This phase II trial compares the effect of dexamethasone with and without metronidazole in combination with abiraterone on resistance to abiraterone in treating patients with prostate cancer that is growing, spreading, or getting worse (progressive), and that has spread from where it first started (primary site) to other places in the body (metastatic) and that grows and continues to spread despite the surgical removal of the testes or medical intervention to block androgen production (castration resistant). Prostate cancer is the second most common cause of cancer death in men in the United States. Androgen deprivation therapy (ADT), such as abiraterone, is the usual treatment for metastatic prostate cancer. ADT blocks the growth of hormone sensitive prostate tumor cells. While ADT is initially very effective, most tumors adapt to the low hormone environment and become resistant to ADT. This is thought to be due to androgen (a type of hormone) production by the bacteria in the gut. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Metronidazole, an antibacterial, antiprotozoal, and anthelmintic, is a drug used to treat infection. It may block the tumor-associated bacteria in the gut and may help improve response to treatment. Abiraterone, a type of anti-androgen, lowers the amount of testosterone made by the body. This may help stop the growth of tumor cells that need testosterone to grow. Giving dexamethasone with or without metronidazole in combination with abiraterone may reverse resistance to abiraterone in patients with progressive metastatic castration resistant prostate cancer.
Additional locations may be listed on ClinicalTrials.gov for NCT06616597.
Locations matching your search criteria
United States
Maryland
Baltimore
Johns Hopkins University/Sidney Kimmel Cancer CenterStatus: Active
Contact: Catherine Handy Marshall
Phone: 410-955-0231
PRIMARY OBJECTIVE:
I. To estimate the prostate specific antigen (PSA) response rate (PSA^30) within 24 weeks in patients with castration resistant prostate cancer.
SECONDARY OBJECTIVES:
I. To estimate the PSA^30 response rate at 12 and 24 weeks of treatment.
II. To estimate the proportion of patients with PSA progression-free survival (PSA-PFS), defined as the time from initiation of dexamethasone +/- metronidazole until PSA increase of 25%, confirmed with another measurement at least 4 weeks later, and rise greater than 2ng/ml (Prostate Cancer Clinical Trials Working Group 3 [PCWG3]) at 24 weeks.
III. To estimate the proportion of patients without progression (progression-free survival [PFS]), defined as the time to radiographic or clinical progression or death, whichever comes first.
CORRELATIVE/EXPLORATORY OBJECTIVES:
I. To measure changes in fecal desmolase quantification by quantitative polymerase chain reaction (PCR) prior to glucocorticoid switch in both trial arms and at baseline, 1 week after glucocorticoid switch, and then every 6 weeks for 24 weeks or until PSA progression.
II. To measure changes in androgen metabolites (including delta1-adrenosterone [AT], 11beta-hydroxyandrost-4-ene-3,17-dione [11OHAD], testosterone [T], dihydrotestosterone [DHT], androstenedione [AD], dehydroepiandrosterone [DHEA], and progesterone) in fecal, serum, and urine samples at baseline, 1 week after glucocorticoid switch, and then every 6 weeks for 24 weeks or until PSA progression.
III. To measure changes in abiraterone acetate (abiraterone) metabolites in fecal, serum, and urine samples at baseline, 1 week after glucocorticoid switch, and then every 6 weeks for 24 weeks or until PSA progression.
IV. To characterize fecal microbiota profile at baseline, 1 week, 6-week, and 24-week time points.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1: Patients receive abiraterone orally (PO) once daily (QD), dexamethasone PO QD for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo urine and blood sample collection, computed tomography (CT), nuclear medicine (NM) bone scan, and/or prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/CT throughout the study.
ARM 2: Patients receive abiraterone PO QD, dexamethasone PO QD for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive metronidazole PO thrice daily (TID) on days 1-5 of cycle 1. Additionally, patients undergo urine and blood sample collection, CT, NM bone scan, and/or PSMA PET/CT throughout the study.
Lead OrganizationJohns Hopkins University/Sidney Kimmel Cancer Center
Principal InvestigatorCatherine Handy Marshall
