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The clinical trials listed below are open as of March 10, 2025; have ≥ 1 US Department of Veterans Affairs (VA) medical center (VAMC) or US Department of Defense (DoD) military treatment facility location recruiting patients; and are focused on treatments for chronic obstructive pulmonary disease (COPD). For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.
Actively Recruiting
Patient Decision-making About Precision Oncology in Veterans With Advanced Prostate Cancer
This clinical trial explores and implements methods to improve informed decision making (IDM) regarding precision oncology tests amongst veterans with prostate cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Precision oncology, the use of germline genetic testing and tumor-based molecular assays to inform cancer care, has become an important aspect of evidence-based care for men with advanced prostate cancer. Veterans with metastatic castrate-resistant prostate cancer may not be carrying out IDM due to unmet decisional needs. An informed decision is a choice based on complete and accurate information. The information gained from this study will help researchers develop a decision support intervention (DSI) and implement the intervention. A DSI may serve as a valuable tool to reduce ongoing racial disparities in genetic testing and encourage enrollment to precision oncology trials.
ID: NCT05396872
Sponsor; Investigator; Collaborator: University of California, San Francisco; Daniel Kwon, MD; US Department of Defense VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: San Francisco Veterans Affairs Medical Center, CA
Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for Oligometastatic pRosTate Cancer (VA STARPORT)
This is a prospective, open-label, multi-center seamless phase II to phase III randomized clinical trial designed to compare SST with or without PET-directed local therapy in improving the castration-resistant prostate cancer-free survival (CRPC-free survival) for veterans with oligometastatic prostate cancer. Oligometastasis will be defined as 1-10 sites of metastatic disease based on the clinical determination of the LSI which incorporates all imaging, clinical, and pathologic data available.
ID: NCT04787744
Sponsor; Collaborator: VA Office of Research and Development; Abhishek Solanki, MD, MS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 19 locations, including Edwards Hines Jr. VA Hospital, Hines, IL
The Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS) (ProGRESS)
Prostate cancer is the most common non-skin cancer among veterans and the second leading cause of male cancer death. Current methods of screening men for prostate cancer are inaccurate and cannot identify which men do not have prostate cancer or have low-grade cases that will not cause harm and which men have significant prostate cancer needing treatment. False-positive screening tests can result in unnecessary prostate biopsies for men who do not need them. However, new genetic testing might help identify which men are at highest risk for prostate cancer. This study will examine whether a genetic test helps identify men at risk for significant prostate cancer while helping men who are at low risk for prostate cancer avoid unnecessary biopsies. If this genetic test proves beneficial, it will improve the way that health care providers screen male veterans for prostate cancer.
ID: NCT05926102
Sponsor; Collaborator: VA Office of Research and Development; Jason L. Vassy, MD, MPH VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Boston Healthcare System Jamaica Plain Campus, MA
A Single-Arm Phase II Study of Neoadjuvant Intensified Androgen Deprivation (Leuprolide and Abiraterone Acetate) in Combination With AKT Inhibition (Capivasertib) for High-Risk Localized Prostate Cancer With PTEN Loss (SNARE)
The purpose of this study is to learn about how an investigational drug intervention completed before doing prostate surgery (specifically, radical prostatectomy with lymph node dissection) may help in treatment of high risk localized prostate cancers that are most resistant to standard treatments. This is a phase II research study. For this study, capivasertib, the study drug, will be taken with intensified androgen deprivation drugs (iADT; abiraterone and leuprolide) prior to radical prostatectomy. This study drug treatment will be evaluated to see if it is effective in shrinking and destroying prostate cancer tumors prior to surgery and to further evaluate its safety prior to prostate cancer surgery.
