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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04194554
Recruitment Status : Recruiting
First Posted : December 11, 2019
Last Update Posted : October 19, 2022
Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

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).

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Niraparib Drug: Leuprolide Drug: Abiraterone Acetate Radiation: Stereotactic body radiotherapy (SBRT) Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Time to Event Continual Reassessment Method (TITE-CRM) dose-finding clinical trial design.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 6, 2020
Estimated Primary Completion Date : November 2026
Estimated Study Completion Date : May 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Niraparid Dose Escalation

Dose Level 1: 100 mg PO daily of Niraparib but held for 5 days (+/- 2 days) prior to RT, during SBRT, and 5 days (+/- 2 days) after last fraction of SBRT

Dose Level 2: 200 mg PO daily of Niraparib but held for 5 days (+/- 2 days) prior to RT, during SBRT, and 5 days (+/- 2 days) after last fraction of SBRT

Dose Level 3: 200 mg PO daily of Niraparib without breaks during SBRT until completion of 6 cycles.

Drug: Niraparib
given PO per dose escalation schedule

Drug: Leuprolide
22.5 mg q3 month

Drug: Abiraterone Acetate
1000 mg daily

Radiation: Stereotactic body radiotherapy (SBRT)
5-6 fraction SBRT (total dose: 37.5-40 Gy)
Other Name: Ultra-hypofractionated radiotherapy

Primary Outcome Measures :
  1. Dose-limiting toxicities (Phase 1) [ Time Frame: 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.

  2. Proportion of patients experiencing biochemical failure [ Time Frame: 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 Outcome Measures :
  1. Change in health related quality of life [ Time Frame: From baseline up to 3 years after last dose of niraparib ]
    Assessed via EPIC-26 questionnaire

  2. Proportion of patients with undetectable post-treatment PSA [ Time Frame: 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.

  3. Proportion of patients with distant metastases [ Time Frame: 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.

  4. Prostate cancer specific survival [ Time Frame: 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.

  5. Overall survival [ Time Frame: 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts 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 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

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 identifier (NCT number): NCT04194554

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Contact: UM Cancer AnswerLine 800-865-1125

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United States, Michigan
University of Michigan Rogel Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Cancer AnswerLine    800-865-1125   
Principal Investigator: William Jackson, M.D.         
United States, New York
Weill Cornell Medicine Recruiting
New York, New York, United States, 10065
Contact: Sharanya Chandrasekhar, M.S.    646-962-2196   
Contact: Pragya Yadav, Ph.D.    646-962-2199   
Principal Investigator: Himanshu Nagar, M.D.         
United States, Ohio
University Hospitals Seidman Cancer Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Daniel Spratt, MD    216-293-6191   
Principal Investigator: Daniel Spratt, MD         
United States, Texas
University of Texas Southwestern Recruiting
Dallas, Texas, United States, 75390
Contact: Cancer AnswerLine at UTSW    833-722-6237   
Principal Investigator: Neil Desai, MD, MHS         
Sponsors and Collaborators
University of Michigan Rogel Cancer Center
Janssen Scientific Affairs, LLC
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Study Chair: Daniel Spratt, M.D. Case Western Reserve University - Seidman Comprehensive Cancer Center
Principal Investigator: William Jackson, M.D. University of Michigan Rogel Cancer Center
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Responsible Party: University of Michigan Rogel Cancer Center Identifier: NCT04194554    
Other Study ID Numbers: UMCC 2019.117
HUM00167325 ( Other Identifier: University of Michigan )
First Posted: December 11, 2019    Key Record Dates
Last Update Posted: October 19, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data that may be shared will only include individual participant data that underlie the results reported publicly in or published articles, after deidentification (text, tables, figures, appendices).
Supporting Materials: Study Protocol
Time Frame: The time frame for data sharing will begin 12 months after the initial publication and continue until 36 months after publication in
Access Criteria: Once the final results of the trial have been reported parties interested in accessing the data should contact the trial PI (Dr. Daniel Spratt) to discuss any potential data sharing requests. An analysis plan is required and intended use of the data must be disclosed. Only de-identified data may be shared and all agreements must comply with current policies of both parties to share data.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Genital Diseases
Urogenital Diseases
Prostatic Diseases
Male Urogenital Diseases
Abiraterone Acetate
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Cytochrome P-450 Enzyme Inhibitors
Poly(ADP-ribose) Polymerase Inhibitors