Radium-223 and Radiotherapy in Hormone-Naïve Men With Oligometastatic Prostate Cancer to Bone
Condition: Prostate Cancer Metastatic to Bone
MeSH terms: Prostatic Neoplasms
Intervention: Radium Ra 223 Dichloride; Radiation
Intervention description: Radium Ra 223 dichloride will be delivered intravenously at 55 kBq/kg (1.49 mCi)/kg (+/- 10% total dose) for a total of six cycles. 1 cycle= 28 days. The first cycle will commence at study enrollment, then cycles 2-6 will commence after the completion of radiotherapies at 4 week intervals; All external beam radiations oligometastatic sites will commence after cycle 1 of Radium-223 but prior to cycle 2 of Radium-223. All subjects will receive Stereotactic body or hypofractionated radiation to sites of bone disease seen on imaging studies. Patients will have the primary tumor sites and 5 or fewer sites of bone-only metastasis treated with external beam radiation.
Any of the following regimens are considered ablative, acceptable and are biologically equivalent to 60Gy EQD2:
Single fraction: 16 Gy total at 16 Gy per fraction (SBRT)
Three fractions: 24 Gy total at 8 Gy per fraction (SBRT)
Five fractions: 30 Gy total at 6Gy per fraction (SBRT).When using five fractions, can reduce to 25 Gy total at 5 Gy per fraction (SBRT) or to a minimum of 20 Gy total at 4 Gy per fraction (SBRT), per treating investigator.
Six fractions: 32.4 Gy total at 5.4Gy per fraction (Hypofractionated)
Intervention MeSH terms: Radium Ra 223 dichloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: This is a phase IIa, open label, single arm, prospective study
Masking: None (Open Label)
Enrollment: 20.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a phase IIa, open label, single arm, and prospective study of hormone therapy-naïve
      men with oligometastatic prostate cancer to the bone. The study will test if treating the
      primary tumor sites and 5 or fewer sites of bone-only metastasis with external beam radiation
      with concomitant systemic Radium-223 will reduce the utilization of androgen deprivation
      therapy, improve QOL and improve OS over a the comparator cohort of SWOG intermittent ADT
      historic cohort.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Asymptomatic or symptomatic hormone naïve men with testosterone levels ≥100 ng/dL with
             previously treated localized prostate cancer who now have rising PSA's and five or
             fewer bone metastases.

          -  Subjects who have been previously treated with definitive and/or adjuvant/salvage
             radiotherapy to the primary site and/or regional lymph nodes with concurrent ADT are
             allowed if the last hormone therapy delivered > 6 months prior. Subjects who have had
             more than 30 days and fewer than 45 days of bicalutamide monotherapy for any reason
             within the 6 months prior to enrollment are eligible for the study, providing they
             have been off of the drug for at least 30 days prior to enrollment. Subjects who have
             had fewer than 30 days of bicalutamide are eligible for the study, as long as they
             discontinue the drug at least 5 days prior to the first study treatment.

          -  Histologic confirmation of Prostate Adenocarcinoma diagnosis.

          -  Age ≥ 18 years.

          -  Life expectancy of at least 2 years.

          -  Acceptable hematology and serum biochemistry screening values:

               -  White Blood Cell Count (WBC) ≥ 3,000/mm3

               -  Absolute Neutrophil Count (ANC) ≥ 1,500/mm3

               -  Platelet (PLT) count ≥ 100,000/mm3

               -  Hemoglobin (HGB) ≥ 10 g/dl

               -  Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN)

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN

               -  Creatinine ≤ 1.5 x ULN

               -  Albumin > 2.5 mg/dL

          -  Willing and able to comply with the protocol, including follow-up visits and
             examinations.

          -  Karnofsky Performance Score >60 or ECOG equivalent.

          -  Radiographic confirmation of oligometastatic diagnosis via Bone Scan validated by
             either CT scan or MRI or PET/CT with Fluciclovine within the past 90 days.

          -  Subjects who have not had surgical removal of their prostate and have a partner of
             child bearing potential must agree to use condoms beginning at the signing of the ICF
             until at least 6 months after the last dose of study drug. 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

          -  Able to provide informed consent and willing to sign an approved consent form that
             conforms to federal and institutional guidelines.

        Exclusion Criteria:

          -  Men with known brain or visceral metastases (except regional lymph nodes as defined by
             section 5.2.5) defined by CT or MRI Imaging of the abdomen or pelvis.

          -  Men who have had LHRH agonist or antagonist hormone therapy in the prior six months.

          -  Men with >5 bony metastases.

          -  Men with baseline serum Testosterone <100 ng/dL.

          -  Men with new or progressing lymphadenopathy clearly consistent with prostate
             metastasis on imaging or proven by pathologic biopsy at any time three months or later
             following their initial definitive therapy.

          -  Prior or concurrent invasive malignancy (except non-melanomatous skin cancer) or
             lymphomatous/hematogenous malignancy unless continually disease free for a minimum of
             3 years. 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 therapy PSA should not be obtained prior to
             30 days after stopping finasteride.

          -  Use of dutasteride within 90 days prior to therapy. PSA should not be obtained prior
             to 90 days after stopping dutasteride.

          -  Previous or concurrent cytotoxic chemotherapy for prostate cancer.

          -  Received systemic therapy with radionuclides (e.g., strontium-89, samarium-153,
             rhenium-186, or rhenium-188, or Radium Ra 223 dichloride) for the treatment of bony
             metastases.

          -  Men who will receive radical prostatectomy to the primary site.

          -  Imminent spinal cord compression based on clinical findings and/or magnetic resonance
             imaging (MRI). Spinal Cord compression will be defined as 360 degree circumferential
             obliteration of T2 cerebrospinal fluid signal around the spinal cord. Treatment should
             be completed for spinal cord compression.

          -  Severe, active co-morbidity, defined as follows:

               -  Unstable angina and/or congestive heart failure requiring hospitalization within
                  the last 6 months

               -  Transmural myocardial infarction within the last 6 months

               -  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

               -  Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
                  note, however, that laboratory tests for liver function and coagulation
                  parameters are not required for entry into this protocol. (Patients on Coumadin
                  or other blood thinning agents are eligible for this study.)

               -  Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition;
                  note, however, that HIV testing is not required for entry into this protocol. The
                  need to exclude patients with AIDS from this protocol is necessary because the
                  treatments involved in this protocol may be significantly immunosuppressive.

          -  Cardiac failure New York Heart Association (NYHA) III or IV Crohn's disease or
             ulcerative colitis.

          -  Bone marrow dysplasia.

          -  Fecal incontinence.

          -  Any condition which, in the investigator's opinion, makes the subject unsuitable for
             trial participation.