Safety and Tolerability of Atezolizumab (ATZ) in Combination With Radium-223 Dichloride (R-223-D) in Metastatic Castrate-Resistant Prostate Cancer (CRPC) Progressed Following Treatment With an Androgen Pathway Inhibitor
- Conditions
- Castrate-Resistant Prostate Cancer
- Interventions
- Registration Number
- NCT02814669
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 45
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description RT Arm B: ATZ + R-223-D (Staggered, 28-Day R-223-D Run-In) Atezolizumab 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. RT Arm C: ATZ + R-223-D (Staggered, 28-Day ATZ Run-In) Radium-223 Dichloride 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. Cohort 1: ATZ + R-223-D (Concurrent) Atezolizumab 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. RT Arm A: ATZ + R-223-D (Concurrent) Atezolizumab 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. RT Arm C: ATZ + R-223-D (Staggered, 28-Day ATZ Run-In) Atezolizumab 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. Cohort 2: ATZ + R-223-D (Staggered, 28-Day R-223-D Run-In) Atezolizumab 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. Cohort 3: ATZ + R-223-D (Staggered, 56-Day R-223-D Run-In) Atezolizumab 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. Cohort 1: ATZ + R-223-D (Concurrent) Radium-223 Dichloride 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. RT Arm A: ATZ + R-223-D (Concurrent) Radium-223 Dichloride 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. RT Arm B: ATZ + R-223-D (Staggered, 28-Day R-223-D Run-In) Radium-223 Dichloride 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. Cohort 2: ATZ + R-223-D (Staggered, 28-Day R-223-D Run-In) Radium-223 Dichloride 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. Cohort 3: ATZ + R-223-D (Staggered, 56-Day R-223-D Run-In) Radium-223 Dichloride 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.
- Primary Outcome Measures
Name Time Method 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) 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)
- Secondary Outcome Measures
Name Time Method 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) 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) 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)
Trial Locations
- Locations (17)
Mayo Clinic - Minnesota
🇺🇸Rochester, Minnesota, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸Commack, New York, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Mayo Clinic Hospital - Florida
🇺🇸Jacksonville, Florida, United States
Duke University Hospital
🇺🇸Durham, North Carolina, United States
Tulane University School of Medicine
🇺🇸New Orleans, Louisiana, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Indiana University Health Melvin & Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
University of Pittsburgh - Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
University of Washington
🇺🇸Seattle, Washington, United States
Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley
🇺🇸Las Vegas, Nevada, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
City of Hope
🇺🇸Duarte, California, United States
Yale School of Medicine
🇺🇸New Haven, Connecticut, United States
University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States