Clinical Trials /

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

NCT04194554

Description:

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).

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2019.117
  • SECONDARY ID: HUM00167325
  • NCT ID: NCT04194554

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
NiraparibNiraparid Dose Escalation
LeuprolideNiraparid Dose Escalation
Abiraterone AcetateNiraparid Dose Escalation

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
Niraparid Dose EscalationExperimentalDose 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.
  • Niraparib
  • Leuprolide
  • Abiraterone Acetate

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 and PSA ≥10 ng/mL

               -  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 TURP, 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-limiting toxicities (Phase 1)
Time Frame:Up to 112 days after initial dose of niraparib
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Change in health related quality of life
Time Frame:From baseline up to 3 years after last dose of niraparib
Safety Issue:
Description:Assessed via EPIC-26 questionnaire
Measure: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)
Safety Issue:
Description:Undetectable PSA will be defined as a PSA ≤0.1 ng/mL.
Measure:Proportion of patients with distant metastases
Time Frame:Up to 5 years after first dose of niraparib
Safety Issue:
Description:Distant metastases will be defined as any clinical or radiographic evidence of lymph node, bone, or visceral involvement of prostate cancer.
Measure:Prostate cancer specific survival
Time Frame:Up to 5 years after first dose of niraparib
Safety Issue:
Description: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.
Measure:Overall survival
Time Frame:Up to 5 years after first dose of niraparib
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Michigan Rogel Cancer Center

Last Updated

December 9, 2019