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

Overview

About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location	Status	Contact
Jacksonville, Fla. Mayo Clinic principal investigator Winston Tan, M.D.	Closed for enrollment	Contact information: Cancer Center Clinical Trials Referral Office 855-776-0015
Rochester, Minn. Mayo Clinic principal investigator Lance Pagliaro, M.D.	Closed for enrollment	Contact information: Cancer Center Clinical Trials Referral Office (855) 776-0015

Mayo Clinic Location

Status

Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Winston Tan, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Lance Pagliaro, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

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