A Multi-Center Trial of Androgen Suppression With Abiraterone Acetate, Leuprolide, PARP Inhibition and Stereotactic Body Radiotherapy in Prostate Cancer

Prostate Cancer Clinical Trial

— ASCLEPIuS  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04194554
• Other study ID #: UMCC 2019.117
• Secondary ID: HUM00167325
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 6, 2020
• Est. completion date: May 2027

Study information

• Verified date: September 2023
• Source: University of Michigan Rogel Cancer Center
• Contact: UM Cancer AnswerLine
• Phone: 800-865-1125
• Email: CancerAnswerLine[@]med.umich.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: May 2027
• Est. primary completion date: November 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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 90 days thereafter. Men must also agree not to donate sperm for the duration of the study participation, and for at least 90 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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Niraparib
given PO per dose escalation schedule
• Leuprolide
22.5 mg q3 month
• Abiraterone Acetate
1000 mg daily

Radiation:
• Stereotactic body radiotherapy (SBRT)
5-6 fraction SBRT (total dose: 37.5-40 Gy)

Locations

Country	Name	City	State
United States	University of Michigan Rogel Cancer Center	Ann Arbor	Michigan
United States	University Hospitals Seidman Cancer Center	Cleveland	Ohio
United States	University of Texas Southwestern	Dallas	Texas
United States	Cornell University	New York	New York
United States	Weill Cornell Medicine	New York	New York
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
University of Michigan Rogel Cancer Center	Janssen Scientific Affairs, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicities (Phase 1)	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.	Up to 112 days after initial dose of niraparib
Primary	Proportion of patients experiencing biochemical failure	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.	Up to 3 years after first dose of niraparib
Secondary	Change in health related quality of life	Assessed via EPIC-26 questionnaire	From baseline up to 3 years after last dose of niraparib
Secondary	Proportion of patients with undetectable post-treatment PSA	Undetectable PSA will be defined as a PSA =0.1 ng/mL.	Measured during the end of the 6th cycle of therapy (during week 24 +/- 7 days)
Secondary	Proportion of patients with distant metastases	Distant metastases will be defined as any clinical or radiographic evidence of lymph node, bone, or visceral involvement of prostate cancer.	Up to 5 years after first dose of niraparib
Secondary	Prostate cancer specific survival	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.	Up to 5 years after first dose of niraparib
Secondary	Overall survival	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.	Up to 5 years after first dose of niraparib