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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-003606-17 | EudraCT Number |
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This study is designed to assess the safety and tolerability of atezolizumab when given in combination with radium-223 dichloride in participants with metastatic CRPC who have progressed after treatment with an androgen pathway inhibitor. This adaptive design study includes a cohort phase and a potential randomization phase. An initial concurrent dosing evaluation will evaluate the safety and tolerability of a treatment regimen that employs a concurrent start time for atezolizumab and radium-223 dichloride (Cohort 1). If concurrent dosing is found to be safe and tolerable in Cohort 1, additional participants will be enrolled and eligible participants will be randomized in a 1:1:1 ratio to Arms A, B, and C. If concurrent dosing is not tolerated in Cohort 1, new participants will be enrolled in a staggered dosing evaluation: Cohort 2 (28-day radium-223 dichloride run-in, atezolizumab will begin on Day 1 of Cycle 2) and Cohort 3 (56-day radium-223 dichloride run-in, atezolizumab will begin on Day 1 of Cycle 3). If the Cohort 2 schedule is tolerable, then additional participants will be enrolled using this treatment schedule; If the Cohort 2 schedule is not tolerable, subsequent participants will be enrolled in Cohort 3. If the Cohort 3 schedule is tolerable, then additional participants will be enrolled using this treatment schedule. If Cohort 3 schedule is not tolerable, no additional participant will be enrolled in the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: ATZ + R-223-D (Concurrent) | Experimental | Participants will receive concurrent radium-223 dichloride and atezolizumab for a single-cycle, 28-day dose limiting toxicity (DLT) assessment. If the combination is initially found to be safe and tolerable, additional participants will be randomized to Arms A, B, and C. |
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| RT Arm A: ATZ + R-223-D (Concurrent) | Experimental | If Cohort 1 regimen is found to be safe, additional participants will be randomized to this arm (randomized treatment [RT]) to receive concurrent radium-223 dichloride and atezolizumab. |
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| RT Arm B: ATZ + R-223-D (Staggered, 28-Day R-223-D Run-In) | Experimental | If Cohort 1 regimen is found to be safe, additional participants will be randomized to this arm to receive radium-223 dichloride in Cycle 1 and radium-223 dichloride and atezolizumab from Cycle 2 onward. |
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| RT Arm C: ATZ + R-223-D (Staggered, 28-Day ATZ Run-In) | Experimental | If Cohort 1 regimen is found to be safe, additional participants will be randomized to this arm to receive atezolizumab in Cycle 1 and radium-223 dichloride and atezolizumab from Cycle 2 onward. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atezolizumab | Drug | Atezolizumab will be given at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or disease progression. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants with Dose-Limiting Toxicities (DLTs) | Days 1-28 of Cycle 1 (for Cohort 1), Cycle 2 (for Cohort 2), and Cycle 3 (for Cohort 3) (Cycle length = 28 days) | |
| Percentage of Participants with Adverse Events (AEs) | From Screening to 90 days after the last dose (up to 42 months overall) | |
| Percentage of Participants with Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | From Baseline until disease progression, death, loss to follow-up, withdrawal of consent, or study termination by the Sponsor, whichever occurs first (up to 42 months overall) |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Serum Concentration (Cmax) of Atezolizumab | Pre-dose (0 hours) and 30 minutes post-dose (infusion length=60 minutes) on Day 1 of atezolizumab Cycle 1; pre-dose on Day 1 of atezolizumab Cycles 2, 3, 4, 8; at Treatment discontinuation and 120 days after last atezolizumab dose (up to 42 months) | |
| Minimum Observed Serum Concentration (Cmin) of Atezolizumab |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| City of Hope | Duarte | California | 91010 | United States | ||
