Clinical Trials /

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

NCT02814669

Description:

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.

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: BO30013
  • SECONDARY ID: 2015-003606-17
  • NCT ID: NCT02814669

Conditions

  • Castrate-Resistant Prostate Cancer

Interventions

DrugSynonymsArms
AtezolizumabMPDL3280ACohort 1: ATZ + R-223-D (Concurrent)
Radium-223 DichlorideXofigoCohort 1: ATZ + R-223-D (Concurrent)

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Cohort 1: ATZ + R-223-D (Concurrent)ExperimentalParticipants 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.
  • Atezolizumab
  • Radium-223 Dichloride
RT Arm A: ATZ + R-223-D (Concurrent)ExperimentalIf 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.
  • Atezolizumab
  • Radium-223 Dichloride
RT Arm B: ATZ + R-223-D (Staggered, 28-Day R-223-D Run-In)ExperimentalIf 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.
  • Atezolizumab
  • Radium-223 Dichloride
RT Arm C: ATZ + R-223-D (Staggered, 28-Day ATZ Run-In)ExperimentalIf 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.
  • Atezolizumab
  • Radium-223 Dichloride
Cohort 2: ATZ + R-223-D (Staggered, 28-Day R-223-D Run-In)ExperimentalIf 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.
  • Atezolizumab
  • Radium-223 Dichloride
Cohort 3: ATZ + R-223-D (Staggered, 56-Day R-223-D Run-In)ExperimentalIf 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.
  • Atezolizumab
  • Radium-223 Dichloride

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 (excluding liver metastases) 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 an androgen pathway inhibitor (that is,
             enzalutamide, abiraterone) for metastatic CRPC

          -  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

          -  Eligible for treatment with a taxane-containing regimen (for example, docetaxel),
             unless taxane-containing regimen was declined after an informed decision

          -  Prior chemotherapy (for example, docetaxel, cabazitaxel) for treatment of CRPC, except
             when docetaxel has been given for hormone-sensitive prostate cancer

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Maximum Observed Serum Concentration (Cmax) of Atezolizumab
Time Frame: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 36 months)
Safety Issue:
Description:
Measure:Minimum Observed Serum Concentration (Cmin) of Atezolizumab
Time Frame: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 36 months)
Safety Issue:
Description:
Measure:Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
Time Frame: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 36 months)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

September 7, 2017