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A Trial of Niraparib in Platinum-Sensitive Castration-Resistant Prostate Cancer With DNA Repair Defects

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ClinicalTrials.gov Identifier: NCT04288687
Recruitment Status : Recruiting
First Posted : February 28, 2020
Last Update Posted : February 26, 2021
Sponsor:
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania

Brief Summary:
This study is designed to evaluate the initial safety and effectiveness of an investigational drug, niraparib, given to patients who have recently received platinum-based chemotherapy for the treatment of prostate cancer. The study enrolls participants with history of advanced prostate cancer that is growing despite standard hormonal therapies, such as androgen-deprivation therapy.

Condition or disease Intervention/treatment Phase
Prostate Adenocarcinoma Drug: Niraparib Pill Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: PLATPARP: A Phase II Single-Arm Trial of Niraparib in Platinum-Sensitive Castration-Resistant Prostate Cancer With DNA Repair Defects
Actual Study Start Date : October 19, 2020
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Niraparib Arm (only arm)
Niraparib 200 mg by mouth daily (2 x 100 mg pills) on a 28 day cycle
Drug: Niraparib Pill
Niraparib 200 mg by mouth daily (2 x 100 mg pills)




Primary Outcome Measures :
  1. rPFS6 [ Time Frame: 6 months ]
    Assessment of the 6-month radiographic progression-free survival (rPFS) rate in patients with platinum-sensitive mCRPC harboring germline or somatic DNA repair defects as determined by Kaplan-Meier analysis.


Secondary Outcome Measures :
  1. PSA30 [ Time Frame: 3 months ]
    Proportion of patients achieving a ≥30% decline in PSA following the initiation of niraparib maintenance therapy

  2. PSA50 [ Time Frame: 3 months ]
    Proportion of patients achieving a ≥50% decline in PSA following the initiation of niraparib maintenance therapy

  3. Time to PSA progression [ Time Frame: 6 months ]
    Time until the first PSA increase that is >25% (and an absolute increase of ≥ 2 ng/ml) from the nadir PSA value following the initiation of niraparib maintenance therapy

  4. Frequency and severity of adverse events (AEs) [ Time Frame: 1 month ]
    Frequency and severity of adverse events (AEs), as assessed by CTCAE version 5.0, following the initiation of niraparib maintenance therapy

  5. Overall survival (OS) [ Time Frame: 12 months ]
    Time from start of study therapy to death due to any cause. Patients who are alive will be censored on the most recent date of patient contact



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma (mixed histology will be acceptable, but pure small cell histology is to be excluded).
  2. ≥ 18 years of age.
  3. No prior therapy with PARP inhibitor therapy.
  4. Patients must have received at least 9 weeks of platinum-based chemotherapy for the treatment of mCRPC as the proximal treatment regimen prior to study screening. Patients must not have evidence of clinical or radiographic disease progression (per Investigator assessment) and should have adequately recovered from chemotherapy-related toxicities (at least 4 weeks following completion of chemotherapy, with treatment-related toxicities ≤ grade 1 per CTCAE version 5).
  5. ECOG performance status of ≤ 2.
  6. Documented evidence of a pathogenic or likely pathogenic DNA repair aberration in BRCA1/2, ATM, FANCA, PALB2, CHEK2, HDAC2, or BRIP1 through either somatic or germline testing from a CLIA certified laboratory.
  7. Radiographic evidence for metastatic disease. Measureable disease (per RECIST) is not required for enrollment. (i.e. bone-only metastatic disease is permitted).
  8. Patients with history of treated brain metastases are eligible if off systemic corticosteroids for at least 2 weeks.
  9. Clinical evidence for castration-resistance, with total testosterone < 50 ng/dL. Patients who have not undergone bilateral orchiectomy must plan to continue ongoing androgen deprivation therapy for the duration of the trial therapy.
  10. Patients must have adequate organ function, as confirmed by laboratory values obtained ≤ 14 calendar days prior to the first day of study therapy:

    Hematologic: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL (may have been transfused)

    Hepatic: Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and ALT levels ≤ 2.5 × ULN or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver). (Note: In subjects with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, subject may be eligible)

    Renal: Estimated creatinine clearance ≥ 45 mL/min using Cockcroft Gault formula.

  11. Patients must have a projected life expectancy of at least 3 months.

Exclusion Criteria:

  1. Prior therapy with a PARP inhibitor.
  2. Presence of clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
  3. Presence of known significant immunodeficiency, as determined by the treating investigator.
  4. Presence of clinically significant active infections, as determined by the treating investigator.
  5. Known allergy to niraparib or any of its components.
  6. Prostate cancer with histologic evidence for pure small cell histology

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04288687


Contacts
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Contact: Vivek Narayan, MD 215-360-0737 PennCancerTrials@emergingmed.com

Locations
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United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Vivek Narayan, MD    215-360-0737    PennCancerTrials@emergingmed.com   
Sponsors and Collaborators
Abramson Cancer Center of the University of Pennsylvania
Investigators
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Principal Investigator: Vivek Narayan, MD Ambramson Cancer Center of the University of Pennsylvania
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Responsible Party: Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier: NCT04288687    
Other Study ID Numbers: UPCC 21819
First Posted: February 28, 2020    Key Record Dates
Last Update Posted: February 26, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Adenocarcinoma
Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Niraparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents