Clinical trial NCT02814669: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Castrate-Resistant Prostate Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-06-28
Enrollment: 45
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Percentage of Participants with Dose-Limiting Toxicities (DLTs)
timeFrame: Days 1-28 of Cycle 1 (for Cohort 1), Cycle 2 (for Cohort 2), and Cycle 3 (for Cohort 3) (Cycle length = 28 days)
measure: Percentage of Participants with Adverse Events (AEs)
timeFrame: From Screening to 90 days after the last dose (up to 42 months overall)
measure: Percentage of Participants with Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
timeFrame: 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 outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of Atezolizumab
timeFrame: 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)
measure: Minimum Observed Serum Concentration (Cmin) of Atezolizumab
timeFrame: 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)
measure: Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
timeFrame: 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)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center
state: California
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic Hospital - Florida
state: Florida
city: Indianapolis
country: United States
facility: Indiana University Health Melvin & Bren Simon Cancer Center
state: Indiana
city: New Orleans
country: United States
facility: Tulane University School of Medicine
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - Minnesota
state: Minnesota
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley
state: Nevada
city: Commack
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh - Hillman Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Fong L, Morris MJ, Sartor O, Higano CS, Pagliaro L, Alva A, Appleman LJ, Tan W, Vaishampayan U, Porcu R, Tayama D, Kadel EE 3rd, Yuen KC, Datye A, Armstrong AJ, Petrylak DP. A Phase Ib Study of Atezolizumab with Radium-223 Dichloride in Men with Metastatic Castration-Resistant Prostate Cancer. Clin Cancer Res. 2021 Sep 1;27(17):4746-4756. doi: 10.1158/1078-0432.CCR-21-0063. Epub 2021 Jun 9.