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

• Sponsor: University of Utah
• Collaborator: Bayer
• Information provided by (Responsible Party): University of Utah

Tracking Information

• First Submitted Date: September 27, 2017
• First Posted Date: October 9, 2017
• Last Update Posted Date: September 20, 2018
• Actual Study Start Date: February 12, 2018
• Estimated Primary Completion Date: November 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 2, 2017)

Time to Androgen Deprivation Therapy (ADT) Use [ Time Frame: 15 months ]

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.

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03304418 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: October 2, 2017)

• Time from start of study therapy to start of ADT. [ Time Frame: 2 years ]
  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
• Evaluate health related quality of life (QOL) [ Time Frame: This questionnaire will be given every 3 months for 2 years ]
  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.
• Evaluate changes in general function and well being [ Time Frame: This questionnaire will be given every 3 months for 2 years ]
  Evaluate health related quality of life (QOL)- the PROMIS 29 will be used to assess general function and well-being
• Evaluate time to first skeletal related event (SRE) [ Time Frame: 2 years ]
  Documentation of complications associated with bone metastases and may include (but not limited to) fractures, spinal cord compression, bone pain, and hypercalcemia.
• Evaluate the PSA doubling time [ Time Frame: 2 years, assessed at every visit in that time period ]
  Time elapsed from baseline PSA to double in value.
• Evaluate Overall Surival [ Time Frame: 2 years ]
  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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• Brief 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Intervention Model: Single Group Assignment
Intervention Model Description:

This is a phase IIa, open label, single arm, prospective study

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Prostate Cancer Metastatic to Bone

Intervention

• Drug: Radium Ra 223 Dichloride
  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
  Other Name: Xofigo
• Radiation: Radiation

  All external beam radiations oligometastatic sites will commence 1 to 2 weeks after administration of Cycle 1 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)
  • Six fractions: 32.4 Gy total at 5.4Gy per fraction (Hypofractionated)

Study Arms

Experimental: Radium Ra 223 dichloride and radiation, all patients

Interventions:

• Drug: Radium Ra 223 Dichloride
• Radiation: Radiation

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 2, 2017): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 2022
• Estimated Primary Completion Date: November 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Brett Johnson; 801-587-4429; brett.johnson@hci.utah.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03304418
• Other Study ID Numbers: HCI102312
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

• IPD Sharing Statement: Not Provided
• Responsible Party: University of Utah
• Study Sponsor: University of Utah
• Collaborators: Bayer
• Investigators: Not Provided
• PRS Account: University of Utah
• Verification Date: September 2018