Trial Outcomes & Findings for Testing the Addition of a New Anti-Cancer Drug, Niraparib, to the Usual Treatment (Hormone and Radiation Therapy) for Prostate Cancer With a High Chance of Recurring (NCT NCT04037254)

Last Updated: 2025-07-28

Results Overview

Participants will be considered disease-free if their PSA values remain below 0.1 ng/ml until the completion of treatment. The proportion of patients disease-free at 24 months were to be compared in the two treatment arms using a non-continuity-corrected chi-square test. PSA levels will be assessed prior to the start of RT, at the end of RT, and every three months for 24 months. all PSA values obtained up to and including the two-year landmark must be \< 0.1 ng/ml. Patients who die prior to two years from prostate cancer will be counted as failures. Patients who die from causes other than prostate cancer will be considered non-evaluable for the primary endpoint. Patients still under follow-up but who have a missing PSA value at two years or more than two missing values prior to two years will also be counted as failures.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE1/PHASE2

Target enrollment

22 participants

Primary outcome timeframe

Baseline to completion of treatment (two years from start of ADT)

Results posted on

2025-07-28

Participant Flow

Participant milestones

Participant milestones
Measure	Phase I, Dose Level 1 (DL1) (Niraparib, GnRH, IMRT) Patients undergo standard of care gonadotrophin releasing hormone (GnRH) agonist androgen suppression therapy for 24 months, and niraparib PO QD\* for 12 months in the absence of disease progression or unacceptable toxicity. Beginning 8 weeks after starting niraparib, patients undergo standard of care intensity-modulated radiation therapy (IMRT) 5 days per week for about 6-9 weeks depending on type of radiation therapy given in the absence of disease progression or unacceptable toxicity. \*niraparib dose level 1: 100 mg.	Phase I, Dose Level 2 (DL2) (Niraparib, GnRH, IMRT) Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months, and niraparib PO QD\* for 12 months in the absence of disease progression or unacceptable toxicity. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy given in the absence of disease progression or unacceptable toxicity. \*niraparib dose level 2: 100 mg during IMRT 200 mg all other time.	Phase I, Dose Level 3 (DL3) (Niraparib, GnRH, IMRT) Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months, and niraparib PO QD\* for 12 months in the absence of disease progression or unacceptable toxicity. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy given in the absence of disease progression or unacceptable toxicity. \*niraparib dose level 3: 200 mg.
Overall Study STARTED	7	7	8
Overall Study Eligible and Evaluable	6	5	6
Overall Study COMPLETED	6	5	6
Overall Study NOT COMPLETED	1	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I, Dose Level 1 (DL1) (Niraparib, GnRH, IMRT) Patients undergo standard of care gonadotrophin releasing hormone (GnRH) agonist androgen suppression therapy for 24 months, and niraparib PO QD\* for 12 months in the absence of disease progression or unacceptable toxicity. Beginning 8 weeks after starting niraparib, patients undergo standard of care intensity-modulated radiation therapy (IMRT) 5 days per week for about 6-9 weeks depending on type of radiation therapy given in the absence of disease progression or unacceptable toxicity. \*niraparib dose level 1: 100 mg.	Phase I, Dose Level 2 (DL2) (Niraparib, GnRH, IMRT) Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months, and niraparib PO QD\* for 12 months in the absence of disease progression or unacceptable toxicity. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy given in the absence of disease progression or unacceptable toxicity. \*niraparib dose level 2: 100 mg during IMRT 200 mg all other time.	Phase I, Dose Level 3 (DL3) (Niraparib, GnRH, IMRT) Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months, and niraparib PO QD\* for 12 months in the absence of disease progression or unacceptable toxicity. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy given in the absence of disease progression or unacceptable toxicity. \*niraparib dose level 3: 200 mg.
Overall Study Protocol Violation	1	0	0
Overall Study Withdrawal by Subject	0	0	1
Overall Study Delayed or incomplete treatment	0	2	1

Baseline Characteristics

Testing the Addition of a New Anti-Cancer Drug, Niraparib, to the Usual Treatment (Hormone and Radiation Therapy) for Prostate Cancer With a High Chance of Recurring

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Baseline to completion of treatment (two years from start of ADT)

Population: Eligible and evaluable phase II participants followed for two years after start of ADT. The study did/will not advance to the phase II component.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From baseline to death or last follow-up, analyzed after phase II participants have been followed for two years, which was expected to occur 3.5 years from start of phase II component.

