Salvage Oligometastasectomy and Radiation Therapy in Recurrent Prostate Cancer

PRIMARY OBJECTIVES:

I. To assess response to treatment of oligometastatic disease.

SECONDARY OBJECTIVES:

I. To assess additional measurements of response to treatment of oligometastatic disease.

II. To assess prostate-specific antigen (PSA) progression free-survival following treatment
of oligometastatic disease.

III. To assess disease free-survival following treatment of oligometastatic disease.

IV. To assess time to initiation of life-long antiandrogen therapy (ADT) therapy for
metastatic prostate cancer following treatment of oligometastatic disease.

V. To assess the rate of undetectable PSA following treatment of oligometastatic disease in
subjects who have previously undergone prostatectomy.

VI. To assess the safety of the various treatment options.

Inclusion Criteria:

- Histologically proven adenocarcinoma of the prostate.

- Recurrent prostate carcinoma after definitive therapy for primary disease defined as:

- Post-prostatectomy (with/without adjuvant radiotherapy): Detectable or rising PSA
level that is > 0.2 ng/mL with a second confirmatory level of > 0.2 ng/mL after
1-4 weeks.

- Post radiotherapy/ablation (without radical prostatectomy): PSA rise >= 2ng/mL
over nadir.

- Subjects treated with prior definitive radiotherapy for prostate cancer who have a
positive 18F-fluciclovine positron emission tomography (PET) scan suggesting recurrent
intraprostatic disease must undergo transrectal ultrasound (TRUS) biopsy:

- If negative, no additional treatment is required to the prostate in addition to
that of PET positive sites.

- If positive, subject must undergo salvage prostatectomy or salvage radiotherapy
to the primary site concurrently with the study treatment.

- Oligometastatic disease defined as 5 or fewer metastatic lesions to lymph nodes and/or
bones only.

- Oligometastatic disease to pelvic or para-aortic (below inferior mesenteric artery
[IMA]) lymph nodes seen on standard of care molecular imaging (18F-fluciclovine PET
scans).

- All subjects must be surgical candidates.

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2.

- Platelet count >= 100,000 k/uL.

- Hemoglobin >= 8 g/dL.

- White blood cell (WBC) >= 2.0 k/uL.

- Total bilirubin =< 3 x upper limit of normal (ULN).

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x ULN.

- Alkaline phosphatase =< 3 x ULN.

- Prothrombin time (PT)/international normalized ratio (INR) >= 1.8 if not currently
treated with systemic anticoagulation; PT/INR >= 3.5 if currently on anticoagulation
with warfarin; PT/INR cannot be assessed if the patient is currently treated with
novel oral anticoagulants (NOAC) such as but not limited to dabigatran, rivaroxaban
and apixaban.

- Estimated creatinine clearance >= 30 mL/min as calculated from the Cockcroft-Gault
equation.

- Use of condoms for male subjects who have not had surgical removal of their prostate
and have a partner of child bearing potential beginning at the time of informed
consent form (ICF) signature and lasting until at least 6 months after the last
radiation treatment. Because of the potential side effect on spermatogenesis
associated with radiation, female partners of childbearing potential must agree to use
a highly effective contraceptive method during and for 6 months after completing
treatment.

- Recovery to baseline or =< grade 1 Common Terminology Criteria for Adverse Events
(CTCAE) version (v)4 from toxicities related to any prior treatments, unless adverse
event (AE)(s) are clinically non-significant and/or stable on supportive therapy as
determined by the treating physician.

- Able to provide informed consent and willing to sign an approved consent form that
conforms to federal and institutional guidelines.

Exclusion Criteria:

- Known brain or visceral metastases other than regional lymph nodes as defined by
computed tomography (CT), magnetic resonance imaging (MRI) or 18F PET imaging.

- Any prior systemic therapy for prostate cancer except for adjuvant treatment in the
context of localized disease.

- Subjects with > 5 bone or nodal metastases.

- Prior or concurrent invasive malignancy (except non-melanomatous skin cancer) or
lymphomatous/hematogenous malignancy unless continually disease free for a minimum of
3 years from diagnosis. All patients with in situ carcinoma are eligible for this
study (for example, carcinoma in situ of the oral cavity is eligible) except patients
with carcinoma of the bladder (including in situ bladder cancer or superficial bladder
cancer).

- Use of finasteride within 30 days prior to initiation of therapy. Baseline PSA should
not be obtained prior to 30 days after stopping finasteride.

- Use of dutasteride within 90 days prior to initiation of therapy. Baseline PSA should
not be obtained prior to 90 days after stopping dutasteride.

- Use of any prohibited therapy.

- Active, uncontrolled, significant intercurrent or recent illness including, but not
limited to, the following conditions:

- Cardiovascular disorders:

- Congestive heart failure New York Heart Association class 3 or 4, unstable
angina pectoris, serious cardiac arrhythmias.

- Uncontrolled hypertension defined as sustained blood pressure (BP) > 150
mmHg systolic or > 100 mmHg diastolic despite optimal antihypertensive
treatment.

- Stroke (including transient ischemic attack [TIA]), myocardial infarction
(MI), or other ischemic event, or thromboembolic event (e.g., deep venous
thrombosis, pulmonary embolism) within 6 months before first dose.

- Acute bacterial or fungal infection requiring intravenous antibiotics at the time
of registration

- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy at the time of registration
or within 30 days of registration.

- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.