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Trial record 3 of 25 for:    alpharadin | Open Studies

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2017 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02814669
First received: June 20, 2016
Last updated: February 22, 2017
Last verified: February 2017
  Purpose
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. An adaptive design is planned to first investigate the tolerability with concurrent administration (both treatments to begin in Cycle 1). However, if the combination is not tolerated, additional cohorts may be enrolled to evaluate the tolerability of radium-223 dichloride (to begin in Cycle 1) with delayed atezolizumab (to begin in Cycle 2 and/or 3).

Condition Intervention Phase
Castrate-Resistant Prostate Cancer
Drug: Atezolizumab
Drug: Radium-223 dichloride
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of participants with dose-limiting toxicities (DLTs) [ Time Frame: From Day 1 to Day 28 of Cycle 1 (cycle length is 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 per Prostate Cancer Working Group 2 (PCWG2), loss of clinical benefit, withdrawal, death, or study end (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 on Day 1 of atezolizumab Cycle 1; pre-dose (0 hours) on Day 1 of atezolizumab Cycles 2, 3, 4, 8; at treatment discontinuation (up to 36 months); 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 on Day 1 of atezolizumab Cycle 1; pre-dose (0 hours) on Day 1 of atezolizumab Cycles 2, 3, 4, 8; at treatment discontinuation (up to 36 months); 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 Cycles 1, 2, 3, 4, 8 containing atezolizumab; at treatment discontinuation (up to 36 months); and 120 days after last atezolizumab dose (up to 36 months) ]

Estimated Enrollment: 45
Study Start Date: September 2016
Estimated Study Completion Date: August 2019
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 may be randomized to compare concurrent versus staggered administration of atezolizumab and radium-223 dichloride for the full treatment period (anticipated up to 36 months).
Drug: Atezolizumab
Atezolizumab will be given as 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 as 50 kilobecquerels per kilogram (kBq/kg) via slow IV bolus on Day 1 of each 28-day cycle for up to 6 treatments.
Experimental: Cohort 2: ATZ + R-223-D (Staggered, 28-Day Run-In)
If the combination tested in Cohort 1 is not tolerated, radium-223 dichloride will begin during Cycle 1 and atezolizumab will be delayed to begin 28 days later in Cycle 2. If tolerability is favorable during the 28-day DLT assessment in Cycle 2, additional participants may receive the same staggered administration of atezolizumab and radium-223 dichloride for the full treatment period (anticipated up to 36 months).
Drug: Atezolizumab
Atezolizumab will be given as 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 as 50 kilobecquerels per kilogram (kBq/kg) via slow IV bolus on Day 1 of each 28-day cycle for up to 6 treatments.
Experimental: Cohort 3: ATZ + R-223-D (Staggered, 56-Day Run-In)
If the combination tested in Cohort 2 is not tolerated, radium-223 dichloride will begin during Cycle 1 and atezolizumab will be further delayed to begin 56 days later in Cycle 3. If tolerability is favorable during the 28-day DLT assessment in Cycle 3, additional participants may receive the same staggered administration of atezolizumab and radium-223 dichloride for the full treatment period (anticipated up to 36 months).
Drug: Atezolizumab
Atezolizumab will be given as 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 as 50 kilobecquerels per kilogram (kBq/kg) via slow IV bolus on Day 1 of each 28-day cycle for up to 6 treatments.

  Eligibility

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

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
  • Life expectancy >/=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
  • Visceral metastasis (excluding liver metastases) and/or lymphadenopathy >/=2 centimeters (cm) in short-axis diameter
  • Tumors that are amenable to serial biopsy
  • Disease progression according to PCWG2 criteria during or following treatment with an androgen pathway inhibitor (i.e., 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 within 3 weeks of study drug
  • Anti-androgen therapy within 6 weeks prior to study drug
  • Participation in another clinical trial/investigation within 28 days prior to study drug
  • Eligible for treatment with docetaxel, unless docetaxel was declined after an informed decision
  • Prior chemotherapy for treatment of CRPC, except when docetaxel has been given for hormone-sensitive prostate cancer
  • Brain metastases or active leptomeningeal disease
  • Uncontrolled tumor-related pain
  • Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
  • 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 cluster of differentiation (CD) 137 agonist, anti-programmed death (PD) 1, or anti-programmed death ligand (PD-L) 1 therapeutic antibody
  • 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 study drug
  • Spinal compression or pathologic fractures
  • Bone marrow dysplasia
  • Unmanageable fecal incontinence
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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 Recruiting
Duarte, California, United States, 91010
University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center Not yet 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 Not yet recruiting
Washington, District of Columbia, United States, 20007
United States, Florida
Mayo Clinic Hospital - Florida Not yet 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 Not yet 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 Not yet recruiting
Rochester, Minnesota, United States, 55905
United States, Nevada
Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley Recruiting
Las Vegas, Nevada, United States, 89169
United States, New York
Memorial Sloan-Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
United States, North Carolina
Duke University Hospital Not yet 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 Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15232-1301
United States, Tennessee
Vanderbilt University Medical Center Not yet recruiting
Nashville, Tennessee, United States, 37232
United States, Washington
University of Washington Not yet 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 
Study First Received: June 20, 2016
Last Updated: February 22, 2017

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

ClinicalTrials.gov processed this record on February 24, 2017