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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ClinicalTrials.gov Identifier: NCT02814669

Recruitment Status : Recruiting

First Posted : June 28, 2016

Last Update Posted : May 8, 2018

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Sponsor:

Information provided by (Responsible Party):

Hoffmann-La Roche

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
Castrate-Resistant Prostate Cancer	Drug: Atezolizumab Drug: Radium-223 Dichloride	Phase 1

Study Design


Study Type :	Interventional (Clinical Trial)
Estimated 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 :	September 23, 2016
Estimated Primary Completion Date :	March 31, 2020
Estimated Study Completion Date :	March 31, 2020

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Prostate cancer

MedlinePlus related topics: Prostate Cancer

Drug Information available for: Radium Ra 223 dichloride Atezolizumab

U.S. FDA Resources

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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Xofigo

Outcome Measures

Primary Outcome Measures :

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) ]
Percentage of Participants with Adverse Events (AEs) [ Time Frame: From Screening to 90 days after the last dose (up to 36 months overall) ]
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 36 months overall) ]

Secondary Outcome Measures :

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) ]
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) ]
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) ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	Male
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02814669

Contacts


Contact: Reference Study ID Number: BO30013 www.roche.com/about_roche/roche_worldwide.htm	888-662-6728 (U.S. and Canada)	global-roche-genentech-trials@gene.com

Locations


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

Sponsors and Collaborators

Hoffmann-La Roche

Investigators


Study Director:	Clinical Trials	Hoffmann-La Roche

More Information


Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT02814669 History of Changes
Other Study ID Numbers:	BO30013 2015-003606-17 ( EudraCT Number )
First Posted:	June 28, 2016 Key Record Dates
Last Update Posted:	May 8, 2018
Last Verified:	May 2018

Additional relevant MeSH terms:


Prostatic Neoplasms Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Neoplasms Genital Diseases, Male Prostatic Diseases Androgens	Atezolizumab Radium Ra 223 dichloride Antibodies, Monoclonal Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antineoplastic Agents Immunologic Factors

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