ID: NCT05593497
Sponsor; Collaborator: VA Office of Research and Development; Ryan P. Kopp, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 5 locations, including VA Portland Health Care System, OR
18F-Fluciclovine PET/CT Impact on Predicting Clinical Outcome of 177Lu-PSMA-617 Therapy in Patients With Prostate Cancer
This is a single-center, prospective, exploratory study. Patients with metastatic castration-resistant prostate cancer (mCRPC) scheduled to undergo Lutetium labelled prostate-specific membrane antigen radioligand therapy (LuPSMA RLT) at the West Los Angeles VA (WLA-VA) will be imaged with a baseline F-18 fluorodeoxyglucose positron emission tomography/computed tomography 18F-FDG PET/CT and a 18F-DCFPyL PET/CT (18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid)positron emission tomography/computed tomography , as per standard of care in our institution. All patients further undergo eventual follow-up prostate-specific membrane antigen positron emission tomography (PSMA PET) after the 2nd, 4th, and 6th LuPSMA RLT cycle. In this prospective study, an18F-Fluciclovine positron emission tomography/computed tomography (Axumin PET/CT) will be additionally obtained at baseline (pre-LuPSMA RLT), and after the 2nd, 4th, 6th LuPSMA RLT cycles. Axumin PET/CT will be acquired within 7 days from the PSMA PET.
This study is open to veterans only.
ID: NCT06706921
Sponsor; Collaborator: VA Greater Los Angeles Healthcare System; Gholam Berenji, MD, Janake Wijesuriya, BS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Greater Los Angeles Healthcare System, CA
High Dose Testosterone for ATM, CDK12 or CHEK2 Altered Prostate Cancers (VA-BAT)
This study will determine whether the presence of DNA repair deficiency in the form of alterations in the genes ATM, CDK12 or CHEK2 predicts for a high likelihood of responding to the use of intermittent high dose testosterone. This therapy may result in responses in tumors which are genetically unstable because of DNA repair deficiency and this is a prospective study to test that hypothesis.
ID: NCT05011383
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA
A Study of CHeckpoint Inhibitors in Men With prOgressive Metastatic Castrate Resistant Prostate Cancer Characterized by a Mismatch Repair Deficiency or Biallelic CDK12 Inactivation (CHOMP)
The primary objective is to assess the activity and efficacy of pembrolizumab, a checkpoint inhibitor, in veterans with metastatic castration-resistant prostate cancer (mCRPC) characterized by either mismatch repair deficiency (dMMR) or biallelic inactivation of CDK12 (CDK12-/-). The secondary objectives involve determining the frequency with which dMMR and CDK12-/- occur in this patient population, as well as the effects of pembrolizumab on various clinical endpoints (time to PSA progression, maximal PSA response, time to initiation of alternative anti-neoplastic therapy, time to radiographic progression, overall survival, and safety and tolerability). Lastly, the study will compare the pre-treatment and at-progression metastatic tumor biopsies to investigate the molecular correlates of resistance and sensitivity to pembrolizumab via RNA-sequencing, exome-sequencing, selected protein analyses, and multiplexed immunofluorescence.
ID: NCT04104893
Sponsor; Investigator; Collaborator: VA Office of Research and Development; Matthew B. Rettig, MD; Merck Sharp & Dohme LLC VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 12 locations, including VA Greater Los Angeles Healthcare System, CA
Carboplatin or Olaparib for BRcA Deficient Prostate Cancer (COBRA)
This is an unblinded, randomized clinical study comparing the efficacy of DNA damaging chemotherapy using carboplatin, to standard of care therapy for patients who have metastatic castrate resistant prostate cancer. This trial will use olaparib or carboplatin as initial therapy with crossover to the alternate or second-line drug after first progression for patients with tumors containing BARD1, BRCA1, BRCA2, BRIP1, CHEK1, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L inactivating mutations.
Participants are randomized (1:1) and receive either carboplatin (AUC 5, IV) every 21 days, first or olaparib taken orally (300 mg), twice daily in 28-day cycles, until intolerance, complete response, or progression by Prostate Cancer Working Group 3 (PCWG3) criteria.
Participants then cross over from the first-line therapy to the second-line therapy with the opposite study medication and receive treatment to intolerance or progression (whichever is first). Enrolled participants will be allowed to crossover to second line therapy if they continue to meet initial eligibility criteria, and at least three weeks have elapsed since last administration of either carboplatin or olaparib. Throughout the study, safety and tolerability will be assessed. Progression will be evaluated with bone scan, CT of the abdomen/pelvis, or MRI and PSA as per PCWG3 criteria.
