Systemic and Tumor-Directed Therapy for Oligometastatic Prostate Cancer
Overview
- Phase
- Phase 2
- Intervention
- radical prostatectomy
- Conditions
- Newly Diagnosed Oligometastatic Prostate Cancer
- Sponsor
- VA Office of Research and Development
- Enrollment
- 28
- Locations
- 3
- Primary Endpoint
- Percentage of Participants With PSA<0.05ng/mL (Radical Prostatectomy) or PSA <Nadir+2ng/mL (Prostate Radiation)
- Status
- Completed
- Last Updated
- 9 months ago
Overview
Brief Summary
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) or radiation to 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) or radiation to the prostate, 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 (for patients undergoing radical prostatectomy) or PSA \<nadir+2 (for patients undergoing prostate radiation).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Biopsy confirmed diagnosis of prostate adenocarcinoma (primary small cell carcinoma of the prostate is not allowed, however adenocarcinoma with neuroendocrine differentiation is allowed)
- •Presence of 1-5 visible metastases (by NaF PET-CT or PSMA PET-CT including diagnostic CT of the chest, abdomen, and pelvis)
- •At least one metastasis must be M1a-b
- •Visceral metastases are not allowed
- •Patients may have any number of pelvic nodal metastases (but largest must be \<2 cm)
- •Metastases must be amenable to treatment with SBRT
- •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).
- •Patient must be fit to undergo radical prostatectomy, SBRT to all visible sites of metastases, ADT,
- •Total testosterone \>200 ng/dL prior to ADT (optimal time to measure total testosterone is between 8 and 9 am)
- •Adequate performance status (ECOG 0-1)
Exclusion Criteria
- •Any evidence of spinal cord compression (radiological or clinical)
- •Prior pelvic malignancy
- •Prior pelvic radiation
- •Concurrent malignancy aside from superficial skin cancers or superficial bladder tumors
- •Inability to undergo prostatectomy, radiotherapy, or ADT
- •Primary small cell carcinoma of the prostate (prostate adenocarcinoma with neuroendocrine differentiation is allowed)
- •Inflammatory bowel disease or active collagen vascular disease
- •History of any of the following:
- •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)
- •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
Arms & Interventions
Experimental Arm
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.
Intervention: radical prostatectomy
Experimental Arm
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.
Intervention: stereotactic body radiotherapy
Experimental Arm
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.
Intervention: Leuprolide
Experimental Arm
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.
Intervention: apalutamide
Experimental Arm
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.
Intervention: abiraterone
Outcomes
Primary Outcomes
Percentage of Participants With PSA<0.05ng/mL (Radical Prostatectomy) or PSA <Nadir+2ng/mL (Prostate Radiation)
Time Frame: 6 months after recovery of testosterone
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 Outcomes
- Prostate Cancer Specific Survival(up to 5 years)
- Time to Radiographic Progression(up to 5 years)
- Time to Biochemical Progression(up to 5 years)
- Time to Initiation of Additional Antineoplastic Therapy(up to 5 years)
- Patient Reported Outcomes as Assessed by Functional Assessment of Cancer Therapy - Prostate (FACT-P) Scale - Patient Questionnaire(Every 3 months up to a total of 21 months)
- Number of Participants With Treatment-related Adverse Events as Assessed by Physician Using CTCAE v4.0 Criteria(up to 5 years)