Patient case: 50-year-old male with prostate cancer; genetic feature: ATM deletion

Clinical trial: Salvage Oligometastasectomy and Radiation Therapy in Recurrent Prostate Cancer

Summary: This phase II trial studies how well surgery and radiation therapy work in treating patients with prostate cancer that has come back or spread to other parts of the body. Radiation therapy uses high energy beams to kill tumor cells and shrink tumors. Surgical procedures, such as oligometastasectomy, may remove tumor cells that have spread to other parts of the body. Surgery and radiation therapy may work better in treating patients with prostate cancer that has come back or spread to other parts of the body.

Detailed description: 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.

Eligibility: 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.

Relevance to patient case: not relevant