Niraparib + Abiraterone Acetate + Prednisone for Prostate Cancer
(HARMONY Trial)
Recruiting in Palo Alto (17 mi)
Overseen ByQian Qin, MD
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Qian Qin
Must not be taking: Second generation ARIs, Chemotherapy
Disqualifiers: Neuroendocrine features, Brain metastases, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?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.
Do I need to stop my current medications to join the trial?
The trial does not specify if you need to stop your current medications, but it does allow short-term use of corticosteroids and requires that long-term use of certain corticosteroids be avoided. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug combination of Niraparib, Abiraterone Acetate, and Prednisone for prostate cancer?
Research shows that Abiraterone Acetate combined with Prednisone improves survival in men with metastatic castration-resistant prostate cancer, suggesting potential benefits when used with other drugs like Niraparib.
12345Is the combination of Niraparib, Abiraterone Acetate, and Prednisone safe for humans?
The combination of Niraparib with Abiraterone Acetate and Prednisone has been studied in patients with prostate cancer and is generally considered to have a manageable safety profile. Abiraterone Acetate with Prednisone is well tolerated, though it can cause known side effects like liver issues and effects related to hormone changes. Niraparib has been shown to be safe when used with these drugs in prostate cancer patients.
678910How is the drug combination of Niraparib, Abiraterone Acetate, and Prednisone unique for prostate cancer?
This drug combination is unique because it combines Niraparib, a PARP inhibitor (a type of drug that blocks certain enzymes involved in repairing damaged DNA), with Abiraterone Acetate and Prednisone, which are already used to treat prostate cancer by blocking androgen production. This combination may offer a novel approach by targeting cancer cells in multiple ways, potentially improving treatment outcomes.
14111213Eligibility Criteria
This trial is for men aged 18+ with newly diagnosed metastatic hormone-sensitive prostate cancer and specific genetic alterations (like BRCA1/2, PALB2). Participants must have minimal prior treatment, adequate organ function, and an ECOG Performance Status of ≤ 2. It's open to Hispanic/Latino or non-Hispanic black individuals.Inclusion Criteria
I have signed the consent form and agreed to share my health information.
I am 18 years old or older.
I identify as Hispanic/Latino or non-Hispanic black.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Initial Treatment
Participants receive ADT with a GnRH agonist or antagonist, 200 mg niraparib, 1,000 mg abiraterone acetate, and 5 mg prednisone daily for 24 weeks (6 cycles) unless there is progression or unacceptable toxicity.
24 weeks
Cohort B Treatment Extension
Participants with PSA ≤ 4 ng/mL without progression continue ADT + niraparib/abiraterone acetate plus prednisone for 1 year unless progression or unacceptable toxicity.
1 year
Cohort A Treatment Extension
Participants with PSA > 4 ng/mL without progression have the option to continue ADT + niraparib/abiraterone acetate plus prednisone for 2 years or switch to ADT, abiraterone acetate plus prednisone, and docetaxel for 6 doses.
2 years
Follow-up
Participants are monitored for safety and effectiveness after treatment completion.
4 years
Participant Groups
The study tests Niraparib combined with Abiraterone Acetate and Prednisone in patients who haven't had extensive previous treatments. The goal is to see how well this combination works on prostate cancer with certain genetic changes related to DNA repair.
3Treatment groups
Experimental Treatment
Group I: Initial Treatment (Cycle 1 to Cycle 6)Experimental Treatment3 Interventions
Androgen Deprivation Therapy (ADT) with a GnRH agonist or antagonist per standard of care. 200 mg niraparib and 1,000 mg abiraterone acetate dual action tablet (DAT, Akeega) once daily, with 5mg prednisone once daily for 24 weeks (6 cycles) unless there is progression or unacceptable toxicity. After 6 cycles, disease evaluation performed.
Group II: Cohort B: PSA ≤ 4 ng/mL without progression at the completion of 24 weeksExperimental Treatment3 Interventions
Continue ADT + niraparib/abiraterone acetate plus prednisone for 1 year unless progression or unacceptable toxicity. At 1 year, disease evaluation will occur.
* PSA ≥ 0.2 ng/mL: ADT + niraparib/abiraterone acetate plus prednisone will continue for 2 years or until progression or unacceptable toxicity. Therapy beyond 2 years will be per standard of care per investigator discretion.
* PSA \< 0.2 ng/mL and PSA not trending up:
1. Continue ADT + niraparib/abiraterone acetate plus prednisone for 2 years or until progression or unacceptable toxicity. Therapy beyond 2 years will be per standard of care per investigator discretion OR
2. STOP ADT + niraparib/abiraterone acetate plus prednisone only IF:
* C14 PSA \< 0.2 AND not trending up
* Subjects not eligible that elect to stop ADT + niraparib/abiraterone acetate plus prednisone, will be removed from protocol treatment and move to follow-up. Subsequent therapy re-initiation will be at the discretion per standard of care.
Group III: Cohort A: prostate specific antigen (PSA) >4 ng/mL without progression at the completion of 24 weeksExperimental Treatment5 Interventions
After 6 cycles, there will be an option to:
1. Continue ADT + niraparib/abiraterone acetate plus prednisone in 28-day cycles for a total of 2 years OR until disease progression or unacceptable toxicity. Subsequent therapy will be at the discretion of the investigator per standard of care.
2. Discontinue niraparib. Continue ADT, start abiraterone acetate plus prednisone and docetaxel 75mg/m2 in 21-day cycles. Docetaxel every 3 weeks x 6 doses. At the completion of docetaxel, the subject will move to follow-up per protocol. Niraparib should not be restarted at the completion of docetaxel. Subsequent therapy will be at the discretion of the investigator per standard of care.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Texas Southwestern Medical CenterDallas, TX
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Who Is Running the Clinical Trial?
Qian QinLead Sponsor
UT Southwestern Comprehensive Cancer CenterCollaborator
Janssen, LPIndustry Sponsor
References
Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. [2022]Abiraterone acetate plus prednisone significantly improved radiographic progression-free survival compared with placebo plus prednisone in men with chemotherapy-naive castration-resistant prostate cancer at the interim analyses of the COU-AA-302 trial. Here, we present the prespecified final analysis of the trial, assessing the effect of abiraterone acetate plus prednisone on overall survival, time to opiate use, and use of other subsequent therapies.
Real-world survival outcome comparing abiraterone acetate plus prednisone and enzalutamide for nonmetastatic castration-resistant prostate cancer. [2023]There is little evidence of abiraterone acetate (AA) plus prednisone for patients with non-metastatic castration-resistant prostate cancer (nmCRPC). In this study, we conducted a comparative analysis of real-world survival outcomes between AA plus prednisone and enzalutamide (Enz) in patients with nmCRPC, utilizing our consortium dataset.
High-Dose Abiraterone Acetate in Men With Castration Resistant Prostate Cancer. [2018]Abiraterone acetate (AA) inhibits androgen biosynthesis and prolongs survival in men with metastatic castration-resistant prostate cancer (mCRPC) when combined with prednisone (P). Resistance to therapy remains incompletely understood. In this open-label, single-arm, multicenter phase II study we investigated the clinical benefit of increasing the dose of AA at the time of resistance to standard-dose therapy.
Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. [2022]Abiraterone acetate, a drug that blocks endogenous androgen synthesis, plus prednisone is indicated for metastatic castration-resistant prostate cancer. We evaluated the clinical benefit of abiraterone acetate plus prednisone with androgen-deprivation therapy in patients with newly diagnosed, metastatic, castration-sensitive prostate cancer.
PSA Kinetics as Prognostic Markers of Overall Survival in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Abiraterone Acetate. [2022]Abiraterone acetate (AA) is widely used in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). However, a significant percentage of patients will still progress, highlighting the need to identify patients more likely to benefit from AA. Parameters linked to prostate-specific antigen (PSA) kinetics are promising prognostic markers. We have examined clinical and PSA-related factors potentially associated with overall survival (OS) in patients treated with AA.
Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE). [2021]To assess the safety and pharmacokinetics and determine the recommended phase 2 dose (RP2D) of niraparib with apalutamide or abiraterone acetate plus prednisone (AAP) in patients with metastatic castration-resistant prostate cancer (mCRPC).
A drug safety evaluation of abiraterone acetate in the treatment of prostate cancer. [2019]Introduction: To evaluate the safety profile characteristics of abiraterone acetate (AA) in the treatment of metastatic prostate cancer (mPCa). Areas covered: In this literature review the authors evaluate safety data from phase III trials investigating the combination of abiraterone acetate plus prednisone (AAP) in patients with metastatic prostate cancer. In particular, the aim was to clarify its toxicity profile, long-term exposure impact, and the correlation with general health-related quality of life (HRQoL). Expert opinion: Based on the studies reviewed, it appears that abiraterone acetate has favourable outcomes, is effective and well tolerated, mostly in asymptomatic or slightly symptomatic patients, and has recognised toxicity profile characteristics. Incidence of adverse events (AEs), such as mineralocorticoid- and corticosteroid-releated AEs, and hepatotoxicity is well known and widely described. Understanding the toxicity profile of AA could assist decision-making in clinical practice.
