NCT02814669

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
45

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Sep 2016

Typical duration for phase_1

Geographic Reach
1 country

17 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 20, 2016

Completed
8 days until next milestone

First Posted

Study publicly available on registry

June 28, 2016

Completed
3 months until next milestone

Study Start

First participant enrolled

September 23, 2016

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 31, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2019

Completed
Last Updated

September 24, 2019

Status Verified

September 1, 2019

Enrollment Period

2.9 years

First QC Date

June 20, 2016

Last Update Submit

September 23, 2019

Conditions

Castrate-Resistant Prostate Cancer

Outcome Measures

Primary Outcomes (3)

  • 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)

  • 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 Outcomes (3)

  • 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)

  • 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)

  • 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)

Study Arms (6)

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

EXPERIMENTAL

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: AtezolizumabDrug: Radium-223 Dichloride

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

EXPERIMENTAL

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: AtezolizumabDrug: Radium-223 Dichloride

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

EXPERIMENTAL

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: AtezolizumabDrug: Radium-223 Dichloride

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

EXPERIMENTAL

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: AtezolizumabDrug: Radium-223 Dichloride

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

EXPERIMENTAL

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: AtezolizumabDrug: Radium-223 Dichloride

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

EXPERIMENTAL

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: AtezolizumabDrug: Radium-223 Dichloride

Interventions

AtezolizumabDRUG

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.

Also known as: MPDL3280A
Cohort 1: ATZ + R-223-D (Concurrent)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)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)
Radium-223 DichlorideDRUG

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.

Also known as: Xofigo
Cohort 1: ATZ + R-223-D (Concurrent)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)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)

Eligibility Criteria

Age18 Years+
Sexmale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (17)

City of Hope

Duarte, California, 91010, United States

Location

University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06510, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Mayo Clinic Hospital - Florida

Jacksonville, Florida, 32224, United States

Location

Indiana University Health Melvin & Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Tulane University School of Medicine

New Orleans, Louisiana, 70112-2600, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic - Minnesota

Rochester, Minnesota, 55905, United States

Location

Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley

Las Vegas, Nevada, 89169, United States

Location

Memorial Sloan-Kettering Cancer Center

Commack, New York, 11725, United States

Location

Duke University Hospital

Durham, North Carolina, 27710, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh - Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232-1301, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Related Publications (1)

  • 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.

    PMID: 34108181DERIVED

MeSH Terms

Interventions

atezolizumabradium Ra 223 dichloride

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 20, 2016

First Posted

June 28, 2016

Study Start

September 23, 2016

Primary Completion

July 31, 2019

Study Completion

July 31, 2019

Last Updated

September 24, 2019

Record last verified: 2019-09

Locations

US(17)