Prostate Adenocarcinoma
Conditions
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.
Interventions
DRUGNiraparib Pill
Niraparib 200 mg by mouth daily (2 x 100 mg pills)
Sponsors
Abramson Cancer Center at Penn Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 6-Month Radiographic Progression-Free Survival (rPFS6) | 6 months from initiation of maintenance niraparib therapy | Proportion of participants alive without radiographic progression (per PCWG2 criteria), clinical deterioration (as assessed by the investigator), or death from any cause, measured from the start of maintenance niraparib therapy using Kaplan-Meier analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With PSA50 Response | From baseline until end of treatment, or up to 24 months | Number of participants achieving a ≥50% decline in serum PSA from baseline while on maintenance niraparib therapy. Participants with baseline PSA \<0.5 ng/mL will be excluded from this analysis. |
| Number of Participants With PSA30 Response | From baseline until end of treatment, or up to 24 months | Number of participants achieving a ≥30% decline in serum PSA from baseline while on maintenance niraparib therapy. Participants with baseline PSA \<0.5 ng/mL will be excluded from this analysis. |
| Time to PSA Progression | From baseline until end of treatment, or up to 24 months | Time from initiation of maintenance niraparib therapy to the first PSA increase \>25% and ≥2 ng/mL from nadir, per PCWG2 criteria. Participants with baseline PSA \<0.5 ng/mL were not evaluable. Participants without an event were censored at the last PSA assessment. |
| Overall Survival (OS) | From initiation of maintenance niraparib therapy until death from any cause, up to 36 months | Time from initiation of maintenance niraparib therapy to death from any cause, estimated by Kaplan-Meier analysis. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORVivek Narayan, MD
Ambramson Cancer Center of the University of Pennsylvania
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 68 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 9 / 11 |
| other Total, other adverse events | 11 / 11 |
| serious Total, serious adverse events | 5 / 11 |
Outcome results
None listed