Prostate CancerPhase 2KNIGHTSNCT06212583
High-Risk Metachronous Oligometastatic Prostate Cancer Trial
A Phase 2 study testing niraparib/abiraterone acetate, Stereotactic ablative radiation therapy (SABR) and Androgen deprivation therapy (ADT) in people with Prostate Cancer and Oligometastatic Disease, run by University of Maryland, Baltimore at 1 site in United States.
Trial summary
The purpose of this research study is to compare the effects, good and/or bad, of using the standard of care treatment, hormonal therapy + Stereotactic Ablative Radiation (SABR) to the metastatic lesions, compared to standard of care and addition of 6-months of niraparib/abiraterone acetate combination pills and… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer, Oligometastatic Disease
- What is being tested?
- niraparib/abiraterone acetate, Stereotactic ablative radiation therapy (SABR) and Androgen deprivation therapy (ADT)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Apr 2024to 31 Dec 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥18 years of age (or the local legal age of consent).
- Patient must have at least one and up to three asymptomatic metastatic tumor(s) of the bone, soft tissue, or extra-pelvic nodal region each < 5 cm or < 250 cm3 that develop within the past 6-months that are seen on imaging. A nodal lesion is defined to include nodal conglomerates located in the same nodal chain such that they can be treated in one SABR field. Up to five lesions are allowed on advanced functional imaging such as fluciclovine (Axumin), choline or Prostate Specific Membrane Antigen (PSMA) PET-CT scan.
- CT or MRI scan within 6 months of enrollment
- Bone scan within 6 months of enrollment
- Fluciclovine (Axumin), choline, or PSMA PET-CT scan within 6 months of enrollment (PET-CT scan is reasonable for study entry imaging as an alternative to CT/MRI scan and bone scan)
- Must have a high-risk pathogenic mutation (TP53, BRCA1/2, PALB2, ATM, BRIP1, CHEK2, FANCA, RAD51B, RAD54L, MUTYH) by next generation sequencing. ATM mutation enrollment will be capped at 5% of the overall population.
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- Histologic confirmation of prostate adenocarcinoma (primary or metastatic tumor).
- Patient may have had prior systemic therapy and/or ADT so long as testosterone is > 100 ng/dl prior to enrollment
- PSA > 0.5 but <50 at enrollment.
- Prostate Specific Antigen Doubling Time (PSADT) < 15 months
- Baseline testosterone > 100 ng/dl
- Patient must have a life expectancy ≥ 12 months.
- Patient must have an ECOG performance status ≤ 2.
- Adequate hematologic, renal, and hepatic function at screening defined as follows:
- Absolute neutrophil count ≥1.5 x 109/L
- Hemoglobin ≥9.0 g/dL, independent of transfusions for at least 28 days
- Platelet count ≥100 x 109/L
- Creatinine <2 x upper limit of normal (ULN)
- Serum potassium ≥3.5 mmol/L
- Serum total bilirubin ≤1.5× ULN or direct bilirubin ≤1 x ULN (Note: In participants with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin, and if direct bilirubin is ≤1.5 × ULN, participant may be eligible)
- AST or ALT ≤3 × ULN
- Patient must have the ability to understand and the willingness to sign a written informed consent document
- Able to swallow the study medication tablets whole.
- While on study medication and for 4 months following the last dose of study medication, a male participant must agree to use condom and an adequate contraception method for female partner (WOCBP) A male participant must agree not to donate sperm while on study treatment and for a minimum of 4 months following the last dose of study medication.
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- Castration-resistant prostate cancer (CRPC).
- Prior radiation therapy to an overlapping site of a target lesion that would preclude further radiation therapy
- Spinal cord compression or impending spinal cord compression.
- Suspected intracranial and/or liver metastases (>10 mm in largest axis).
- Patient receiving any other investigational agents.
- Inability to receive any form of systemic therapy in the opinion of a treating medical oncologist.
- Unable to lie flat during or tolerate PET/MRI, PET/CT or SABR.
- Radiographical evidence of cranial parenchymal metastasis.
- Active second primary malignancy; AML/MDS in medical history.
- Uncontrolled hypertension and myocardial infarction/PE/cardiac failure in last 6 months.
- Prior treatment with PARP inhibitor
- Refusal to sign informed consent.
- Pathological finding consistent with small cell or neuroendocrine carcinoma of the prostate.
- History of adrenal dysfunction
- Long-term use of systemically administered corticosteroids (>5mg of prednisone or the equivalent) during the study is not allowed. Short-term use (≤4 weeks, including taper) and locally administered steroids (eg, inhaled, topical, ophthalmic, and intra-articular) are allowed, if clinically indicated.
- 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.
- History or current diagnosis of MDS/AML.
- Current evidence within 6 months prior to randomization 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.
- Presence of sustained uncontrolled hypertension (systolic blood pressure >160 mm Hg or diastolic blood pressure >100 mm Hg). Participants with a history of hypertension are allowed, provided that blood pressure is controlled to within these limits by an antihypertensive treatment.
- Known allergies, hypersensitivity, or intolerance to the excipients of niraparib/abiraterone acetate tablets
- Current evidence of any medical condition that would make prednisone use contraindicated.
- Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 30 days before the planned first dose of study medication.
- Participants who have had the following ≤28 days prior to randomization:
- A transfusion (platelets or red blood cells);
- Hematopoietic growth factors;
- Major surgery
- Human immunodeficiency virus positive participants 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
- Active or symptomatic viral hepatitis or chronic liver disease; encephalopathy, ascites or bleeding disorders secondary to hepatic dysfunction.
- Moderate or severe hepatic impairment (Class B and C per Child-Pugh classification system.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, 21201
About this study
Official title: A Randomized Trial of High-risK metachroNous oligometastatIc Prostate Cancer With hiGh-risk Mutations Treated witH meTastasiS Directed Therapy and Niraparib/Abiraterone Acetate and Prednisone (KNIGHTS)
The purpose of this research study is to compare the effects, good and/or bad, of using the standard of care treatment, hormonal therapy + Stereotactic Ablative Radiation (SABR) to the metastatic lesions, compared to standard of care and addition of 6-months of niraparib/abiraterone acetate combination pills and prednisone for participants with recurrent metastatic prostate cancer.
Read the detailed description
In this trial all participants will be randomized to one of the two groups. You will be randomly assigned (by chance, like the flip of a coin) to one of the two groups: 1: Standard of care treatment (hormonal therapy + SABR to the metastatic lesions) or 2: Standard of care treatment + 6-months of niraparib/abiraterone acetate combination pills and prednisone. Participants in both groups will receive rectal swabs and various blood tests to assess circulating tumor cells, genomic sequencing, and tumor markers. Both groups will also participate in quality-of-life surveys
- Conditions
- Prostate Cancer, Oligometastatic Disease
- Being tested
- niraparib/abiraterone acetate, Stereotactic ablative radiation therapy (SABR), Androgen deprivation therapy (ADT)
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
niraparib/abiraterone acetateDrug
Patients on Arm 2 to receive drug for 6 months
Stereotactic ablative radiation therapy (SABR)Radiation
Both arms will receive SABR
Androgen deprivation therapy (ADT)Drug
All ADT is provided as best prescribed for patient per their medical oncologist.