Population: Eligible phase II participants. The study did/will not advance to the phase II component.

Survival rates were to be estimated using the Kaplan-Meier method and the treatment arms were to be compared using a log-rank test.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From baseline to death or last follow-up, analyzed after all phase II participants have been followed for two years, which was expected to occur 3.5 years from start of phase II component.

Population: Eligible phase II participants. The study did/will not advance to the phase II component.

Prostate cancer death rates were to be estimated using the cumulative incidence method, treating deaths due to other causes as competing risks. The treatment arms were to be compared using the Fine-Gray test

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At two years

Population: Eligible phase II participants with 12-core biopsy at 24 months. The study did/will not advance to the phase II component.

Complete response was to be determined by a12-core biopsy. Treatment arms were to be compared using a chi-square test.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From baseline to local/regional or distant progression, death, or last follow-up, whichever occurs first, analyzed after all phase II participants have been followed for two years, which was expected to occur 3.5 years from start of phase II component.

Population: Eligible phase II participants. The study did/will not advance to the phase II component.

Progression rates were to be estimated using the cumulative incidence method, treating deaths as competing risks. The treatment arms were to be compared using the Fine-Gray test

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From baseline to distant metastasis, death, or last follow-up, analyzed after all phase II participants have been followed for two years, which was expected to occur 3.5 years from start of phase II component.

Population: Eligible phase II participants. The study did not and will not advance to the phase II component.

Distant metastases rates were to be estimated using the cumulative incidence method, treating death as a competing risk. The treatment arms were to be compared using the Fine-Gray test

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From baseline to biochemical progression or last follow-up, analyzed after all phase II participants have been followed for two years, which was expected to occur 3.5 years from start of phase II component.

Population: Eligible phase II participants. The study did/will not advance to the phase II component.

Biochemical progression is defined as PSA ≥ 2 ng/ml over the nadir PSA, the presence of local, regional, or distant recurrence, or death from prostate cancer. Biochemical progression-free survival rates were to be estimated using the Kaplan-Meier method and the treatment arms were to be compared using a log-rank test.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From baseline to last follow-up, analyzed after all phase II participants have been followed for two years, which was expected to occur 3.5 years from start of phase II component.

Population: Eligible phase II participants. The study did not and will not advance to the phase II component.

Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data. Adverse events were to be categorized as early (within 90 days of completion of radiotherapy) or late (more than 90 days after the completion of radiotherapy).The number of participants per grade was to be compared between the arms for early, late, and all adverse events using chi-square or Fisher exact tests

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From start of combined ADT and niraparib to six months

Population: Eligible and evaluable phase I participants.

MTD was determined using the classic 3+3 design to determine the safety of each dose level (DL) from the number of participants with dose limiting toxicities (DLTs), starting with DL1. The highest DL deemed safe was to be considered the MTD. The timing of the 3-patient cohorts took into account the previously established safety of concurrent ADT and 200 mg niraparib and the need to more clearly establish the safety of niraparib concurrent with RT. A DLT is defined as any treatment-related gastrointestinal or genitourinary grade 3 or higher AE lasting \> 1 week, despite maximal medical interventions, and any treatment-related grade 4 AEs lasting \> 1 week. Relationship to treatment was determined by the responsible clinician. Study chairs reviewed possible DLTs for final determination. Niraparib dose level (mg PO QD) definitions \[First 8 weeks with ADT, 6-8 weeks with ADT and RT, remaining time of the 12 months\]: * DL1: 100, 100, 100 * DL2: 200, 100, 200 * DL3: 200, 200, 200

Outcome measures

Outcome measures
Measure	Phase II, Arm I (GnRH, IMRT) n=17 Participants Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months in the absence of disease progression or unacceptable toxicity. Beginning 8-28 weeks after starting GnRH agonist, patients undergo IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy given in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI on study.	Phase II, Arm II (Niraparib, GnRH, IMRT) Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months, and niraparib PO QD (phase I determined dose level) for 12 months in the absence of disease progression or unacceptable toxicity. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy given in the absence of disease progression or unacceptable toxicity.	Phase I, Dose Level 3 (Niraparib, GnRH, IMRT) Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months, and niraparib PO QD\* for 12 months in the absence of disease progression or unacceptable toxicity. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy given in the absence of disease progression or unacceptable toxicity. \*niraparib dose level 3: 200 mg.
Maximum Tolerated Dose (MTD) of Niraparib/ Preferred Niraparib Dose for Phase II Component	3 Dose level	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: From start of combined ADT and niraparib to six months

Population: Eligible and evaluable phase I participants.

