SUSPENDED

Niraparib, Abiraterone Acetate and Prednisone for mHSPC With Deleterious Homologous Recombination Repair Alterations

Conditions

Metastatic Hormone-sensitive Prostate Cancer (mHSPC)Deleterious HRR Gene Mutation BRCA1 Gene Mutation BRCA2 Gene Mutation BRIP1 Gene Mutation CHEK2 Gene Mutation FANCA Gene Mutation PALB2 Gene Mutation RAD51B Gene Mutation RAD54L Gene Mutation

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is an open label, phase II trial in subjects with treatment naïve, metastatic hormone sensitive prostate cancer (mHSPC) with deleterious homologous recombination repair (HRR) alteration(s). These include pathologic alterations in BRCA 1/2, BRIP1, CHEK2, FANCA, PALB2, RAD51B, and/or RAD54L. A total of 64 people will be enrolled to the study.

Official Title

Hispanic/Latino and Non-Hispanic BlAck Patients Treated With niRaparib and Abiraterone Acetate Plus Prednisone for Metastatic hOrmone Sensitive Prostate Cancer With Deleterious Homologous recombinatioN Repair Alterations: a Phase II, Open Label studY

Quick Facts

Study Start:2025-10

Study Completion:2028-04

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:SUSPENDED

Study ID

NCT06392841

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:MALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. 2. ≥ 18 years of age at the time of consent. 3. Self-identify as Hispanic/Latino or non-Hispanic black racial/ethnic background. 4. ECOG Performance Status of ≤ 2 within 30 days prior to registration. 5. Histologically confirmed diagnosis of prostate adenocarcinoma. 6. Deleterious HRR alteration(s) per any validated test, next generation sequencing (NGS) mutational analysis (tissue or liquid). These include BRCA 1/2, BRIP1, CHEK2, FANCA, PALB2, RAD51B, and/or RAD54L. 7. Radiographic evidence of metastatic disease as per conventional CT or MRI of chest, abdomen pelvis and bone scan, according to RECIST version 1.1 criteria in subjects with measurable disease and PCWG3 criteria for subjects with bone only disease (1, 2). Evidence of metastatic disease detected on Axumin or PSMA PET/CT will need confirmation on conventional CT or MRI/bone scans. 8. Hormone sensitive, treatment naïve/minimally treated \[first generation androgen receptor inhibitor (ARI) such as bicalutamide ≤ 45 days, ADT ± abiraterone acetate plus prednisone ≤ 45 days allowed\]. Prior therapy for localized prostate cancer allowed (including but not limited to radiation therapy, prostatectomy, lymph node dissection ± ADT, must have been completed \> 6 months prior to registration). 9. Demonstrate adequate organ function as defined below. All screening labs to be obtained within 30 days prior to registration. * Platelets (Plt): ≥ 100 x 10\^9/L (Independent of transfusions for at least 28 days prior to registration) * Absolute Neutrophil Count (ANC): ≥ 1.5 x 10\^9/L (Independent of hematopoietic growth factors for at least 28 days prior to registration) * Hemoglobin (Hgb): ≥ 9 g/dL (Independent of transfusions for at least 28 days prior to registration) * Creatinine: Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min * Total bilirubin: ≤ 1.5 × ULN or direct bilirubin ≤ 1 x ULN (For subjects with Gilbert's syndrome, if total bilirubin is \>1.5 × ULN, measure direct and indirect bilirubin, and if direct bilirubin is ≤1.5 × ULN, subjects may be eligible.) * Aspartate aminotransferase (AST): ≤ 3 × ULN * Alanine aminotransferase (ALT): ≤ 3 × ULN * Serum potassium: ≥ 3.5 mmol/L 10. Males able to father a child who are sexually active with a female of childbearing potential must be willing to abstain from penile-vaginal intercourse or use an effective method(s) of contraception. 11. Able to swallow the study medication tablets whole. 12. Life expectancy ≥ 12 months. 13. 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.	1. Prostate cancer variants including predominant neuroendocrine features and/or predominant small cell carcinoma of the prostate are excluded. 2. Prior treatment with the following is excluded: second generation ARIs such as apalutamide, enzalutamide, darolutamide, or other investigational ARIs; oral ketoconazole as antineoplastic treatment for prostate cancer (allowed if total time on ketoconazole as prostate cancer-directed therapy is ≤ 10 days and discontinued prior to study treatment initiation); chemotherapy or immunotherapy for prostate cancer. 3. Radiotherapy/radiopharmaceuticals within 2 weeks of registration. 4. History of severe allergic anaphylactic reactions to niraparib/abiraterone acetate tablets or any of their excipients. 5. Current evidence of any medical condition that would make prednisone use contraindicated. 6. Long-term use of systemically administered corticosteroids (\> 5mg of prednisone or the equivalent) during the study is not allowed (5mg of prednisone or equivalent daily, given with abiraterone acetate, is allowed). Short-term use of corticosteroid for indication other than in combination with abiraterone acetate (≤ 4 weeks, including taper) and locally administered steroids (eg, inhaled, topical, ophthalmic, and intra-articular) are allowed, if clinically indicated. 7. Subjects who have had major surgery ≤ 28 days prior to registration. 8. Symptomatic brain metastases. 9. Active or symptomatic viral hepatitis or chronic liver disease; encephalopathy, ascites, or bleeding disorders secondary to hepatic dysfunction. 10. Moderate or severe hepatic impairment (Class B and C per Child-Pugh classification system. 11. History of adrenal insufficiency not adequately managed. 12. History or current diagnosis of MDS/AML. 13. Current evidence within 6 months prior to registration of any of the following: * Severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, * Clinically significant arterial or venous thromboembolic events (ie. pulmonary embolism), or clinically significant ventricular arrhythmias. 14. Presence of sustained uncontrolled hypertension (systolic blood pressure \>160 mm Hg or diastolic blood pressure \>100 mm Hg). Subjects with a history of hypertension are allowed, provided that blood pressure is controlled to within these limits by an antihypertensive treatment. 15. Human immunodeficiency virus positive subjects with 1 or more of the following: * Not receiving highly active antiretroviral therapy or on antiretroviral therapy for less than 4 weeks. * Receiving antiretroviral therapy that may interfere with the study medication * CD4 count \<350 at screening. * An acquired immunodeficiency syndrome-defining opportunistic infection within 6 months of the start of screening. * Human immunodeficiency virus load \>400 copies/mL. 16. Active infection requiring systemic therapy. NOTE: Subjects receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study. 17. Active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions are: * Non-muscle invasive bladder cancer. * Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured. * Malignancy that is considered cured with minimal risk of recurrence. 18. Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 30 days prior to C1D1.

Inclusion Criteria

Exclusion Criteria

1. Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
2. ≥ 18 years of age at the time of consent.
3. Self-identify as Hispanic/Latino or non-Hispanic black racial/ethnic background.
4. ECOG Performance Status of ≤ 2 within 30 days prior to registration.
5. Histologically confirmed diagnosis of prostate adenocarcinoma.
6. Deleterious HRR alteration(s) per any validated test, next generation sequencing (NGS) mutational analysis (tissue or liquid). These include BRCA 1/2, BRIP1, CHEK2, FANCA, PALB2, RAD51B, and/or RAD54L.
7. Radiographic evidence of metastatic disease as per conventional CT or MRI of chest, abdomen pelvis and bone scan, according to RECIST version 1.1 criteria in subjects with measurable disease and PCWG3 criteria for subjects with bone only disease (1, 2). Evidence of metastatic disease detected on Axumin or PSMA PET/CT will need confirmation on conventional CT or MRI/bone scans.
8. Hormone sensitive, treatment naïve/minimally treated \[first generation androgen receptor inhibitor (ARI) such as bicalutamide ≤ 45 days, ADT ± abiraterone acetate plus prednisone ≤ 45 days allowed\]. Prior therapy for localized prostate cancer allowed (including but not limited to radiation therapy, prostatectomy, lymph node dissection ± ADT, must have been completed \> 6 months prior to registration).
9. Demonstrate adequate organ function as defined below. All screening labs to be obtained within 30 days prior to registration.
* Platelets (Plt): ≥ 100 x 10\^9/L (Independent of transfusions for at least 28 days prior to registration)
* Absolute Neutrophil Count (ANC): ≥ 1.5 x 10\^9/L (Independent of hematopoietic growth factors for at least 28 days prior to registration)
* Hemoglobin (Hgb): ≥ 9 g/dL (Independent of transfusions for at least 28 days prior to registration)
* Creatinine: Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min
* Total bilirubin: ≤ 1.5 × ULN or direct bilirubin ≤ 1 x ULN (For subjects with Gilbert's syndrome, if total bilirubin is \>1.5 × ULN, measure direct and indirect bilirubin, and if direct bilirubin is ≤1.5 × ULN, subjects may be eligible.)
* Aspartate aminotransferase (AST): ≤ 3 × ULN
* Alanine aminotransferase (ALT): ≤ 3 × ULN
* Serum potassium: ≥ 3.5 mmol/L
10. Males able to father a child who are sexually active with a female of childbearing potential must be willing to abstain from penile-vaginal intercourse or use an effective method(s) of contraception.
11. Able to swallow the study medication tablets whole.
12. Life expectancy ≥ 12 months.
13. 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.

