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


Condition: Castrate-Resistant Prostate Cancer

Intervention:

  • Drug: Atezolizumab
  • Drug: Radium-223 Dichloride

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. 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.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02814669

Sponsor: Hoffmann-La Roche

Primary Outcome Measures:

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

Secondary Outcome Measures:

  • Measure: 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)
  • Safety Issue:
  • Measure: 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)
  • Safety Issue:
  • Measure: 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)
  • Safety Issue:

Estimated Enrollment: 45

Study Start Date: September 23, 2016

Phase: Phase 1

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

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

Contact:

  • Reference Study ID Number: BO30013 www.roche.com/about_roche/roche_worldwide.htm
  • 888-662-6728 (U.S. and Canada)

Locations:

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

View trial on ClinicalTrials.gov