Prostate Cancer
Conditions
Brief summary
The purpose of this study is to establish the maximum tolerable dose of niraparib when combined with prostate stereotactic body radiotherapy (SBRT), abiraterone, leuprolide, and prednisone (the phase 1 portion of the study) and determine 3-year biochemical PSA recurrence free-survival with this treatment approach (the phase 2 portion of the study).
Interventions
DRUGNiraparib
given PO per dose escalation schedule
DRUGLeuprolide
22.5 mg q3 month
DRUGAbiraterone Acetate
1000 mg daily
RADIATIONStereotactic body radiotherapy (SBRT)
5-6 fraction SBRT (total dose: 37.5-40 Gy)
Sponsors
University of Michigan Rogel Cancer Center
Janssen Scientific Affairs, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Time to Event Continual Reassessment Method (TITE-CRM) dose-finding clinical trial design.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Pathologic biopsy proven adenocarcinoma of the prostate 2. At least one of the following criteria: * cN1 on conventional or PET imaging * Grade group 5 * Grade group 4 * Grade group 3 and PSA ≥20 ng/mL * High probability of Radiographic T3 on MRI AND Grade group ≥2 * Grade Group 3 AND PSA ≥10 ng/mL AND ≥50% positive biopsy cores 3. Age ≥ 18 4. ECOG \< 1 5. Adequate organ and marrow function as defined per protocol. 6. Use of highly effective contraception (e.g. condoms) for the duration of treatment and a minimum of 120 days thereafter. Men must also agree not to donate sperm for the duration of the study participation, and for at least 120 days thereafter. 7. International Prostate Symptoms Score (IPSS) ≤ 20 8. Medically fit for treatment and agreeable to follow-up 9. Ability to understand and the willingness to sign a written informed consent 10. Tissue available for MiOncoSeq testing to assign DNA repair deficiency status
Exclusion criteria
1. Clinical or radiographic evidence of distant metastatic disease by CT/bone scan 2. Clinical or radiographic evidence of high probability of clinical T4 disease 3. Prostate gland size \>80 cc measured by ultrasound or MRI 4. Prominent median lobe assessed by treating physician 5. Lack of tissue from biopsy to be sent for correlative studies 6. Any prior treatment for prostate cancer (incudes history of TURP within 5 years of enrollment, chemotherapy, radiation therapy, or anti-androgen therapy) 7. Prohibited within 30 days prior to administration to study treatment: spironolactone and other investigational drug therapies. 8. Prohibited 3 months before participant registration and during administration of study treatment: non-steroidal anti-androgens (e.g., bicalutamide, flutamide, nilutamide), steroidal antiandrogens (megestrol acetate, cyproterone acetate), oral ketoconazole, chemotherapy, immunotherapy, estrogens, radiopharmaceuticals. 9. History of prior pelvic radiation therapy 10. Concurrent treatment with strong CYP3A4 inducers such as phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital 11. Enrollment concurrently in another investigational drug study within 1 month of registration 12. History of another active malignancy within the previous 3 years except for adequately treated skin cancer or superficial bladder cancer 13. History of or active Crohn's disease or ulcerative colitis 14. Contraindication to or inability to tolerate MRIs 15. Patients with severe depression 16. Uncontrolled diabetes or known HbA1c\>10 17. Any gastrointestinal disorder affecting absorption 18. Active pituitary or adrenal dysfunction 19. Patients with significant cardiovascular disease potentially including severe / unstable angina, recent history of myocardial infarction, clinically significant heart failure, cerebrovascular disease, venous thromboembolic events, clinically significant arrhythmias) 20. Uncontrolled hypertension with persistently elevated systolic blood pressure \>160 mmgHg or diastolic blood pressure \>100 mmHg despite anti-hypertensive agents. 21. Prolonged QTc \>450 ms or any ECG changes that interfere with QT interval interpretation 22. Major surgery within 1 month of registration 23. History of myelodysplastic syndrome or leukemia 24. A known hypersensitivity to niraparib, abiraterone acetate, leuprolide, and/or prednisone 25. Active infection or other medical condition that would be a contraindication to prednisone use 26. Patients with known active hepatitis or chronic liver disease including cirrhosis 27. Any condition that in the opinion of the investigator would preclude participation in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicities (Phase 1) | Up to 112 days after initial dose of niraparib | The proportion of patients at each dose level with dose-limiting toxicity (DLT), defined as any treatment related grade 3-5 adverse event experienced within the first 4 treatment cycles (112 days), assessed per NCI's CTCAE version 5.0. |
| Proportion of patients experiencing biochemical failure | Up to 3 years after first dose of niraparib | Change in PSA level from the beginning of study treatment for up to 3 years later will determine the biochemical failure rate. Biochemical failure will be defined using the Phoenix definition of the PSA nadir + 2 ng/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in health related quality of life | From baseline up to 3 years after last dose of niraparib | Assessed via EPIC-26 questionnaire |
| Proportion of patients with undetectable post-treatment PSA | Measured during the end of the 6th cycle of therapy (during week 24 +/- 7 days) | Undetectable PSA will be defined as a PSA ≤0.1 ng/mL. |
| Proportion of patients with distant metastases | Up to 5 years after first dose of niraparib | Distant metastases will be defined as any clinical or radiographic evidence of lymph node, bone, or visceral involvement of prostate cancer. |
| Prostate cancer specific survival | Up to 5 years after first dose of niraparib | Prostate cancer specific survival will be defined as the duration of time from the start of treatment to death attributable to prostate cancer. Patients who have not died or die of non-prostate cancer related causes will be censored at the last known follow-up or date of death, respectively. Summarized using cumulative incidence or Kaplan-Meier curves as appropriate. |
| Overall survival | Up to 5 years after first dose of niraparib | Overall survival (OS) will be defined as the duration of time from the start of treatment to death from any cause. Patients who have not died will be censored at the last known follow-up.Summarized using cumulative incidence or Kaplan-Meier curves as appropriate. |
Countries
United States
Contacts
STUDY_CHAIRDaniel Spratt, M.D.
Case Western Reserve University - Seidman Comprehensive Cancer Center
PRINCIPAL_INVESTIGATORWilliam Jackson, M.D.
University of Michigan Rogel Cancer Center
Outcome results
None listed