A Phase Ib, Open-Label Study of the Safety and Tolerability of Atezolizumab in Combination With Radium-223 Dichloride in Patients With Castrate-Resistant Prostate Cancer Who Have Progressed Following Treatment With an Androgen Pathway Inhibitor
Overview
- Phase
- Phase 1
- Intervention
- Atezolizumab
- Conditions
- Castrate-Resistant Prostate Cancer
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 45
- Locations
- 17
- Primary Endpoint
- Percentage of Participants with Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
Eligibility Criteria
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
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
Arms & Interventions
Cohort 1: ATZ + R-223-D (Concurrent)
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.
Intervention: Atezolizumab
Cohort 1: ATZ + R-223-D (Concurrent)
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.
Intervention: Radium-223 Dichloride
RT Arm A: ATZ + R-223-D (Concurrent)
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.
Intervention: Atezolizumab
RT Arm A: ATZ + R-223-D (Concurrent)
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.
Intervention: Radium-223 Dichloride
RT Arm B: ATZ + R-223-D (Staggered, 28-Day R-223-D Run-In)
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.
Intervention: Atezolizumab
RT Arm B: ATZ + R-223-D (Staggered, 28-Day R-223-D Run-In)
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.
Intervention: Radium-223 Dichloride
RT Arm C: ATZ + R-223-D (Staggered, 28-Day ATZ Run-In)
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.
Intervention: Atezolizumab
RT Arm C: ATZ + R-223-D (Staggered, 28-Day ATZ Run-In)
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.
Intervention: Radium-223 Dichloride
Cohort 2: ATZ + R-223-D (Staggered, 28-Day R-223-D Run-In)
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.
Intervention: Atezolizumab
Cohort 2: ATZ + R-223-D (Staggered, 28-Day R-223-D Run-In)
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.
Intervention: Radium-223 Dichloride
Cohort 3: ATZ + R-223-D (Staggered, 56-Day R-223-D Run-In)
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.
Intervention: Atezolizumab
Cohort 3: ATZ + R-223-D (Staggered, 56-Day R-223-D Run-In)
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.
Intervention: Radium-223 Dichloride
Outcomes
Primary Outcomes
Percentage of Participants with Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Time Frame: 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)
Time Frame: 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)
Time Frame: From Screening to 90 days after the last dose (up to 42 months overall)
Secondary Outcomes
- 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))