A DLT is defined as any treatment-related gastrointestinal or genitourinary grade 3 or higher AE lasting \> 1 week, despite maximal medical interventions, and any treatment-related grade 4 AEs lasting \> 1 week. Relationship to treatment was determined by the responsible clinician. Study chairs reviewed possible DLTs for final determination.

Outcome measures

Outcome measures
Measure	Phase II, Arm I (GnRH, IMRT) n=6 Participants Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months in the absence of disease progression or unacceptable toxicity. Beginning 8-28 weeks after starting GnRH agonist, patients undergo IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy given in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI on study.	Phase II, Arm II (Niraparib, GnRH, IMRT) n=5 Participants Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months, and niraparib PO QD (phase I determined dose level) for 12 months in the absence of disease progression or unacceptable toxicity. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy given in the absence of disease progression or unacceptable toxicity.	Phase I, Dose Level 3 (Niraparib, GnRH, IMRT) n=6 Participants Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months, and niraparib PO QD\* for 12 months in the absence of disease progression or unacceptable toxicity. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy given in the absence of disease progression or unacceptable toxicity. \*niraparib dose level 3: 200 mg.
Number of Participants Who Experienced Dose-limiting Toxicities (DLT)	0 Participants	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to death or last follow-up, analyzed after all participants have been followed for two years and gene mutation data produced

Population: Eligible phase II participants with gene alteration data. The study did not and will not advance to the phase II component.

The percentage of patients with baseline or post-therapy alterations in targeted genes would be reported and the association between the occurrence of alterations and clinical outcomes would be assessed.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to death or last follow-up, analyzed after all participants have been followed for two years and gene expression data generated.

Population: Eligible phase II participants with gene expression data. The study did not and will not advance to the phase II component.

The percentage of participants with baseline or post-therapy gene expression and the association between the occurrence of alterations and clinical outcomes would be assessed.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to death or last follow-up, analyzed after all participants have been followed for two years and polymorphism data generated.

Population: Eligible phase II participants with polymorphism data. The study did not and will not advance to the phase II component.

The percentage of patients with baseline or post-therapy polymorphism would be reported and the association between the occurrence of alterations and clinical outcomes would be assessed.

Outcome measures

Outcome data not reported

Adverse Events

Phase I, Dose Level 1 (Niraparib, GnRH, IMRT)

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Phase I, Dose Level 2 (Niraparib, GnRH, IMRT)

Serious events: 3 serious events

Other events: 5 other events

Deaths: 0 deaths

Phase I, Dose Level 3 (Niraparib, GnRH, IMRT)

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Wendy Seiferheld

NRG Oncology

Phone: 215-574-3208

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
Publication restrictions are in place

Restriction type: OTHER

Measure	Phase I, Dose Level 1 (Niraparib, GnRH, IMRT) n=6 Participants Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months and concurrent niraparib PO QD\* for the first 12 months. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy. Treatment is given in the absence of disease progression or unacceptable toxicity. \*niraparib dose level 1: 100 mg.	Phase I, Dose Level 2 (Niraparib, GnRH, IMRT) n=5 Participants Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months and concurrent niraparib PO QD\* for the first 12 months. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy. Treatment is given in the absence of disease progression or unacceptable toxicity. \*niraparib dose level 2: 100 mg during IMRT 200 mg otherwise.	Phase I, Dose Level 3 (Niraparib, GnRH, IMRT) n=6 Participants Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months and concurrent niraparib PO QD\* for the first 12 months. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy. Treatment given in the absence of disease progression or unacceptable toxicity. \*niraparib dose level 3: 200 mg.	Total n=17 Participants Total of all reporting groups
Age, Continuous	72.5 years n=5 Participants	74 years n=7 Participants	71 years n=5 Participants	72 years n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	17 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	17 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	15 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
T-Stage T1	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
T-Stage T2	6 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	11 Participants n=4 Participants
T-Stage T3	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
T-Stage T4	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
N-Stage N0	6 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	17 Participants n=4 Participants
N-Stage N1	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Gleason score 9	5 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	16 Participants n=4 Participants
Gleason score 10	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Baseline Prostate-specific antigen (PSA) PSA < 20 ng/mL	5 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	16 Participants n=4 Participants
Baseline Prostate-specific antigen (PSA) PSA ≥ 20-150 ng/mL	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants