Castrate-Resistant Prostate Cancer
Conditions
Brief summary
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.
Interventions
DRUGAtezolizumab
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.
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.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Life expectancy greater than or equal to (\>/=) 12 weeks * Histologically confirmed, castrate-resistant adenocarcinoma of the prostate * Measurable disease according to RECIST v1.1 * Multiple bone metastases within 12 weeks prior to study drug * Participants receiving bisphosphonate or denosumab therapy must have been on a stable dose for at least 4 weeks * Visceral metastasis and/or lymphadenopathy * Tumors that are amenable to serial biopsy * Disease progression according to Prostate Cancer Working Group 2 (PCWG2) criteria during or following treatment with at least one second generation androgen pathway inhibitor (for example, enzalutamide, abiraterone) for metastatic prostate cancer * Adequate hematologic and end-organ function * One prior taxane-containing regimen for mCRPC, or refusal or ineligibility of a taxane-containing regimen
Exclusion criteria
* History of small-cell or neuroendocrine prostate carcinoma * Treatment with approved anti-cancer therapy (with the exception of abiraterone) within 3 weeks of study drug. Abiraterone must not be administered within 2 weeks prior to initiation of study treatment * Participation in another clinical trial/investigation within 28 days prior to study drug * Brain metastases or active leptomeningeal disease (with the exception of participants with treated epidural disease and no other epidural progression) * Uncontrolled tumor-related pain * Uncontrolled hypercalcemia * Significant cardiovascular disease * History of autoimmune disease except controlled/treated hypothyroidism, type 1 diabetes mellitus, or certain skin disorders * Prior allogeneic stem cell or solid organ transplant * History of pulmonary fibrosis/inflammation, including active tuberculosis * Human immunodeficiency virus (HIV) or hepatitis B or C * Prior treatment with cluster of differentiation (CD) 137 agonist, anti-programmed death (PD) 1, or anti-programmed death ligand (PD-L) 1 therapeutic antibody or pathway-targeting agents * Immunostimulants within 4 weeks or immunosuppressants within 14 days prior to study drug * Prior radium-223 dichloride or hemibody external radiotherapy * Systemic strontium-89, samarium-153, rhenium-186, or rhenium-188 for bone metastases within 24 weeks prior to initiation of study treatment * Spinal compression or structurally unstable bone lesions suggesting impending pathologic fractures based on clinical findings and/or magnetic resonance imaging (MRI) * Bone marrow dysplasia * Unmanageable fecal incontinence
Design outcomes
Primary
| Measure | 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) |
Secondary
| Measure | 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 | 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) |
Countries
United States
Outcome results
None listed