Clinical Trials /

Radium-223 and Radiotherapy in Hormone-Naïve Men With Oligometastatic Prostate Cancer to Bone

NCT03304418

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Radium-223 and Radiotherapy in Hormone-Naïve Men With Oligometastatic Prostate Cancer to Bone
  • Official Title: A Phase 2 Study of Radium-223 and Radiotherapy in Hormone-Naïve Men With Oligometastatic Prostate Cancer to Bone

Clinical Trial IDs

  • ORG STUDY ID: HCI102312
  • NCT ID: NCT03304418

Conditions

  • Prostate Cancer Metastatic to Bone

Interventions

DrugSynonymsArms
Radium Ra 223 DichlorideXofigoRadium Ra 223 dichloride and radiation, all patients

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Radium Ra 223 dichloride and radiation, all patientsExperimental
  • Radium Ra 223 Dichloride

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
             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.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Time to Androgen Deprivation Therapy (ADT) Use
Time Frame:15 months
Safety Issue:
Description:Determine if 20% of ADT naïve men treated with concurrent EBRT and Radium-223 will not require ADT for progression by 15 months. Endpoint: Determine the time from start of study therapy to start of ADT.

Secondary Outcome Measures

Measure:Time from start of study therapy to start of ADT.
Time Frame:2 years
Safety Issue:
Description: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 SWOG intermittent ADT historic cohort
Measure:Evaluate health related quality of life (QOL)
Time Frame:This questionnaire will be given every 3 months for 2 years
Safety Issue:
Description: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.
Measure:Evaluate changes in general function and well being
Time Frame:This questionnaire will be given every 3 months for 2 years
Safety Issue:
Description:Evaluate health related quality of life (QOL)- the PROMIS 29 will be used to assess general function and well-being
Measure:Evaluate time to first skeletal related event (SRE)
Time Frame:2 years
Safety Issue:
Description:Documentation of complications associated with bone metastases and may include (but not limited to) fractures, spinal cord compression, bone pain, and hypercalcemia.
Measure:Evaluate the PSA doubling time
Time Frame:2 years, assessed at every visit in that time period
Safety Issue:
Description:Time elapsed from baseline PSA to double in value.
Measure:Evaluate Overall Surival
Time Frame:2 years
Safety Issue:
Description:Evaluate overall survival at 2 years relative to the SWOG intermittent ADT historic cohort. Endpoint: Patients will be followed for survival for two years after study enrollment

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Utah

Last Updated

October 1, 2019