| Study group | Role | What they receive |
|---|---|---|
| Androgen deprivation therapy + Stereotactic ablative radiation | Active comparator | Not described Receives: Radiation: Stereotactic ablative radiation therapy (SABR); Drug: Androgen deprivation therapy (ADT) |
| Androgen deprivation therapy + Stereotactic ablative radiation + niraparib/abiraterone acetate | Active comparator | Not described Receives: Drug: niraparib/abiraterone acetate; Radiation: Stereotactic ablative radiation therapy (SABR); Drug: Androgen deprivation therapy (ADT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
PSA (Prostate Specific Antigen) evaluation at the 18-month progression of both treatment arms
PSA evaluation of progression at 18-month PSA , defined as PSA > 0.2 ng/mL in patients initially treated with radical prostatectomy and greater than nadir + 2 ng/mL for patients initially treated with definitive radiation, with testosterone >100 ng/dl of men who have oligometastatic castration-sensitive prostate cancer with high-risk mutations (TP53, BRCA1/2, PALB2, ATM, BRIP1, CHEK2, FANCA, RAD51B, RAD54L, MUTYH) treated with ADT + SABR MDT (6-mos) versus ADT + SABR MDT + niraparib/abiraterone acetate and prednisone (6-mos).
Measured: 18 months
Secondary outcomes (4)
Treatment-related adverse events of both treatment arms
Number of participants with treatment-related adverse events from ADT+ SABR MDT (6-mos) vs ADT + SABR MDT + niraparib/abiraterone acetate and prednisone (6-mos) in patients with metachronous oligometastatic CSPC disease.
Measured: 4 years
Local control at 18 months after ADT+ SABR MDT (6-mos) vs ADT + SABR MDT + niraparib/abiraterone acetate and prednisone (6-mos) in patients with metachronous oligometastatic Castrate Specific Prostate Cancer (CSPC) disease.
Local control will be evaluated through clinical assessment and periodic imaging.
Measured: 18 months
Time to locoregional progression, time to distant progression, time to new metastasis, radiographic progression-free survival and duration of response after randomization
Progression will be assessed for time to locoregional progression, time to distant progression, time to new metastasis, radiographic progression-free survival and duration of response after randomization.
Measured: 4 years
Quality-of-life measured through EPIC tool following completion of ADT+ SABR MDT (6-mos) vs ADT + SABR MDT + niraparib/abiraterone acetate and prednisone (6-mos).
EPIC quality of life tool will be used to assess quality of life following treatment. Averages will be taken for each section in the survey (Urinary Function, Bowel Function, Sexual Function, and Hormonal function).
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2024
- Study start17 Apr 2024
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 88 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen Scientific Affairs, LLC
- Responsible party
- Principal investigator, Jason Molitoris, MD PhD, University of Maryland, Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06212583
- Sponsor's protocol ID
- HP-00108148
- Other IDs
- GCC 23100
- Acronym
- KNIGHTS
- Status last verified
- May 2026
- First submitted
- 14 Dec 2023
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial of High-risK metachroNous oligometastatIc Prostate Cancer With hiGh-risk Mutations Treated witH meTastasiS Directed Therapy and Niraparib/Abiraterone Acetate and Prednisone (KNIGHTS)
- ClinicalTrials.gov ID
- NCT06212583
- Acronym / sponsor ID
- KNIGHTS / HP-00108148
- Conditions
- Prostate Cancer, Oligometastatic Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 88 participants (estimated)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Collaborators
- Janssen Scientific Affairs, LLC
- Study start
- 17 Apr 2024 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 19 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to compare the effects, good and/or bad, of using the standard of care treatment, hormonal therapy + Stereotactic Ablative Radiation (SABR) to the metastatic lesions, compared to standard of care and addition of 6-months of niraparib/abiraterone acetate combination pills and prednisone for participants with recurrent metastatic prostate cancer.
Detailed description
In this trial all participants will be randomized to one of the two groups. You will be randomly assigned (by chance, like the flip of a coin) to one of the two groups: 1: Standard of care treatment (hormonal therapy + SABR to the metastatic lesions) or 2: Standard of care treatment + 6-months of niraparib/abiraterone acetate combination pills and prednisone. Participants in both groups will receive rectal swabs and various blood tests to assess circulating tumor cells, genomic sequencing, and tumor markers. Both groups will also participate in quality-of-life surveys
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Androgen deprivation therapy + Stereotactic ablative radiation | Active comparator | Radiation: Stereotactic ablative radiation therapy (SABR), Drug: Androgen deprivation therapy (ADT) |
| Androgen deprivation therapy + Stereotactic ablative radiation + niraparib/abiraterone acetate | Active comparator | Drug: niraparib/abiraterone acetate, Radiation: Stereotactic ablative radiation therapy (SABR), Drug: Androgen deprivation therapy (ADT) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (64 listed)
- ≥18 years of age (or the local legal age of consent).
