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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

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ClinicalTrials.gov Identifier: NCT02814669
Recruitment Status : Active, not recruiting
First Posted : June 28, 2016
Last Update Posted : December 11, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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 Type : Interventional  (Clinical Trial)
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 : 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

MedlinePlus related topics: Prostate Cancer

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




Primary Outcome Measures :
  1. 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) ]
  2. Percentage of Participants with Adverse Events (AEs) [ Time Frame: 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) [ 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 Measures :
  1. 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) ]
  2. 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) ]
  3. 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) ]


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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 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

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


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

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: December 11, 2018
Last Verified: December 2018

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