Study of Nivolumab in Combination w Radium-223 in Men w Metastatic Castration Resistant Prostate Cancer

NCT04109729 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HCI126006
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1, open label, prospective, non-randomized single arm study combining Radium-223 with nivolumab in men with metastatic castration resistant prostate cancer.

Conditions

Metastatic Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• To assess the frequency of grade 3 or greater non-hematologic treatment-emergent adverse events when combining nivolumab with Radium-223

  Frequency of adverse events (AEs) characterized by seriousness, severity (as defined by CTCAE, version 5.0), duration, and relationship to study therapy. An increase in the clinically significant, non-hematologic grade 3 or greater toxicities above that observed in the Checkmate-214 trial will be considered unacceptable.

  From cycle one day one until cycle 3 day 28 (each cycle is 28 days) - approximately 12 weeks

• To assess the ctDNA reduction after 6 weeks of nivolumab treatment.

  Hypothesis: At least 40% of subjects with metastatic castrate resistant prostate cancer will have a Circulating tumor DNA (ctDNA) reduction after 6 weeks of therapy with Nivolumab in combination with Radium-233. An exact binomial test will be used to test the proportion of subjects with a ctDNA reduction at one-sided alpha = 0.05. The null proportion will be equal to 20%. The proportion of subjects with ctDNA reduction and 95% exact binomial confidence interval will be reported.

  From cycle one day one until cycle 4 day 15 (each cycle is 28 days) - approximately 14 weeks

Secondary Outcomes (5)

• To assess PSA progression free survival defined by the Prostate Cancer Working Group 3 (PCWG3).

  up to 24 months

• To assess correlation of bone metabolism markers with clinical response.

  From cycle one day one until cycle 4 day 15 (each cycle is 28 days) - approximately 14 weeks

• To assess response rates by serum PSA (defined by proportion of patients obtaining a 50% PSA reduction and the proportion of patients obtaining a 90% PSA reduction).

  up to 24 months

• To assess time to first symptomatic skeletal related event (defined as symptomatic fracture, surgery or radiation to bone, or spinal cord compression).

  up to 24 months

• To assess radiographic progression-free survival as defined by the PCWG3 criteria.

  up to 24 months

Study Arms (1)

All patients

EXPERIMENTAL

Radium-223 kBq/kg IV every 4 weeks for up to 6 doses. Nivolumab 480 mg IV every 4 weeks for up to 2 years.

Drug: Nivolumab; Drug: Radium-223

Interventions

Nivolumab DRUG

Nivolumab 480mg IV every 4 weeks for up to 2 years

Also known as: Opdivo

All patients

Radium-223 DRUG

Radium-223 55 kilobecquerel (kBq)/kg IV q4 weeks for 6 cycles total

Also known as: Xofigo

All patients

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male subject aged ≥ 18 years.
• Histologically confirmed adenocarcinoma of the prostate.
• Diagnosis of metastatic, castration-resistant prostate cancer without evidence of visceral metastasis.
• Symptomatic bone metastasis as determined by the treating physician.
• Castrate levels of testosterone as defined as \< 50 ng/dL.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
• Adequate organ function as defined as:
• Hematologic:
• White blood cell count (WBC) ≥ 2000/mm3
• Absolute neutrophil count (ANC) ≥ 1500/mm3
• Platelet count ≥ 100,000/mm3
• Hemoglobin ≥ 10g/dL
• Hepatic:
• Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN) unless there is a known history of Gilbert's syndrome.
• Aspartate aminotransferase (AST)(SGOT)/Alanine aminotransferase (ALT)(SGPT) ≤ 5 × institutional ULN

You may not qualify if:

• Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, hypo-or hyperthyroid disease or other autoimmune diseases in the opinion of the treating physician that is clinically insignificant or not requiring systemic immunosuppressive treatment are eligible.
• Current use of immunosuppressive medication at the time of study enrollment, EXCEPT for the following permitted steroids:
• Intranasal, inhaled, topical steroids, eye drops or local steroid injection (eg, intra-articular injection);
• Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent;
• Steroids as premedication for hypersensitivity reactions (eg, computed tomography (CT) scan premedication).
• Prior or concurrent malignancy (other than adenocarcinoma of the prostate).
• Note: Patients with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial as approved by the Principle Investigator.
• The subject has uncontrolled, significant intercurrent or recent illness that would preclude safe study participation.
• Clinically significant cardiovascular disease: myocardial infarction (\<6 months prior to enrollment), unstable angina, congestive heart failure (\> New York Heart Association Classification Class IIB) or a serious cardiac arrhythmia requiring medication.
• Known HIV infection with a detectable viral load at the time of screening.
• Note: Patients on effective antiretroviral therapy with an undetectable viral load at the time of screening are eligible for this trial.
• Known chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection with a detectable viral load.
• Note: Patients with an undetectable HBV viral load are eligible. Patients with an undetectable HCV viral load are eligible.
• Live attenuated vaccinations within 4 weeks of the first dose of radium-223 and while on trial is prohibited.
• Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v5.0 Grade ≥ 3).

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Interventions

Nivolumab; Radium-223; radium Ra 223 dichloride

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Umang Swami, MD

  Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase 1, open label, prospective, non-randomized single arm study.

Study Record Dates

• First Submitted: September 27, 2019
• First Posted: September 30, 2019
• Study Start: September 16, 2020
• Primary Completion: February 18, 2025
• Study Completion: April 30, 2026
• Last Updated: March 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)