| University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34108181 | Derived | Fong L, Morris MJ, Sartor O, Higano CS, Pagliaro L, Alva A, Appleman LJ, Tan W, Vaishampayan U, Porcu R, Tayama D, Kadel EE 3rd, Yuen KC, Datye A, Armstrong AJ, Petrylak DP. A Phase Ib Study of Atezolizumab with Radium-223 Dichloride in Men with Metastatic Castration-Resistant Prostate Cancer. Clin Cancer Res. 2021 Sep 1;27(17):4746-4756. doi: 10.1158/1078-0432.CCR-21-0063. Epub 2021 Jun 9. |
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| Cohort 2: ATZ + R-223-D (Staggered, 28-Day R-223-D Run-In) | Experimental | If Cohort 1 regimen is not tolerable, Arms A, B, and C will not be introduced and additional participants will be enrolled in this cohort to receive radium-223 dichloride in Cycle 1 and radium-223 dichloride and atezolizumab in Cycle 2. If the regimen is found to be safe, additional participants will be enrolled to receive this same treatment (radium-223 dichloride in Cycle 1 and radium-223 dichloride and atezolizumab from Cycle 2 onward). If, at Cycle 2, Cohort 2 regiment is not tolerable, additional participants will be enrolled in Cohort 3. |
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| Cohort 3: ATZ + R-223-D (Staggered, 56-Day R-223-D Run-In) | Experimental | If Cohort 2 regimen is not tolerable, additional participants will be enrolled in this cohort to receive radium-223 dichloride in Cycles 1, 2 and radium-223 dichloride and atezolizumab in Cycle 3. If the regimen is found to be safe, additional participants will be enrolled to receive this same treatment (radium-223 dichloride in Cycles 1, 2 and radium-223 dichloride and atezolizumab from Cycle 3 onward). If, at Cycle 3, Cohort 3 regiment is not tolerable, no additional participants will be enrolled in this study. |
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| Radium-223 Dichloride | Drug | Radium-223 dichloride will be administered at a dose of 55 kilobecquerels per kilogram (kBq/kg) via slow IV bolus on Day 1 of each 28-day cycle for up to 6 cycles. |
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| Pre-dose (0 hours) and 30 minutes post-dose (infusion length=60 minutes) on Day 1 of atezolizumab Cycle 1; pre-dose on Day 1 of atezolizumab Cycles 2, 3, 4, 8; at Treatment discontinuation and 120 days after last atezolizumab dose (up to 42 months) |
| Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Atezolizumab | Pre-dose (0 hours) on Day 1 of atezolizumab Cycles 1, 2, 3, 4, 8; at treatment discontinuation (up to 36 months); and 120 days after last atezolizumab dose (up to 42 months) |
| San Francisco |
| California |
| 94158 |
| United States |
| Yale School of Medicine | New Haven | Connecticut | 06510 | United States |
| Georgetown University Medical Center | Washington D.C. | District of Columbia | 20007 | United States |
| Mayo Clinic Hospital - Florida | Jacksonville | Florida | 32224 | United States |
| Indiana University Health Melvin & Bren Simon Cancer Center | Indianapolis | Indiana | 46202 | United States |
| Tulane University School of Medicine | New Orleans | Louisiana | 70112-2600 | United States |
| University of Michigan Comprehensive Cancer Center | Ann Arbor | Michigan | 48109 | United States |
| Karmanos Cancer Institute | Detroit | Michigan | 48201 | United States |
| Mayo Clinic - Minnesota | Rochester | Minnesota | 55905 | United States |
| Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley | Las Vegas | Nevada | 89169 | United States |
| Memorial Sloan-Kettering Cancer Center | Commack | New York | 11725 | United States |
| Duke University Hospital | Durham | North Carolina | 27710 | United States |
| Thomas Jefferson University Hospital | Philadelphia | Pennsylvania | 19107 | United States |
| University of Pittsburgh - Hillman Cancer Center | Pittsburgh | Pennsylvania | 15232-1301 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
| University of Washington | Seattle | Washington | 98195 | United States |
| ID | Term |
|---|---|
| C000594389 | atezolizumab |
| C581106 | radium Ra 223 dichloride |
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