib S-malate, Procedure: Computed Tomography, Procedure: Echocardiography Test, Biological: Ipilimumab, Procedure: Magnetic Resonance Imaging, Biological: Nivolumab, Procedure: Positron Emission Tomography
Brief Summary
The purpose of this research study is to learn more about the outcomes and early and late side effects of treating early stage prostate cancer with high dose rate brachytherapy.
Protocol Interventions
Radiation: HDR brachytherapy