ID: NCT04038502
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD; Ryan Burri, MD; Phoebe Tsao, MD, MSc; Maneesh Jain, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA
The clinical trials listed below are open as of March 10, 2025; have ≥ 1 US Department of Veterans Affairs (VA) medical center (VAMC) or US Department of Defense (DoD) military treatment facility location recruiting patients; and are focused on treatments for chronic obstructive pulmonary disease (COPD). For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.
Actively Recruiting
Patient Decision-making About Precision Oncology in Veterans With Advanced Prostate Cancer
This clinical trial explores and implements methods to improve informed decision making (IDM) regarding precision oncology tests amongst veterans with prostate cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Precision oncology, the use of germline genetic testing and tumor-based molecular assays to inform cancer care, has become an important aspect of evidence-based care for men with advanced prostate cancer. Veterans with metastatic castrate-resistant prostate cancer may not be carrying out IDM due to unmet decisional needs. An informed decision is a choice based on complete and accurate information. The information gained from this study will help researchers develop a decision support intervention (DSI) and implement the intervention. A DSI may serve as a valuable tool to reduce ongoing racial disparities in genetic testing and encourage enrollment to precision oncology trials.
ID: NCT05396872
Sponsor; Investigator; Collaborator: University of California, San Francisco; Daniel Kwon, MD; US Department of Defense VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: San Francisco Veterans Affairs Medical Center, CA
Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for Oligometastatic pRosTate Cancer (VA STARPORT)
This is a prospective, open-label, multi-center seamless phase II to phase III randomized clinical trial designed to compare SST with or without PET-directed local therapy in improving the castration-resistant prostate cancer-free survival (CRPC-free survival) for veterans with oligometastatic prostate cancer. Oligometastasis will be defined as 1-10 sites of metastatic disease based on the clinical determination of the LSI which incorporates all imaging, clinical, and pathologic data available.
ID: NCT04787744
Sponsor; Collaborator: VA Office of Research and Development; Abhishek Solanki, MD, MS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 19 locations, including Edwards Hines Jr. VA Hospital, Hines, IL
The Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS) (ProGRESS)
Prostate cancer is the most common non-skin cancer among veterans and the second leading cause of male cancer death. Current methods of screening men for prostate cancer are inaccurate and cannot identify which men do not have prostate cancer or have low-grade cases that will not cause harm and which men have significant prostate cancer needing treatment. False-positive screening tests can result in unnecessary prostate biopsies for men who do not need them. However, new genetic testing might help identify which men are at highest risk for prostate cancer. This study will examine whether a genetic test helps identify men at risk for significant prostate cancer while helping men who are at low risk for prostate cancer avoid unnecessary biopsies. If this genetic test proves beneficial, it will improve the way that health care providers screen male veterans for prostate cancer.
ID: NCT05926102
Sponsor; Collaborator: VA Office of Research and Development; Jason L. Vassy, MD, MPH VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Boston Healthcare System Jamaica Plain Campus, MA
A Single-Arm Phase II Study of Neoadjuvant Intensified Androgen Deprivation (Leuprolide and Abiraterone Acetate) in Combination With AKT Inhibition (Capivasertib) for High-Risk Localized Prostate Cancer With PTEN Loss (SNARE)
The purpose of this study is to learn about how an investigational drug intervention completed before doing prostate surgery (specifically, radical prostatectomy with lymph node dissection) may help in treatment of high risk localized prostate cancers that are most resistant to standard treatments. This is a phase II research study. For this study, capivasertib, the study drug, will be taken with intensified androgen deprivation drugs (iADT; abiraterone and leuprolide) prior to radical prostatectomy. This study drug treatment will be evaluated to see if it is effective in shrinking and destroying prostate cancer tumors prior to surgery and to further evaluate its safety prior to prostate cancer surgery.
