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Trial · Interventional

CompletedPhase 1/2Results postedRegistry data

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

NCTNCT04037254 (opens ClinicalTrials.gov in a new tab)Other idNRG-GU007Other idNCI-2019-02260Other idNRG-GU007Other idNRG-GU007

Overview

Status
Completed
Phase
Phase 1/2
Enrollment
22 participants (actual)
Sponsor
NRG Oncology · Other
Design
Randomized · Open label (no masking)
Countries
2 countries

United States, Canada

Start
8 Oct 2019
Primary completion
1 Jul 2024
Completion
23 Dec 2025
First posted
30 Jul 2019
Last update posted
10 Jul 2026
Conditions
Prostate Adenocarcinoma · Stage IIC Prostate Cancer AJCC v8 · 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

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2020202220242026
  1. Ph 1/2

    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

    NCT04037254

    8 Oct 2019 to 23 Dec 2025

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

This is a phase I-II trial to find the safety and activity of adding a new drug (neraparib) to the usual treatment (radiation combined with male hormone deprivation therapy) in lowering the chance of prostate cancer growing or returning. Niraparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Adding niraparib to the usual care may lower the chance of prostate cancer growing or returning.

Interventions

  • Gonadotrophin Releasing HormoneBiological
  • Intensity-Modulated Radiation TherapyRadiation
  • NiraparibDrug

Arms5

  • Experimental

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

    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.

  • Experimental

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

    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.

  • Experimental

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

    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.

  • Active comparator

    Phase II, Arm I (GnRH, IMRT)

    Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months. 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. Treatment is given in the absence of disease progression or unacceptable toxicity.

  • Experimental

    Phase II, Arm II (niraparib, GnRH, IMRT)

    Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months and concurrent niraparib PO QD (phase I determined dose level) 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.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Number of Participants Disease-free Until Completion of Treatment (2 Years From Start of ADT)

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

    Registry description

    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.

Secondary outcomes(7)
  1. Percent of Participants Alive (Overall Survival)

    Time frame · 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.

    Registry description

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

  2. Percentage of Participants With Prostate Cancer Deaths (Prostate Cancer-specific Survival)

    Time frame · 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.

    Registry description

    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

  3. Percentage of Participants With Pathologic Complete Response (pCR) at Two Years

    Time frame · At two years

    Registry description

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

  4. Percentage of Participants With Local/Regional or Distant Progression

    Time frame · 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.

    Registry description

    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

  5. Percentage of Participants With Distant Metastases

    Time frame · 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.

    Registry description

    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

  6. Percentage of Participants Alive Without Biochemical Progression (Biochemical Progression-free Survival)

    Time frame · 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.

    Registry description

    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.

  7. Number of Participants by Highest Grade Adverse Event Reported

    Time frame · 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.

    Registry description

    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

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

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

Number of Participants Disease-free Until Completion of Treatment (2 Years From Start of ADT)

GroupValue
Phase II, Arm I (GnRH, IMRT)not posted
Phase II, Arm II (Niraparib, GnRH, IMRT)not posted
Secondary and other outcome results(7)
Secondary outcome· 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.

Percent of Participants Alive (Overall Survival)

GroupValue
Phase II, Arm I (GnRH, IMRT)not posted
Phase II, Arm II (Niraparib, GnRH, IMRT)not posted
Secondary outcome· 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.

Percentage of Participants With Prostate Cancer Deaths (Prostate Cancer-specific Survival)

GroupValue
Phase II, Arm I (GnRH, IMRT)not posted
Phase II, Arm II (Niraparib, GnRH, IMRT)not posted
Secondary outcome· At two years

Percentage of Participants With Pathologic Complete Response (pCR) at Two Years

GroupValue
Phase II, Arm I (GnRH, IMRT)not posted
Phase II, Arm II (Niraparib, GnRH, IMRT)not posted
Secondary outcome· 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.

Percentage of Participants With Local/Regional or Distant Progression

GroupValue
Phase II, Arm I (GnRH, IMRT)not posted
Phase II, Arm II (Niraparib, GnRH, IMRT)not posted
Secondary outcome· 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.

Percentage of Participants With Distant Metastases

GroupValue
Phase II, Arm I (GnRH, IMRT)not posted
Phase II, Arm II (Niraparib, GnRH, IMRT)not posted
Secondary outcome· 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.

Percentage of Participants Alive Without Biochemical Progression (Biochemical Progression-free Survival)

GroupValue
Phase II, Arm I (GnRH, IMRT)not posted
Phase II, Arm II (Niraparib, GnRH, IMRT)not posted
Secondary outcome· 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.

Number of Participants by Highest Grade Adverse Event Reported

GroupValue
Phase II, Arm I (GnRH, IMRT)not posted
Phase II, Arm II (Niraparib, GnRH, IMRT)not posted

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Phase I, Dose Level 1 (Niraparib, GnRH, IMRT)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.0 / 63 / 66 / 6
Phase I, Dose Level 2 (Niraparib, GnRH, IMRT)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.0 / 53 / 55 / 5
Phase I, Dose Level 3 (Niraparib, GnRH, IMRT)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.0 / 63 / 66 / 6

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
Male
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * Histologically confirmed (within 180 days prior to registration) adenocarcinoma of the prostate at high risk for recurrence as determined by the following criteria, according to American Joint Committee on Cancer (AJCC) 8th edition: * Phase I enrollment * Gleason \>= 9, PSA =\< 150 ng/mL, any T-stage * Phase II enrollment * Gleason \>= 9, PSA =\< 150 ng/mL, any T-stage * Gleason 8, PSA \< 20 ng/mL, and \>= T2 * Gleason 8, PSA \>= 20-150 ng/mL, any T-stage * Gleason 7, PSA \>= 20-150 ng/mL, any T-stage * No distant metastases as evaluated by: * Bone scan 90 days prior to registration * Lymph node assessment by computed tomography (CT) or magnetic resonance (MR) of pelvis or nodal sampling within 90 days prior to registration (Please note: Lymph nodes will be considered negative \[N0\] if they are \< 1.5 cm short axis) * History/physical examination within 90 days prior to registration * Age \>= 18 * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 180 days prior to registration * Pretreatment serum PSA, obtained prior to any androgen suppression therapy and within 180 days of registration * Phase I patients: Prior androgen suppression for prostate cancer is not allowed prior to registration * Phase II patients: Prior androgen suppression for prostate cancer is allowed =\< 45 days prior to registration * Hemoglobin \>= 9.0 g/dL (within 90 days prior to registration) * Platelets \>= 100,000 cells/mm\^3 (within 90 days prior to registration) * Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (within 90 days prior to registration) * Serum creatinine =\<1.5 x upper limit of normal (ULN) OR a calculated creatinine clearance \>= 30 mL/min estimated using Cockcroft-Gault equation (within 90 days prior to registration) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3.0 x ULN (within 90 days prior to registration) * Serum albumin \>= 3 g/dL (within 90 days prior to registration) * Serum potassium \>= 3.5 mmol/L (within 90 days prior to registration) * Serum total bilirubin =\< 1.5 x ULN or direct bilirubin =\< 1 x ULN (Note: in subjects with Gilberts 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) (within 90 days prior to registration) * Men of child-producing potential must be willing to consent to use effective contraception while on treatment and for at least 3 months afterwards * The patient or a legally authorized representative must provide study-specific informed consent prior to study entry Exclusion Criteria: * PSA \> 150 ng/mL * Definitive clinical or radiologic evidence of metastatic disease * Pathologically positive lymph nodes or nodes \> 1.5 cm short axis on CT or MR imaging * Prior radical prostatectomy, cryosurgery for prostate cancer, or bilateral orchiectomy for any reason * Any active malignancy within 2 years of study registration that may alter the course of prostate cancer treatment * Prior systemic therapy for prostate cancer; note that prior therapy for a different cancer is allowable * Prior radiotherapy, including brachytherapy, to the region of the prostate that would result in overlap of radiation therapy fields * Current treatment with first generation anti-androgens (bicalutamide, nilutamide, flutamide). For patients enrolled to phase II, if prior anti-androgens were administered, a washout period of \>= 30 days is required prior to enrollment * Severe, active co-morbidity, defined as follows: * Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months * Transmural myocardial infarction within the last 6 months * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration * Uncontrolled acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition * Presence of uncontrolled hypertension (persistent systolic blood pressure \[BP\] \>=160 mmHg or diastolic BP \>= 100 mmHg). Subjects with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment * Prior allergic reaction to the drugs involved in this protocol (including known allergies, hypersensitivity or intolerance to the excipients of niraparib) * Human immunodeficiency virus (HIV) positive with CD4 count \< 200 cells/microliter * Note that patients who are HIV positive are eligible, provided they have a CD4 count \>= 200 cells/microliter within 90 days prior to registration. Patients receiving treatment with highly active antiretroviral therapy (HAART) will not be eligible due to concern for radiosensitization * Note also that HIV testing is not required for eligibility for this protocol. This exclusion criterion is necessary because the treatments involved in this protocol may be affected by these drugs * Any history or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) * Prior or current treatment with PARP inhibitor

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