Androgen Ablation Therapy With or Without Niraparib After Radiation Therapy for the Treatment of High-Risk Localized or Locally Advanced Prostate Cancer

NCT04947254 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2020-1039NCI-2021-05724
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the effect of androgen ablation therapy with or without niraparib after standard of care radiation therapy in treating patients with prostate cancer that has not spread to other parts of the body (localized) or that has spread to nearby tissue or lymph nodes (locally advanced). Androgen ablation therapy (also known as hormone therapy) lowers the levels of male hormones called androgens in the body. Androgens stimulate prostate cancer cells to grow. There are 2 types of androgen ablation therapy given in this study: AAP + ADT and Apa + ADT. AAP + ADT is the treatment combination of the drugs abiraterone acetate and prednisone (AAP) given with androgen deprivation therapy (ADT, also known as androgen deprivation therapy or androgen suppression medication, which is used as standard of care to lower testosterone levels in men with high risk localized or metastatic prostate cancer). Apa + ADT is the treatment combination of the drug apalutamide (Apa) given with ADT. Androgen ablation therapy with or without niraparib after radiation therapy may help to control the disease in patients with prostate cancer.

Conditions

Stage IIC Prostate Cancer AJCC v8; Prostate Carcinoma; Stage III Prostate Cancer AJCC v8; Stage IIIA Prostate Cancer AJCC v8; Stage IIIB Prostate Cancer AJCC v8; Stage IIIC Prostate Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Composite radiographic progression-free survival(rPFS) and biochemical (PSA) progression-free survival (PFS)

  From randomization until progression, death, or last assessment without progression, whichever comes first, assessed at 3 years

Secondary Outcomes (5)

• Incidence and severity of adverse events (AEs)

  Up to 3 years

• Incidence and severity of serious adverse events (SAEs)

  Up to 3 years

• Overall survival

  From randomization until death or last contact, whichever comes first, assessed up to 3 years

• Eugonadal progression-free survival

  From randomization until progression, death, or last assessment without progression, whichever comes first, assessed up to 3 years

• Progression-free survival

  From randomization until progression, death, or last assessment without progression, whichever comes first, assessed up to 3 years

Study Arms (2)

Group A (Apa, ADT, XRT)

ACTIVE COMPARATOR

PART 1 NEOADJUVANT PHASE (CYCLES 1-3): Patients receive PO QD on days 1-28, and physician's choice ADT. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. PART 2 RADIATION PHASE (CYCLES 4-6): Within 30 days of completing Part 1, patients undergo radiation therapy. Patients also receive apalutamide PO QD on days 1-28 and physician's choice ADT. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. PART 3 ADJUVANT PHASE (CYCLES 7 AND BEYOND): Patients receive apalutamide PO QD on days 1-28 and physician's choice ADT. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Antiandrogen Therapy; Drug: Apalutamide; Procedure: Biopsy; Radiation: Radiation Therapy

Group B (Apa, ADT, XRT, AAP, niraparib)

EXPERIMENTAL

PART 1 NEOADJUVANT PHASE (CYCLES 1-3): Patients receive PO QD on days 1-28, and physician's choice ADT. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. PART 2 RADIATION PHASE (CYCLES 4-6): Within 30 days of completing Part 1, patients undergo radiation therapy. Patients also receive apalutamide PO QD on days 1-28 and physician's choice ADT. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. PART 3 ADJUVANT PHASE (CYCLES 7 AND BEYOND): Patients receive abiraterone acetate PO QD, prednisone PO BID, physician's choice ADT, and niraparib PO QD. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Abiraterone Acetate; Drug: Antiandrogen Therapy; Drug: Apalutamide; Procedure: Biopsy; Drug: Niraparib; Drug: Prednisone; Radiation: Radiation Therapy

Interventions

Abiraterone Acetate DRUG

Given PO

Also known as: CB7630, Zytiga

Group B (Apa, ADT, XRT, AAP, niraparib)

Antiandrogen Therapy DRUG

Given ADT

Also known as: ADT, Androgen Deprivation Therapy, Androgen Deprivation Therapy (ADT), Anti-androgen Therapy, Anti-androgen Treatment, Antiandrogen Treatment, Hormone Deprivation Therapy, Hormone-Deprivation Therapy

Group A (Apa, ADT, XRT); Group B (Apa, ADT, XRT, AAP, niraparib)

Apalutamide DRUG

Given PO

Also known as: ARN 509, ARN-509, ARN509, Erleada, JNJ 56021927, JNJ-56021927

Group A (Apa, ADT, XRT); Group B (Apa, ADT, XRT, AAP, niraparib)

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Group A (Apa, ADT, XRT); Group B (Apa, ADT, XRT, AAP, niraparib)

Niraparib DRUG

Given PO

Also known as: MK-4827, MK4827

Group B (Apa, ADT, XRT, AAP, niraparib)

Prednisone DRUG

Given PO

Also known as: .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, Perrigo Prednisone, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisone Intensol, Prednisonum, Prednitone, Promifen, Rayos, Servisone, SK-Prednisone

Group B (Apa, ADT, XRT, AAP, niraparib)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Group A (Apa, ADT, XRT); Group B (Apa, ADT, XRT, AAP, niraparib)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Completion of informed consent prior to any study specific procedures. Consent may be done remotely.
• Patients must agree to tissue collection for correlative studies at the specified timepoints
• Male aged 18 years and above
• Histologically or cytologically confirmed prostate carcinoma
• Localized or regional high-risk disease as defined by at least one of the following features: Prostate specific antigen (PSA) \> 20 ng/mL, T3a or higher, grade group 4-5 (i.e. Gleason score ≥ 8) as per National Comprehensive Cancer Network (NCCN) Prostate Cancer Version 2.2020 for high risk or very high risk prostate cancer, and/or regional lymph nodes positive for prostate cancer
• Planned for definitive treatment of local regional prostate cancer using XRT and androgen ablation
• Willing to undergo ongoing medical castration to maintain testosterone levels of ≤ 50 ng/dL (≤ 2.0 nM) throughout systemic treatment or have undergone bilateral orchiectomy
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. Patients must have adequate organ and bone marrow function measured within 7 days prior to treatment registration as defined below:
• Hemoglobin ≥ 10.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
• White blood cells (WBC) \> 3 x 10\^9/L
• No features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) on peripheral blood smear
• Platelet count ≥ 100 x 10\^9/L
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (except for patients with known Gilbert's disease). (Note: In subjects with Gilbert's syndrome, if total bilirubin is \> 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1.5 x ULN, subject may be eligible.)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 x institutional upper limit of normal

You may not qualify if:

• Any prior systemic treatment for prostate cancer with the exception of ADT started within 6 months of trial enrollment. Any prior PARP inhibitor therapy
• Patients who have prostate cancer with distant metastatic disease
• Patients who have had prior major surgery (prostatectomy) or radiotherapy for the treatment of prostate cancer
• Any unresolved toxicity (Common Terminology Criteria for Adverse Events \[CTCAE\] grade ≥ 2) from previous anti-cancer therapies
• History or current diagnosis of MDS/AML, and/or history of any malignancy \[other than the one treated in this study\] which has a ≥ 30% probability of recurrence within 24 months (except for adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix or Ta urothelial carcinomas)
• Active uncontrolled infection (patients completing a course of antibiotic or antiviral therapy whose infection is deemed to be controlled may be allowed on study after discussion with the principal investigator \[PI\]; the PI will serve as the final arbiter regarding eligibility)
• Active or symptomatic viral hepatitis or chronic liver disease
• Active pneumonitis or extensive bilateral lung disease of non-malignant etiology
• Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events. Examples include, but are not limited to superior vena cava syndrome, extensive bilateral lung disease on high resolution computed tomography (HRCT) scan, uncontrolled seizures, history of allogeneic organ transplant, history of primary immunodeficiency or any psychiatric disorder that prohibits obtaining informed consent
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of study medication
• Patients with a known hypersensitivity to niraparib, apalutamide, and/or abiraterone acetate
• Prisoners or subjects who are involuntarily incarcerated
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness
• Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system \[CNS\] or meningeal disease which may require treatment with surgery or radiation therapy)
• Severe or unstable angina, myocardial infarction (within 6 months prior to enrollment), symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), uncontrolled hypertension, or clinically significant ventricular arrhythmias within 6 months prior to randomization

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Abiraterone Acetate; Androgen Antagonists; apalutamide; Biopsy; niraparib; Prednisone; deltacortene; prednylidene; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Pregnadienediols; Pregnadienes; Pregnanes; Therapeutics; Physical Phenomena

Study Officials

• Patrick G Pilie

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2021
• First Posted: July 1, 2021
• Study Start: August 5, 2021
• Primary Completion (Estimated): June 7, 2026
• Study Completion (Estimated): June 7, 2026
• Last Updated: February 19, 2026

Record last verified: 2026-02

Locations

US (1)