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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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT02814669
Collaborator
(none)
45
Enrollment
17
Locations
6
Arms
34.2
Actual Duration (Months)
2.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
45 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Sep 23, 2016
Actual Primary Completion Date :
Jul 31, 2019
Actual Study Completion Date :
Jul 31, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: Atezolizumab
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.
Other Names:
  • MPDL3280A

    • Drug: Radium-223 Dichloride
    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.
    Other Names:
  • Xofigo

    		•
    Experimental: 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.

    Drug: Atezolizumab
    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.
    Other Names:
  • MPDL3280A

    • Drug: Radium-223 Dichloride
    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.
    Other Names:
  • Xofigo

    		•
    Experimental: 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.

    Drug: Atezolizumab
    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.
    Other Names:
  • MPDL3280A

    • Drug: Radium-223 Dichloride
    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.
    Other Names:
  • Xofigo

    		•
    Experimental: 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.

    Drug: Atezolizumab
    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.
    Other Names:
  • MPDL3280A

    • Drug: Radium-223 Dichloride
    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.
    Other Names:
  • Xofigo

    		•
    Experimental: 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.

    Drug: Atezolizumab
    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.
    Other Names:
  • MPDL3280A

    • Drug: Radium-223 Dichloride
    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.
    Other Names:
  • Xofigo

    		•
    Experimental: 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.

    Drug: Atezolizumab
    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.
    Other Names:
  • MPDL3280A

    • Drug: Radium-223 Dichloride
    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.
    Other Names:
  • Xofigo

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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)]

    2. Percentage of Participants with Adverse Events (AEs) [From Screening to 90 days after the last dose (up to 42 months overall)]

    3. 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 Outcome Measures

    1. 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)]

    2. 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)]

    3. 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)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope Duarte California United States 91010
    2 University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center San Francisco California United States 94158
    3 Yale School of Medicine New Haven Connecticut United States 06510
    4 Georgetown University Medical Center Washington District of Columbia United States 20007
    5 Mayo Clinic Hospital - Florida Jacksonville Florida United States 32224
    6 Indiana University Health Melvin & Bren Simon Cancer Center Indianapolis Indiana United States 46202
    7 Tulane University School of Medicine New Orleans Louisiana United States 70112-2600
    8 University of Michigan Comprehensive Cancer Center Ann Arbor Michigan United States 48109
    9 Karmanos Cancer Institute Detroit Michigan United States 48201
    10 Mayo Clinic - Minnesota Rochester Minnesota United States 55905
    11 Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley Las Vegas Nevada United States 89169
    12 Memorial Sloan-Kettering Cancer Center Commack New York United States 11725
    13 Duke University Hospital Durham North Carolina United States 27710
    14 Thomas Jefferson University Hospital Philadelphia Pennsylvania United States 19107
    15 University of Pittsburgh - Hillman Cancer Center Pittsburgh Pennsylvania United States 15232-1301
    16 Vanderbilt University Medical Center Nashville Tennessee United States 37232
    17 University of Washington Seattle Washington United States 98195

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT02814669
    Other Study ID Numbers:
    • BO30013
    • 2015-003606-17
    First Posted:
    Jun 28, 2016
    Last Update Posted:
    Sep 24, 2019
    Last Verified:
    Sep 1, 2019
    Additional relevant MeSH terms:
    Prostatic Neoplasms
    Atezolizumab
    Radium Ra 223 dichloride

    Study Results

    No Results Posted as of Sep 24, 2019