ID: NCT05593497
Sponsor; Collaborator: VA Office of Research and Development; Ryan P. Kopp, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 5 locations, including VA Portland Health Care System, OR
18F-Fluciclovine PET/CT Impact on Predicting Clinical Outcome of 177Lu-PSMA-617 Therapy in Patients With Prostate Cancer
This is a single-center, prospective, exploratory study. Patients with metastatic castration-resistant prostate cancer (mCRPC) scheduled to undergo Lutetium labelled prostate-specific membrane antigen radioligand therapy (LuPSMA RLT) at the West Los Angeles VA (WLA-VA) will be imaged with a baseline F-18 fluorodeoxyglucose positron emission tomography/computed tomography 18F-FDG PET/CT and a 18F-DCFPyL PET/CT (18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid)positron emission tomography/computed tomography , as per standard of care in our institution. All patients further undergo eventual follow-up prostate-specific membrane antigen positron emission tomography (PSMA PET) after the 2nd, 4th, and 6th LuPSMA RLT cycle. In this prospective study, an18F-Fluciclovine positron emission tomography/computed tomography (Axumin PET/CT) will be additionally obtained at baseline (pre-LuPSMA RLT), and after the 2nd, 4th, 6th LuPSMA RLT cycles. Axumin PET/CT will be acquired within 7 days from the PSMA PET.
This study is open to veterans only.
ID: NCT06706921
Sponsor; Collaborator: VA Greater Los Angeles Healthcare System; Gholam Berenji, MD, Janake Wijesuriya, BS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Greater Los Angeles Healthcare System, CA
High Dose Testosterone for ATM, CDK12 or CHEK2 Altered Prostate Cancers (VA-BAT)
This study will determine whether the presence of DNA repair deficiency in the form of alterations in the genes ATM, CDK12 or CHEK2 predicts for a high likelihood of responding to the use of intermittent high dose testosterone. This therapy may result in responses in tumors which are genetically unstable because of DNA repair deficiency and this is a prospective study to test that hypothesis.
ID: NCT05011383
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA
A Study of CHeckpoint Inhibitors in Men With prOgressive Metastatic Castrate Resistant Prostate Cancer Characterized by a Mismatch Repair Deficiency or Biallelic CDK12 Inactivation (CHOMP)
The primary objective is to assess the activity and efficacy of pembrolizumab, a checkpoint inhibitor, in veterans with metastatic castration-resistant prostate cancer (mCRPC) characterized by either mismatch repair deficiency (dMMR) or biallelic inactivation of CDK12 (CDK12-/-). The secondary objectives involve determining the frequency with which dMMR and CDK12-/- occur in this patient population, as well as the effects of pembrolizumab on various clinical endpoints (time to PSA progression, maximal PSA response, time to initiation of alternative anti-neoplastic therapy, time to radiographic progression, overall survival, and safety and tolerability). Lastly, the study will compare the pre-treatment and at-progression metastatic tumor biopsies to investigate the molecular correlates of resistance and sensitivity to pembrolizumab via RNA-sequencing, exome-sequencing, selected protein analyses, and multiplexed immunofluorescence.
ID: NCT04104893
Sponsor; Investigator; Collaborator: VA Office of Research and Development; Matthew B. Rettig, MD; Merck Sharp & Dohme LLC VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 12 locations, including VA Greater Los Angeles Healthcare System, CA
Carboplatin or Olaparib for BRcA Deficient Prostate Cancer (COBRA)
This is an unblinded, randomized clinical study comparing the efficacy of DNA damaging chemotherapy using carboplatin, to standard of care therapy for patients who have metastatic castrate resistant prostate cancer. This trial will use olaparib or carboplatin as initial therapy with crossover to the alternate or second-line drug after first progression for patients with tumors containing BARD1, BRCA1, BRCA2, BRIP1, CHEK1, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L inactivating mutations.
Participants are randomized (1:1) and receive either carboplatin (AUC 5, IV) every 21 days, first or olaparib taken orally (300 mg), twice daily in 28-day cycles, until intolerance, complete response, or progression by Prostate Cancer Working Group 3 (PCWG3) criteria.
Participants then cross over from the first-line therapy to the second-line therapy with the opposite study medication and receive treatment to intolerance or progression (whichever is first). Enrolled participants will be allowed to crossover to second line therapy if they continue to meet initial eligibility criteria, and at least three weeks have elapsed since last administration of either carboplatin or olaparib. Throughout the study, safety and tolerability will be assessed. Progression will be evaluated with bone scan, CT of the abdomen/pelvis, or MRI and PSA as per PCWG3 criteria.
