Clinical Trials /

Systemic and Tumor-Directed Therapy for Oligometastatic Prostate Cancer

NCT03298087

Description:

This is a trial for patients with newly diagnosed metastatic prostate cancer with 5 or fewer sites of metastases. The trial involves surgery (removal of the prostate), six months of hormone therapy, and stereotactic body radiotherapy to the sites of metastasis.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Systemic and Tumor-Directed Therapy for Oligometastatic Prostate Cancer
  • Official Title: Systemic and Tumor-Directed Therapy for Oligometastatic Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: ONCA-013-16F
  • NCT ID: NCT03298087

Conditions

  • Newly Diagnosed Oligometastatic Prostate Cancer

Interventions

DrugSynonymsArms
LeuprolideADTExperimental Arm
apalutamideARN-509Experimental Arm
abirateronezytigaExperimental Arm

Purpose

This is a trial for patients with newly diagnosed metastatic prostate cancer with 5 or fewer sites of metastases. The trial involves surgery (removal of the prostate), six months of hormone therapy, and stereotactic body radiotherapy to the sites of metastasis.

Detailed Description

      This is a single arm Phase II clinical trial in patients with newly diagnosed M1a,b prostate
      cancer and 1-5 radiographically visible metastases treated with radical prostatectomy (and
      post-operative fractionated radiotherapy for pT 3a, pN1, or positive margins), metastasis
      directed SBRT, and complete ADT with LHRH analog leuprolide, abiraterone acetate with
      prednisone, and apalutamide (ARN-509) for a total of six months of systemic therapy. The
      primary endpoint of our study is the percent of patients achieving a serum PSA of <0.05 ng/mL
      six months after recovery of serum testosterone.
    

Trial Arms

NameTypeDescriptionInterventions
Experimental ArmExperimentalRadical prostatectomy (and post-operative fractionated radiotherapy for pT=3a, pN1, or positive margins), metastasis directed SBRT, and complete ADT with LHRH analog leuprolide, abiraterone acetate with prednisone, and apalutamide (ARN-509) for a total of six months of systemic therapy.
  • Leuprolide
  • apalutamide
  • abiraterone

Eligibility Criteria

        Inclusion Criteria:

          1. Biopsy confirmed diagnosis of prostate adenocarcinoma (primary small cell carcinoma of
             the prostate is not allowed, however adenocarcinoma with neuroendocrine
             differentiation is allowed)

          2. Age 18

          3. Presence of 1-5 visible metastases (by NaF PET-CT or PSMA PET-CT including diagnostic
             CT of the chest, abdomen, and pelvis)

               1. At least one metastasis must be M1a-b

               2. Visceral metastases are not allowed

               3. Patients may have any number of pelvic nodal metastases (but largest must be <2
                  cm)

               4. Metastases must be amenable to treatment with SBRT

               5. Biopsy of one metastasis must be attempted, unless unsafe to perform. If biopsy
                  is not diagnostic, or unsafe to perform, then a secondary imaging modality (for
                  example, MRI) must also be consistent with metastatic disease (unless PSMA PET-CT
                  was used as initial staging).

          4. Patient must be fit to undergo radical prostatectomy, SBRT to all visible sites of
             metastases, ADT,

          5. Total testosterone >200 ng/dL prior to ADT (optimal time to measure total testosterone
             is between 8 and 9 am)

          6. Adequate performance status (ECOG 0-1)

          7. Clinical laboratory values at screening:

               1. Hemoglobin 9.0 g/dL, independent of transfusion and/or growth factors within 3
                  months prior to randomization

               2. Platelet count 100,000 x 109/ L independent of transfusion and/or growth factors
                  within 3 months prior to randomization

               3. Serum albumin 3.0 g/dL

               4. GFR 45 mL/min

               5. Serum potassium 3.5 mmol/L

               6. Serum total bilirubin 1.5 ULN (Note: In subjects with Gilbert's syndrome, if
                  total bilirubin is >1.5 ULN, measure direct and indirect bilirubin and if direct
                  bilirubin is 1.5 ULN, subject may be eligible)

               7. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <2.5 ULN

          8. Medications known to lower the seizure threshold (see list under prohibited
             medications) must be discontinued or substituted at least 4 weeks prior to study
             entry.

