Clinical trial NCT04194554: A Multi-Center Trial of Androgen Suppression With Abiraterone Acetate, Leuprolide, PARP Inhibition and Stereotactic Body Radiotherapy in Prostate Cancer
Official title: A Multi-Center Trial of Androgen Suppression With Abiraterone aCetate, LEuprolide, PARP Inhibition and Stereotactic Body Radiotherapy (ASCLEPIuS): A Phase I/2 Trial in High Risk and Node Positive Prostate Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
Collaborators: name: Janssen Scientific Affairs, LLC
First posted: 2019-12-11
Enrollment: 102
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Time to Event Continual Reassessment Method (TITE-CRM) dose-finding clinical trial design.
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Dose-limiting toxicities (Phase 1)
timeFrame: Up to 112 days after initial dose of niraparib
measure: Proportion of patients experiencing biochemical failure
timeFrame: Up to 3 years after first dose of niraparib
Secondary outcomes:
measure: Change in health related quality of life
timeFrame: From baseline up to 3 years after last dose of niraparib
measure: Proportion of patients with undetectable post-treatment PSA
timeFrame: Measured during the end of the 6th cycle of therapy (during week 24 +/- 7 days)
measure: Proportion of patients with distant metastases
timeFrame: Up to 5 years after first dose of niraparib
measure: Prostate cancer specific survival
timeFrame: Up to 5 years after first dose of niraparib
measure: Overall survival
timeFrame: Up to 5 years after first dose of niraparib
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Rogel Cancer Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Cornell University
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Cleveland
country: United States
facility: University Hospitals Seidman Cancer Center
state: Ohio
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
Study officials:
affiliation: Case Western Reserve University - Seidman Comprehensive Cancer Center
name: Daniel Spratt, M.D.
role: STUDY_CHAIR
affiliation: University of Michigan Rogel Cancer Center
name: William Jackson, M.D.
role: PRINCIPAL_INVESTIGATOR
References: