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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

Primary Purpose

Castrate-Resistant Prostate Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Atezolizumab
Radium-223 Dichloride
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Castrate-Resistant Prostate Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • City of Hope
  • University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center
  • Yale School of Medicine
  • Georgetown University Medical Center
  • Mayo Clinic Hospital - Florida
  • Indiana University Health Melvin & Bren Simon Cancer Center
  • Tulane University School of Medicine
  • University of Michigan Comprehensive Cancer Center
  • Karmanos Cancer Institute
  • Mayo Clinic - Minnesota
  • Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley
  • Memorial Sloan-Kettering Cancer Center
  • Duke University Hospital
  • Thomas Jefferson University Hospital
  • University of Pittsburgh - Hillman Cancer Center
  • Vanderbilt University Medical Center
  • University of Washington

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1: ATZ + R-223-D (Concurrent)

RT Arm A: ATZ + R-223-D (Concurrent)

RT Arm B: ATZ + R-223-D (Staggered, 28-Day R-223-D Run-In)

RT Arm C: ATZ + R-223-D (Staggered, 28-Day ATZ Run-In)

Cohort 2: ATZ + R-223-D (Staggered, 28-Day R-223-D Run-In)

Cohort 3: ATZ + R-223-D (Staggered, 56-Day R-223-D Run-In)

Arm Description

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Percentage of Participants with Dose-Limiting Toxicities (DLTs)
Percentage of Participants with Adverse Events (AEs)
Percentage of Participants with Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Secondary Outcome Measures

Maximum Observed Serum Concentration (Cmax) of Atezolizumab
Minimum Observed Serum Concentration (Cmin) of Atezolizumab
Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Atezolizumab

Full Information

First Posted
June 20, 2016
Last Updated
September 23, 2019
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT02814669
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
September 23, 2016 (Actual)
Primary Completion Date
July 31, 2019 (Actual)
Study Completion Date
July 31, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Castrate-Resistant Prostate Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1: ATZ + R-223-D (Concurrent)
Arm Type
Experimental
Arm Description
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.
Arm Title
RT Arm A: ATZ + R-223-D (Concurrent)
Arm Type
Experimental
Arm Description
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.
Arm Title
RT Arm B: ATZ + R-223-D (Staggered, 28-Day R-223-D Run-In)
Arm Type
Experimental
Arm Description
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.
Arm Title
RT Arm C: ATZ + R-223-D (Staggered, 28-Day ATZ Run-In)
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 2: ATZ + R-223-D (Staggered, 28-Day R-223-D Run-In)
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 3: ATZ + R-223-D (Staggered, 56-Day R-223-D Run-In)
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Atezolizumab
Other Intervention Name(s)
MPDL3280A
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Radium-223 Dichloride
Other Intervention Name(s)
Xofigo
Intervention Description
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.
Primary Outcome Measure Information:
Title
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)
Title
Percentage of Participants with Adverse Events (AEs)
Time Frame
From Screening to 90 days after the last dose (up to 42 months overall)
Title
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)
Secondary Outcome Measure Information:
Title
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 42 months)
Title
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 42 months)
Title
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 42 months)

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Yale School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Georgetown University Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Mayo Clinic Hospital - Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Indiana University Health Melvin & Bren Simon Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Tulane University School of Medicine
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112-2600
Country
United States
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Mayo Clinic - Minnesota
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Facility Name
Duke University Hospital
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
University of Pittsburgh - Hillman Cancer Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232-1301
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
34108181
Citation
Fong L, Morris MJ, Sartor O, Higano CS, Pagliaro L, Alva A, Appleman LJ, Tan W, Vaishampayan U, Porcu R, Tayama D, Kadel EE 3rd, Yuen KC, Datye A, Armstrong AJ, Petrylak DP. A Phase Ib Study of Atezolizumab with Radium-223 Dichloride in Men with Metastatic Castration-Resistant Prostate Cancer. Clin Cancer Res. 2021 Sep 1;27(17):4746-4756. doi: 10.1158/1078-0432.CCR-21-0063. Epub 2021 Jun 9.
Results Reference
derived

Learn more about this trial

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

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