Radium Ra 223 Dichloride and External Beam Radiation Therapy in Treating Patients with Prostate Cancer Metastatic in the Bone

Status: Active

Description

This phase II trial studies how well radium Ra 223 dichloride and external beam radiation therapy work in treating patients with prostate cancer that has spread to the bone. Radioactive drugs, such as radium Ra 223 dichloride, may carry radiation directly to tumor cells and not harm normal cells. Radiation therapy uses high energy beams to kill tumor cells and shrink tumors. Giving radium Ra 223 dichloride and external beam radiation therapy together may work better in treating patients with prostate cancer.

Eligibility Criteria

Inclusion Criteria

  • Asymptomatic or symptomatic hormone naive 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 fewer than 6 weeks 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
  • Histologic confirmation of prostate adenocarcinoma diagnosis
  • Life expectancy of at least 2 years
  • White blood cell count (WBC) >= 3,000/mm^3
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelet (PLT) count >= 100,000/mm^3
  • 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 Eastern Cooperative Oncology Group (ECOG) equivalent
  • Radiographic confirmation of oligometastatic diagnosis via bone scan validated by either computed tomography (CT) scan, or magnetic resonance imaging (MRI) or positron emission tomography (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 informed consent form (ICF) until at least 6 months after the last dose of study drug; 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) defined by CT or MRI imaging of the abdomen or pelvis
  • Men who have had gonadotrophin releasing hormone (LHRH) agonist or antagonist hormone therapy in the prior six months
  • Men with > 5 validated 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 Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary
  • 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

Locations & Contacts

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: Active
Contact: Jonathan D. Tward
Phone: 801-585-0255
Email: jonathan.tward@hci.utah.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. Determine if 20% of androgen deprivation therapies (ADT) naive men treated with concurrent external beam radiation therapy (EBRT) and radium Ra 223 dichloride (radium-223) will not require ADT for progression by 15 months.

SECONDARY OBJECTIVES:

I. Determine the hormone-therapy free survival time for men treated with concurrent EBRT and radium-223 and determine if it is a 30% risk reduction over the Southwest Oncology Group (SWOG) intermittent ADT historic cohort.

II. Evaluate health related quality of life (QOL) as scored by the 50 item Expanded Prostate Inventory Composite (EPIC) EPIC urinary, bowel, sexual and hormonal domains.

III. Evaluate time to first skeletal related event (SRE).

IV. Evaluate the prostate specific antigen (PSA) doubling time.

V. Evaluate overall survival at 2 years relative to the SWOG intermittent ADT historic cohort.

VI. Evaluate Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 toxicities in the study population.

EXPLORATORY OBJECTIVES:

I. Evaluate if a commercially available cell-cycle progression gene assay (Myriad cell cycle proliferation [CCP]) performed on the original prostate biopsy or surgical pathology specimen correlates with biochemical or clinical progression free survival in the study population.

II. Evaluate if a commercially available homologous recombination deoxyribonucleic acid (DNA) repair assay correlates with biochemical or clinical progression free survival in the study population (Myriad homologous recombination deficiency [HRD]).

OUTLINE:

Patients receive radium Ra 223 dichloride intravenously (IV) over up to 1 minute on day 1. After 1-2 weeks, patients undergo EBRT for 4-6 weeks. Patients continue to receive radium Ra 223 dichloride concurrently with EBRT. Treatment with radium Ra 223 dichloride repeats every 28 days for 6 cycles in the absence of disease progression or unaccepted toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Huntsman Cancer Institute / University of Utah

Principal Investigator
Jonathan D. Tward

Trial IDs

Primary ID HCI102312
Secondary IDs NCI-2018-00295
Clinicaltrials.gov ID NCT03304418