Metastatic Castration-resistant Prostate Cancer Clinical Trial
— Rad2NivoOfficial title:
A Phase IB Study of Nivolumab in Combination With Radium-223 in Men With Metastatic Castration Resistant Prostate Cancer
This is an open label, prospective, trial that begins with a phase Ib safety run-in followed by a phase II expansion cohort.
Status | Recruiting |
Enrollment | 36 |
Est. completion date | April 30, 2026 |
Est. primary completion date | April 30, 2025 |
Accepts healthy volunteers | No |
Gender | Male |
Age group | 18 Years and older |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
United States | Huntsman Cancer Institute at University of Utah | Salt Lake City | Utah |
Lead Sponsor | Collaborator |
---|---|
University of Utah |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Phase Ib:To assess the safety of nivolumab in combination w Radium-223 in patients w metastatic castrate resistant prostate cancer. | Hypothesis:Treatment w Nivolumab in combo w Radium-223 is safe in patients w metastatic castrate resistant prostate cancer An overall proportion of subjects w gr3 or higher non-heme adverse events 20% higher than reported in Checkmate-214 trial would be evidence of unacceptable toxicity. In that study the sum of the proportion of subjects w gr3+ non-heme adverse events, attributed to study therapy, was 46%. The null that the rate of gr3+ non-heme toxicity is 46% or less will be tested after every 10 pts and at the end of the trial at the nominal one sided 0.10 significance level. With 36 evaluable subjects there will be at least 87% power to reject the null if the true proportion is 66%. Checkmate-214 is a comparison since the ipilimumab-nivolumab combo represents the immunotherapy combo with the highest frequency of irAEs that is currently FDA approved based on nivolumab 3mg/kg dosing, the dose used in this trial. A toxicity rate higher is not acceptable for further development. |
Safety lead-in evaluation consisting of 6 subjects. The observation period is defined as the time from cycle one day one until the first cycle of nivolumab is completed (from cycle one day one to cycle three day 28). | |
Primary | Phase II: 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 ctNDA 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. |
It is expected that all patients will be accrued within 30 months. | |
Secondary | To assess PSA progression free survival defined by the Prostate Cancer Working Group 3 (PCWG3). | Measurement of clinical activity of nivolumab in combination with Radium-223 in study population. | up to 24 months | |
Secondary | To assess correlation of bone metabolism markers with clinical response. | Measurement of clinical activity of nivolumab in combination with Radium-223 in study population. | between baseline and C4D15 (about 5 months) | |
Secondary | 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). | Measurement of clinical activity of nivolumab in combination with Radium-223 in study population. | up to 24 months | |
Secondary | To assess time to first symptomatic skeletal related event (defined as symptomatic fracture, surgery or radiation to bone, or spinal cord compression). | Measurement of clinical activity of nivolumab in combination with Radium-223 in study population. | up to 24 months | |
Secondary | To assess radiographic progression-free survival as defined by the PCWG3 criteria. | Measurement of clinical activity of nivolumab in combination with Radium-223 in study population. | up to 24 months |
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