ID: NCT04038502
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD; Ryan Burri, MD; Phoebe Tsao, MD, MSc; Maneesh Jain, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA
The clinical trials listed below are open as of March 10, 2025; have ≥ 1 US Department of Veterans Affairs (VA) medical center (VAMC) or US Department of Defense (DoD) military treatment facility location recruiting patients; and are focused on treatments for chronic obstructive pulmonary disease (COPD). For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.
Actively Recruiting
Patient Decision-making About Precision Oncology in Veterans With Advanced Prostate Cancer
This clinical trial explores and implements methods to improve informed decision making (IDM) regarding precision oncology tests amongst veterans with prostate cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Precision oncology, the use of germline genetic testing and tumor-based molecular assays to inform cancer care, has become an important aspect of evidence-based care for men with advanced prostate cancer. Veterans with metastatic castrate-resistant prostate cancer may not be carrying out IDM due to unmet decisional needs. An informed decision is a choice based on complete and accurate information. The information gained from this study will help researchers develop a decision support intervention (DSI) and implement the intervention. A DSI may serve as a valuable tool to reduce ongoing racial disparities in genetic testing and encourage enrollment to precision oncology trials.
ID: NCT05396872
Sponsor; Investigator; Collaborator: University of California, San Francisco; Daniel Kwon, MD; US Department of Defense VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: San Francisco Veterans Affairs Medical Center, CA
Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for Oligometastatic pRosTate Cancer (VA STARPORT)
This is a prospective, open-label, multi-center seamless phase II to phase III randomized clinical trial designed to compare SST with or without PET-directed local therapy in improving the castration-resistant prostate cancer-free survival (CRPC-free survival) for veterans with oligometastatic prostate cancer. Oligometastasis will be defined as 1-10 sites of metastatic disease based on the clinical determination of the LSI which incorporates all imaging, clinical, and pathologic data available.
ID: NCT04787744
Sponsor; Collaborator: VA Office of Research and Development; Abhishek Solanki, MD, MS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 19 locations, including Edwards Hines Jr. VA Hospital, Hines, IL
The Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS) (ProGRESS)
Prostate cancer is the most common non-skin cancer among veterans and the second leading cause of male cancer death. Current methods of screening men for prostate cancer are inaccurate and cannot identify which men do not have prostate cancer or have low-grade cases that will not cause harm and which men have significant prostate cancer needing treatment. False-positive screening tests can result in unnecessary prostate biopsies for men who do not need them. However, new genetic testing might help identify which men are at highest risk for prostate cancer. This study will examine whether a genetic test helps identify men at risk for significant prostate cancer while helping men who are at low risk for prostate cancer avoid unnecessary biopsies. If this genetic test proves beneficial, it will improve the way that health care providers screen male veterans for prostate cancer.
ID: NCT05926102
Sponsor; Collaborator: VA Office of Research and Development; Jason L. Vassy, MD, MPH VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Boston Healthcare System Jamaica Plain Campus, MA
A Single-Arm Phase II Study of Neoadjuvant Intensified Androgen Deprivation (Leuprolide and Abiraterone Acetate) in Combination With AKT Inhibition (Capivasertib) for High-Risk Localized Prostate Cancer With PTEN Loss (SNARE)
The purpose of this study is to learn about how an investigational drug intervention completed before doing prostate surgery (specifically, radical prostatectomy with lymph node dissection) may help in treatment of high risk localized prostate cancers that are most resistant to standard treatments. This is a phase II research study. For this study, capivasertib, the study drug, will be taken with intensified androgen deprivation drugs (iADT; abiraterone and leuprolide) prior to radical prostatectomy. This study drug treatment will be evaluated to see if it is effective in shrinking and destroying prostate cancer tumors prior to surgery and to further evaluate its safety prior to prostate cancer surgery.