        Exclusion Criteria:

          1. Any evidence of spinal cord compression (radiological or clinical)

          2. Prior pelvic malignancy

          3. Prior pelvic radiation

          4. Concurrent malignancy aside from superficial skin cancers or superficial bladder
             tumors

          5. Inability to undergo prostatectomy, radiotherapy, or ADT

          6. Primary small cell carcinoma of the prostate (prostate adenocarcinoma with
             neuroendocrine differentiation is allowed)

          7. Inflammatory bowel disease or active collagen vascular disease

          8. History of any of the following:

               1. Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke
                  within 1year to randomization, brain arteriovenous malformation, Schwannoma,
                  meningioma, or other benign CNS or meningeal disease which may require treatment
                  with surgery or radiation therapy)

               2. Severe or unstable angina, myocardial infarction, symptomatic congestive heart
                  failure, arterial or venous thromboembolic events (eg, pulmonary embolism,
                  cerebrovascular accident including transient ischemic attacks), or clinically
                  significant ventricular arrhythmias within 6 months prior to randomization

          9. Current evidence of any of the following:

               1. Uncontrolled hypertension

               2. Gastrointestinal disorder affecting absorption

               3. Active infection (eg, human immunodeficiency virus [HIV] or viral hepatitis)

               4. Any chronic medical condition requiring a higher dose of corticosteroid than 10
                  mg prednisone/prednisolone once daily

               5. Any condition that in the opinion of the investigator would preclude
                  participation in this study

               6. Concomitant strong CYP3A4 inducers. (If a strong CYP3A4 inducer must be
                  co-administered, abiraterone acetate dose frequency will be adjusted).

               7. Treatment with CYP2D6 substrates that have a narrow therapeutic index. If an
                  alternative treatment cannot be used, a dose reduction of the CYP2D6 substrate
                  may be considered.

               8. Baseline severe hepatic impairment (ChildPugh Class B & C)

         10. Presence of visceral metastases (i.e., stage M1c)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:PSA<0.05ng/mL
Time Frame:6 months after recovery of testosterone
Safety Issue:
Description:PSA is a biomarker for disease burden in prostate adenocarcinoma and offers a non-invasive and sensitive assessment of disease control after treatment in the vast majority of patients.

Secondary Outcome Measures

Measure:time to biochemical progression
Time Frame:up to 5 years
Safety Issue:
Description:biochemical, radiographic, or clinical
Measure:Time to radiographic progression
Time Frame:up to 5 years
Safety Issue:
Description:per PCWG3 criteria
Measure:Time to initiation of additional antineoplastic therapy
Time Frame:up to 5 years
Safety Issue:
Description:antineoplastic therapy includes any systemic or focal anti-prostate cancer therapy
Measure:Prostate cancer specific survival
Time Frame:up to 5 years
Safety Issue:
Description:Prostate cancer specific survival
Measure:Patient reported outcomes as assedded by Functional Assessment of Cancer Therapy - Prostate (FACT-P) scale - patient questionnaire
Time Frame:up to 5 years
Safety Issue:
Description:This uses the Functional Assessment of Cancer Therapy - Prostate (FACT-P) questionnaire. It assesses patient function in four domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by 12 site specific items to assess for prostate related symptoms. Items are rated on a 0 to 4 Likert type scale and combined to produce subscale scores for each domain and a global score, the higher the score, the better the quality of life. Range from 0-150 . Data will be aggregated per patient and over time.
Measure:Number of participants with treatment-related adverse events as assessed by physician using CTCAE v4.0 criteria
Time Frame:up to 5 years
Safety Issue:
Description:CTCAE v4 criteria are a set of criteria for the standardized classification of adverse effects cancer therapy. The CTCAE system is a product of the US National Cancer Institute. The criteria are assessed by physician. The grades range from 0 to 5 (higher is worse). Data will be aggregated per patient and over time and classified by organ system (e.g., genitourinary, gastrointestinal, etc).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:VA Office of Research and Development

Trial Keywords

  • oligometastatic
  • SBRT
  • abiraterone
  • apalutamide

Last Updated

September 24, 2019