Niraparib with Abiraterone Acetate and Prednisone for Metastatic Castration-Resistant Prostate Cancer: Phase II QUEST Study Results. [2023]Niraparib (NIRA) is a highly selective inhibitor of poly (adenosine diphosphate-ribose) polymerase, PARP1 and PARP2, which play a role in DNA repair. The phase II QUEST study evaluated NIRA combinations in patients with metastatic castration-resistant prostate cancer who were positive for homologous recombination repair gene alterations and had progressed on 1 prior line of novel androgen receptor-targeted therapy. Results from the combination of NIRA with abiraterone acetate plus prednisone, which disrupts androgen axis signaling through inhibition of CYP17, showed promising efficacy and a manageable safety profile in this patient population.
Safety Profile of Ipatasertib Plus Abiraterone vs Placebo Plus Abiraterone in Metastatic Castration-resistant Prostate Cancer. [2023]Adding ipatasertib to abiraterone and prednisone/prednisolone significantly improved radiographic progression-free survival for patients with metastatic castration-resistant prostate cancer (mCRPC) with PTEN-loss tumours by immunohistochemistry in the IPATential150 trial (NCT03072238). Here we characterise the safety of these agents in subpopulations and assess manageability of key adverse events (AEs).
A phase II randomised trial of abiraterone acetate plus prednisone in combination with docetaxel or docetaxel plus prednisone after disease progression to abiraterone acetate plus prednisone in patients with metastatic castration-resistant prostate cancer: The ABIDO-SOGUG trial. [2022]We aimed to compare the efficacy and safety of maintaining or withdrawing abiraterone acetate plus prednisone (AAP) in patients with metastatic castration-resistant prostate cancer who had experienced cancer progression to this treatment and were beginning a docetaxel-based therapy.
The IMAAGEN Study: Effect of Abiraterone Acetate and Prednisone on Prostate Specific Antigen and Radiographic Disease Progression in Patients with Nonmetastatic Castration Resistant Prostate Cancer. [2021]We evaluated the use of abiraterone acetate (1,000 mg) plus prednisone (5 mg) in patients with high risk, nonmetastatic, castration resistant prostate cancer.
Abiraterone acetate and prednisone in chemotherapy-naïve prostate cancer patients: rationale, evidence and clinical utility. [2020]Abiraterone acetate 1000 mg/day, combined with prednisone 5 mg PO twice daily, is indicated for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Abiraterone acetate is the oral prodrug of abiraterone, a specific CYP17 inhibitor that blocks androgen biosynthesis within the adrenal glands, testes and tumor microenvironment. In a phase III trial of men with asymptomatic or minimally symptomatic, chemotherapy-naïve mCRPC, treatment with oral abiraterone acetate plus prednisone led to a statistically significant improvement in the co-primary endpoints of overall survival and radiographic progression-free survival when compared with placebo plus prednisone. In long-term follow-up of phase III trials, the incidence of corticosteroid-associated adverse events was 25.5% in the abiraterone acetate plus prednisone arm compared with 23.3% in the placebo plus prednisone arm. The need for regular patient monitoring and appropriate management of symptoms during long-term use of prednisone must be placed in context with the improvement in survival seen with abiraterone plus prednisone. Within the multidisciplinary environment that is emerging to meet quality and cost imperatives, abiraterone acetate plus prednisone is suitable for use in the chemotherapy-naïve population with minimal symptoms as well as in patients who have been treated with docetaxel and may have symptomatic disease. Ongoing trials are evaluating the role of abiraterone acetate plus prednisone in patients with nonmetastatic CRPC and metastatic hormone-sensitive prostate cancer, while further trials in the mCRPC setting are evaluating its use in combination regimens.
Assessment of the Safety of Glucocorticoid Regimens in Combination With Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer: A Randomized, Open-label Phase 2 Study. [2022]Abiraterone acetate is combined with prednisone, 5 mg, twice daily for metastatic castration-resistant prostate cancer (mCRPC) and with prednisone, 5 mg, once daily for newly diagnosed, high-risk, metastatic castration-sensitive prostate cancer. Understanding the physiological effects of these and other regimens is important.