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

Castrate-Resistant Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02814669
• Other study ID #: BO30013
• Secondary ID: 2015-003606-17
• Status: Completed
• Phase: Phase 1
• Start date: September 23, 2016
• Est. completion date: July 31, 2019

Study information

• Verified date: September 2019
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: July 31, 2019
• Est. primary completion date: July 31, 2019
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Castrate-Resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Memorial Sloan-Kettering Cancer Center	Commack	New York
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Duke University Hospital	Durham	North Carolina
United States	Indiana University Health Melvin & Bren Simon Cancer Center	Indianapolis	Indiana
United States	Mayo Clinic Hospital - Florida	Jacksonville	Florida
United States	Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley	Las Vegas	Nevada
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale School of Medicine	New Haven	Connecticut
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pittsburgh - Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Mayo Clinic - Minnesota	Rochester	Minnesota
United States	University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	University of Washington	Seattle	Washington
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Dose-Limiting Toxicities (DLTs)		Days 1-28 of Cycle 1 (for Cohort 1), Cycle 2 (for Cohort 2), and Cycle 3 (for Cohort 3) (Cycle length = 28 days)
Primary	Percentage of Participants with Adverse Events (AEs)		From Screening to 90 days after the last dose (up to 42 months overall)
Primary	Percentage of Participants with Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)		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	Maximum Observed Serum Concentration (Cmax) of Atezolizumab		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)
Secondary	Minimum Observed Serum Concentration (Cmin) of Atezolizumab		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)
Secondary	Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Atezolizumab		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)