1. Prostate cancer variants including predominant neuroendocrine features and/or predominant small cell carcinoma of the prostate are excluded.
2. Prior treatment with the following is excluded: second generation ARIs such as apalutamide, enzalutamide, darolutamide, or other investigational ARIs; oral ketoconazole as antineoplastic treatment for prostate cancer (allowed if total time on ketoconazole as prostate cancer-directed therapy is ≤ 10 days and discontinued prior to study treatment initiation); chemotherapy or immunotherapy for prostate cancer.
3. Radiotherapy/radiopharmaceuticals within 2 weeks of registration.
4. History of severe allergic anaphylactic reactions to niraparib/abiraterone acetate tablets or any of their excipients.
5. Current evidence of any medical condition that would make prednisone use contraindicated.
6. Long-term use of systemically administered corticosteroids (\> 5mg of prednisone or the equivalent) during the study is not allowed (5mg of prednisone or equivalent daily, given with abiraterone acetate, is allowed). Short-term use of corticosteroid for indication other than in combination with abiraterone acetate (≤ 4 weeks, including taper) and locally administered steroids (eg, inhaled, topical, ophthalmic, and intra-articular) are allowed, if clinically indicated.
7. Subjects who have had major surgery ≤ 28 days prior to registration.
8. Symptomatic brain metastases.
9. Active or symptomatic viral hepatitis or chronic liver disease; encephalopathy, ascites, or bleeding disorders secondary to hepatic dysfunction.
10. Moderate or severe hepatic impairment (Class B and C per Child-Pugh classification system.
11. History of adrenal insufficiency not adequately managed.
12. History or current diagnosis of MDS/AML.
13. Current evidence within 6 months prior to registration of any of the following:
* Severe/unstable angina, myocardial infarction, symptomatic congestive heart failure,
* Clinically significant arterial or venous thromboembolic events (ie. pulmonary embolism), or clinically significant ventricular arrhythmias.
14. Presence of sustained uncontrolled hypertension (systolic blood pressure \>160 mm Hg or diastolic blood pressure \>100 mm Hg). Subjects with a history of hypertension are allowed, provided that blood pressure is controlled to within these limits by an antihypertensive treatment.
15. Human immunodeficiency virus positive subjects with 1 or more of the following:
* Not receiving highly active antiretroviral therapy or on antiretroviral therapy for less than 4 weeks.
* Receiving antiretroviral therapy that may interfere with the study medication
* CD4 count \<350 at screening.
* An acquired immunodeficiency syndrome-defining opportunistic infection within 6 months of the start of screening.
* Human immunodeficiency virus load \>400 copies/mL.
16. Active infection requiring systemic therapy. NOTE: Subjects receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
17. Active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions are:
* Non-muscle invasive bladder cancer.
* Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured.
* Malignancy that is considered cured with minimal risk of recurrence.
18. Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 30 days prior to C1D1.

Contacts and Locations

Principal Investigator

Qian Qin, MD

PRINCIPAL_INVESTIGATOR

UT Southwestern Comprehensive Cancer Center

Study Locations (Sites)

University of Illinois Cancer Center

Chicago, Illinois, 60612

United States

University of Texas Southwestern Medical Center

Dallas, Texas, 75390

United States

Collaborators and Investigators

Sponsor: Qian Qin

Qian Qin, MD, PRINCIPAL_INVESTIGATOR, UT Southwestern Comprehensive Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-10

Study Completion Date2028-04

Study Record Updates

Study Start Date2025-10

Study Completion Date2028-04

Terms related to this study

Additional Relevant MeSH Terms

Metastatic Hormone-sensitive Prostate Cancer (mHSPC)
Deleterious HRR Gene Mutation
BRCA1 Gene Mutation
BRCA2 Gene Mutation
BRIP1 Gene Mutation
CHEK2 Gene Mutation
FANCA Gene Mutation
PALB2 Gene Mutation
RAD51B Gene Mutation
RAD54L Gene Mutation