This phase II trial tests how well niraparib and abiraterone acetate plus prednisone works in treating Hispanic/Latino and non-Hispanic Black patients with hormone sensitive prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and has a homologous recombination repair (HRR) gene mutation that is documented to be associated with risk of disease (deleterious). Niraparib is in a category of drugs called poly adenosine diphosphate (ADP) ribose polymerase (PARP) inhibitors. Previous studies show PARP inhibitors to be effective in patients with certain mutations in the HRR pathway, as PARP inhibitors block the HRR pathway that prostate tumor cells use to repair themselves, thereby leading to decreased tumor cell growth and survival. Abiraterone acetate lowers the amount of androgens (male hormones), such as testosterone, made by the body. This may stop the growth of tumor cells that need androgens to grow. The combination of niraparib and abiraterone acetate may work better than either drug alone. Prednisone 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. Usual treatment for prostate cancer includes androgen deprivation therapy (ADT) and sometimes the addition of chemotherapy drugs, such as docetaxel. Docetaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Studies have shown that the level of prostate specific antigen (PSA) decline can indicate how well the tumor is responding to treatment, with lower levels indicating a better response. Giving niraparib and abiraterone acetate plus prednisone in combination with standard of care ADT/docetaxel may be effective in decreasing PSA levels and killing more tumor cells in Hispanic/Latino and non-Hispanic Black patients with metastatic hormone sensitive prostate cancer with a deleterious HRR mutation.
Additional locations may be listed on ClinicalTrials.gov for NCT06392841.
Locations matching your search criteria
United States
Texas
Dallas
UT Southwestern/Simmons Cancer Center-DallasStatus: Active
Contact: Qian Qin
Phone: 212-648-1996
PRIMARY OBJECTIVE:
I. Evaluate PSA decline to < 0.2 ng/ml at 24 weeks of therapy with ADT and abiraterone acetate/niraparib (niraparib/abiraterone acetate [AA] dual action tablet [DAT]) plus prednisone (P).
SECONDARY OBJECTIVES:
I. Evaluate the percentage of subjects with PSA reduction ≥ 90% (PSA90) after 24 weeks of therapy with ADT and niraparib/AA DAT plus P.
II. Evaluate the percentage of subjects with PSA decline to < 0.2 ng/ml at one year.
III. Evaluate overall response rate (ORR).
IV. Evaluate PSA progression free survival (PFS).
V. Evaluate radiographic progression free survival (rPFS).
VI. Evaluate the safety of ADT and niraparib/AA DAT plus P as well as ADT and docetaxel/AA plus P.
CORRELATIVE/EXPLORATORY OBJECTIVES:
I. Evaluate overall survival (OS).
II. Evaluate time to subsequent anti-cancer therapy.
III. For subjects who achieve PSA < 0.2 ng/ml at 1 year and opt to hold treatment, evaluate time to re-initiation of cancer-directed therapy.
IV. Evaluate response difference between BRCA 1/2 versus other HRR mutations.
V. Evaluate response difference between high versus low volume disease subjects.
VI. Evaluate health-related quality of life (HRQoL) per Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire.
VII. Evaluate changes in circulating tumor cell (CTC) enumeration with therapy via evaluation of peripheral blood.
VIII. Evaluate the somatic mutational landscape of Hispanic/Latino and non-Hispanic Black (NHB) subjects via evaluation of archival tumor tissue and/or peripheral blood.
IX. Evaluate genomic polymorphism via evaluation of peripheral blood.
OUTLINE:
Patients receive niraparib/AA DAT orally (PO) once daily (QD) on days 1-28 of each cycle and prednisone PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive gonadotropin-releasing hormone (GnRH) agonist or antagonist per standard of care (SOC).
After completion of cycle 6, patients with PSA > 4 ng/mL are assigned to Cohort A and patients with PSA ≤ 4 are assigned to Cohort B.
COHORT A: Patients may choose 1 of 2 options.
OPTION 1: Patients receive niraparib/AA DAT PO QD on days 1-28 of each cycle and prednisone PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may also receive GnRH agonist or antagonist per SOC.
OPTION 2: Patients receive abiraterone acetate PO QD on days 1-21 of each cycle, prednisone PO QD on days 1-21 of each cycle and docetaxel intravenously (IV) on day 1 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive GnRH agonist or antagonist per SOC.
COHORT B: Patients receive niraparib/AA DAT PO QD on days 1-28 of each cycle and prednisone PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients may also receive GnRH agonist or antagonist per SOC. Patients with a PSA ≥ 0.2 ng/mL then continue receiving niraparib/AA DAT and prednisone for an additional year in the absence of disease progression or unacceptable toxicity. Patients with a PSA < 0.2 ng/mL at 12 months may then choose 1 of 2 options:
OPTION 1: Patients continue to receive niraparib/AA DAT PO QD on days 1-28 and prednisone PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for an additional year in the absence of disease progression or unacceptable toxicity. Patients may also receive GnRH agonist or antagonist per SOC.
OPTION 2: Patients stop niraparib/AA DAT, prednisone, and GnRH agonist or antagonist.
Additionally, patients undergo blood sample collection, bone scan and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study.
After completion of study treatment, patients are followed up at 30 days then every 3 months for up to 2 years from cycle 1 day 1.
Lead OrganizationUT Southwestern/Simmons Cancer Center-Dallas
Principal InvestigatorQian Qin