- Patient must have at least one and up to three asymptomatic metastatic tumor(s) of the bone, soft tissue, or extra-pelvic nodal region each < 5 cm or < 250 cm3 that develop within the past 6-months that are seen on imaging. A nodal lesion is defined to include nodal conglomerates located in the same nodal chain such that they can be treated in one SABR field. Up to five lesions are allowed on advanced functional imaging such as fluciclovine (Axumin), choline or Prostate Specific Membrane Antigen (PSMA) PET-CT scan.
- Must have a high-risk pathogenic mutation (TP53, BRCA1/2, PALB2, ATM, BRIP1, CHEK2, FANCA, RAD51B, RAD54L, MUTYH) by next generation sequencing. ATM mutation enrollment will be capped at 5% of the overall population.
- Histologic confirmation of prostate adenocarcinoma (primary or metastatic tumor).
- Patient may have had prior systemic therapy and/or ADT so long as testosterone is > 100 ng/dl prior to enrollment
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| niraparib/abiraterone acetatePatients on Arm 2 to receive drug for 6 months | Drug | Androgen deprivation therapy + Stereotactic ablative radiation + niraparib/abiraterone acetate |
| Stereotactic ablative radiation therapy (SABR)Both arms will receive SABR | Radiation | Androgen deprivation therapy + Stereotactic ablative radiation, Androgen deprivation therapy + Stereotactic ablative radiation + niraparib/abiraterone acetate |
| Androgen deprivation therapy (ADT)All ADT is provided as best prescribed for patient per their medical oncologist. | Drug | Androgen deprivation therapy + Stereotactic ablative radiation, Androgen deprivation therapy + Stereotactic ablative radiation + niraparib/abiraterone acetate |
Primary outcome
PSA (Prostate Specific Antigen) evaluation at the 18-month progression of both treatment arms
Time frame: 18 months
PSA evaluation of progression at 18-month PSA , defined as PSA > 0.2 ng/mL in patients initially treated with radical prostatectomy and greater than nadir + 2 ng/mL for patients initially treated with definitive radiation, with testosterone >100 ng/dl of men who have oligometastatic castration-sensitive prostate cancer with high-risk mutations (TP53, BRCA1/2, PALB2, ATM, BRIP1, CHEK2, FANCA, RAD51B, RAD54L, MUTYH) treated with ADT + SABR MDT (6-mos) versus ADT + SABR MDT + niraparib/abiraterone acetate and prednisone (6-mos).
4 secondary outcomes
Treatment-related adverse events of both treatment arms
Time frame: 4 years
Local control at 18 months after ADT+ SABR MDT (6-mos) vs ADT + SABR MDT + niraparib/abiraterone acetate and prednisone (6-mos) in patients with metachronous oligometastatic Castrate Specific Prostate Cancer (CSPC) disease.
Time frame: 18 months
Time to locoregional progression, time to distant progression, time to new metastasis, radiographic progression-free survival and duration of response after randomization
Time frame: 4 years
Quality-of-life measured through EPIC tool following completion of ADT+ SABR MDT (6-mos) vs ADT + SABR MDT + niraparib/abiraterone acetate and prednisone (6-mos).
Time frame: 4 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing niraparib/abiraterone acetate, Stereotactic ablative radiation therapy (SABR) and Androgen deprivation therapy (ADT) in people with Prostate Cancer and Oligometastatic Disease, run by University of Maryland, Baltimore at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 64 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PSA (Prostate Specific Antigen) evaluation at the 18-month progression of both treatment arms (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2026.