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

• Status: Recruiting
• Trial end date: 2024-06-15
• Target enrollment: 0
• Participant gender: Male

Summary

This is an open label, prospective, trial that begins with a phase Ib safety run-in followed by a phase II expansion cohort.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Utah
• Treatments: Nivolumab

Criteria

Inclusion Criteria:

• 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.

• 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.

• AST(SGOT)/ALT(SGPT) ≤ 5 × institutional ULN

• Renal:

• Estimated creatinine clearance ≥ 30 mL/min by Cockcroft-Gault formula:

• Males: ((140-age)×weight[kg])/(serum creatinine [mg/dL]×72)

• Highly effective contraception throughout the study and for at least 7 months after last study treatment administration if the risk of conception exists.

• Recovery to baseline or ≤ Grade 1 CTCAE v 5.0 from toxicities related to any prior treatments, unless AE(s) are clinically non-significant and/or stable on supportive therapy as determined by the treating physician.

• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Exclusion Criteria:

• 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).

• Subjects taking prohibited medications as described in Section 6.4.1. A washout period of prohibited medications for a period of at least 5 half-lives or as clinically indicated should occur prior to the start of treatment.