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

NCT ID: NCT02814669

Last Updated: 2019-09-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-23
• Study Completion Date: 2019-07-31

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.

Conditions

Castrate-Resistant Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

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.

Radium-223 Dichloride

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

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.

Radium-223 Dichloride

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

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.

Radium-223 Dichloride

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

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.

Radium-223 Dichloride

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

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.

Radium-223 Dichloride

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

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.

Radium-223 Dichloride

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

MPDL3280A; Xofigo

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

City of Hope

Duarte, California, United States

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

San Francisco, California, United States

Yale School of Medicine

New Haven, Connecticut, United States

Georgetown University Medical Center

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

Mayo Clinic Hospital - Florida

Jacksonville, Florida, United States

Indiana University Health Melvin & Bren Simon Cancer Center

Indianapolis, Indiana, United States

Tulane University School of Medicine

New Orleans, Louisiana, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Mayo Clinic - Minnesota

Rochester, Minnesota, United States

Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley

Las Vegas, Nevada, United States

Memorial Sloan-Kettering Cancer Center

Commack, New York, United States

Duke University Hospital

Durham, North Carolina, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

University of Pittsburgh - Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

University of Washington

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34108181 (View on PubMed)

Other Identifiers

2015-003606-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BO30013

Identifier Type: -

Identifier Source: org_study_id