ID: NCT05593497
Sponsor; Collaborator: VA Office of Research and Development; Ryan P. Kopp, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 5 locations, including VA Portland Health Care System, OR
18F-Fluciclovine PET/CT Impact on Predicting Clinical Outcome of 177Lu-PSMA-617 Therapy in Patients With Prostate Cancer
This is a single-center, prospective, exploratory study. Patients with metastatic castration-resistant prostate cancer (mCRPC) scheduled to undergo Lutetium labelled prostate-specific membrane antigen radioligand therapy (LuPSMA RLT) at the West Los Angeles VA (WLA-VA) will be imaged with a baseline F-18 fluorodeoxyglucose positron emission tomography/computed tomography 18F-FDG PET/CT and a 18F-DCFPyL PET/CT (18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid)positron emission tomography/computed tomography , as per standard of care in our institution. All patients further undergo eventual follow-up prostate-specific membrane antigen positron emission tomography (PSMA PET) after the 2nd, 4th, and 6th LuPSMA RLT cycle. In this prospective study, an18F-Fluciclovine positron emission tomography/computed tomography (Axumin PET/CT) will be additionally obtained at baseline (pre-LuPSMA RLT), and after the 2nd, 4th, 6th LuPSMA RLT cycles. Axumin PET/CT will be acquired within 7 days from the PSMA PET.
This study is open to veterans only.
ID: NCT06706921
Sponsor; Collaborator: VA Greater Los Angeles Healthcare System; Gholam Berenji, MD, Janake Wijesuriya, BS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Greater Los Angeles Healthcare System, CA
High Dose Testosterone for ATM, CDK12 or CHEK2 Altered Prostate Cancers (VA-BAT)
This study will determine whether the presence of DNA repair deficiency in the form of alterations in the genes ATM, CDK12 or CHEK2 predicts for a high likelihood of responding to the use of intermittent high dose testosterone. This therapy may result in responses in tumors which are genetically unstable because of DNA repair deficiency and this is a prospective study to test that hypothesis.
ID: NCT05011383
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA
A Study of CHeckpoint Inhibitors in Men With prOgressive Metastatic Castrate Resistant Prostate Cancer Characterized by a Mismatch Repair Deficiency or Biallelic CDK12 Inactivation (CHOMP)
The primary objective is to assess the activity and efficacy of pembrolizumab, a checkpoint inhibitor, in veterans with metastatic castration-resistant prostate cancer (mCRPC) characterized by either mismatch repair deficiency (dMMR) or biallelic inactivation of CDK12 (CDK12-/-). The secondary objectives involve determining the frequency with which dMMR and CDK12-/- occur in this patient population, as well as the effects of pembrolizumab on various clinical endpoints (time to PSA progression, maximal PSA response, time to initiation of alternative anti-neoplastic therapy, time to radiographic progression, overall survival, and safety and tolerability). Lastly, the study will compare the pre-treatment and at-progression metastatic tumor biopsies to investigate the molecular correlates of resistance and sensitivity to pembrolizumab via RNA-sequencing, exome-sequencing, selected protein analyses, and multiplexed immunofluorescence.
ID: NCT04104893
Sponsor; Investigator; Collaborator: VA Office of Research and Development; Matthew B. Rettig, MD; Merck Sharp & Dohme LLC VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 12 locations, including VA Greater Los Angeles Healthcare System, CA
Carboplatin or Olaparib for BRcA Deficient Prostate Cancer (COBRA)
This is an unblinded, randomized clinical study comparing the efficacy of DNA damaging chemotherapy using carboplatin, to standard of care therapy for patients who have metastatic castrate resistant prostate cancer. This trial will use olaparib or carboplatin as initial therapy with crossover to the alternate or second-line drug after first progression for patients with tumors containing BARD1, BRCA1, BRCA2, BRIP1, CHEK1, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L inactivating mutations.
Participants are randomized (1:1) and receive either carboplatin (AUC 5, IV) every 21 days, first or olaparib taken orally (300 mg), twice daily in 28-day cycles, until intolerance, complete response, or progression by Prostate Cancer Working Group 3 (PCWG3) criteria.
Participants then cross over from the first-line therapy to the second-line therapy with the opposite study medication and receive treatment to intolerance or progression (whichever is first). Enrolled participants will be allowed to crossover to second line therapy if they continue to meet initial eligibility criteria, and at least three weeks have elapsed since last administration of either carboplatin or olaparib. Throughout the study, safety and tolerability will be assessed. Progression will be evaluated with bone scan, CT of the abdomen/pelvis, or MRI and PSA as per PCWG3 criteria.
ID: NCT04038502
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD; Ryan Burri, MD; Phoebe Tsao, MD, MSc; Maneesh Jain, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA