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Castrate-Resistant Prostate CancerPhase 1NCT02814669

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

A Phase 1 study testing Atezolizumab and Radium-223 Dichloride in people with Castrate-Resistant Prostate Cancer, run by Hoffmann-La Roche at 17 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Castrate-Resistant Prostate Cancer
What is being tested?
Atezolizumab and Radium-223 Dichloride
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
17 sitesUnited States
Study dates
23 Sep 2016to 31 Jul 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

United States17 sites

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • Memorial Sloan-Kettering Cancer Center

    Commack, New York, 11725

  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • City of Hope

    Duarte, California, 91010

  • Duke University Hospital

    Durham, North Carolina, 27710

  • Indiana University Health Melvin & Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Mayo Clinic Hospital - Florida

    Jacksonville, Florida, 32224

  • Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley

    Las Vegas, Nevada, 89169

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Yale School of Medicine

    New Haven, Connecticut, 06510

  • Tulane University School of Medicine

    New Orleans, Louisiana, 70112-2600

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • University of Pittsburgh - Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232-1301

  • Mayo Clinic - Minnesota

    Rochester, Minnesota, 55905

  • University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center

    San Francisco, California, 94158

  • University of Washington

    Seattle, Washington, 98195

  • Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

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

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.

Being tested
Atezolizumab, Radium-223 Dichloride

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabDrug

    Also called MPDL3280A

    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 DichlorideDrug

    Also called Xofigo

    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.

Study groups in NCT02814669
Study groupRoleWhat they receive
Cohort 1: ATZ + R-223-D (Concurrent)ExperimentalParticipants 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 will be randomized to Arms A, B, and C.
Receives: Drug: Atezolizumab; Drug: Radium-223 Dichloride
RT Arm A: ATZ + R-223-D (Concurrent)ExperimentalIf Cohort 1 regimen is found to be safe, additional participants will be randomized to this arm (randomized treatment [RT]) to receive concurrent radium-223 dichloride and atezolizumab.
Receives: Drug: Atezolizumab; Drug: Radium-223 Dichloride
RT Arm B: ATZ + R-223-D (Staggered, 28-Day R-223-D Run-In)ExperimentalIf Cohort 1 regimen is found to be safe, additional participants will be randomized to this arm to receive radium-223 dichloride in Cycle 1 and radium-223 dichloride and atezolizumab from Cycle 2 onward.
Receives: Drug: Atezolizumab; Drug: Radium-223 Dichloride
RT Arm C: ATZ + R-223-D (Staggered, 28-Day ATZ Run-In)ExperimentalIf Cohort 1 regimen is found to be safe, additional participants will be randomized to this arm to receive atezolizumab in Cycle 1 and radium-223 dichloride and atezolizumab from Cycle 2 onward.
Receives: Drug: Atezolizumab; Drug: Radium-223 Dichloride
Cohort 2: ATZ + R-223-D (Staggered, 28-Day R-223-D Run-In)ExperimentalIf Cohort 1 regimen is not tolerable, Arms A, B, and C will not be introduced and additional participants will be enrolled in this cohort to receive radium-223 dichloride in Cycle 1 and radium-223 dichloride and atezolizumab in Cycle 2. If the regimen is found to be safe, additional participants will be enrolled to receive this same treatment (radium-223 dichloride in Cycle 1 and radium-223 dichloride and atezolizumab from Cycle 2 onward). If, at Cycle 2, Cohort 2 regiment is not tolerable, additional participants will be enrolled in Cohort 3.
Receives: Drug: Atezolizumab; Drug: Radium-223 Dichloride
Cohort 3: ATZ + R-223-D (Staggered, 56-Day R-223-D Run-In)ExperimentalIf Cohort 2 regimen is not tolerable, additional participants will be enrolled in this cohort to receive radium-223 dichloride in Cycles 1, 2 and radium-223 dichloride and atezolizumab in Cycle 3. If the regimen is found to be safe, additional participants will be enrolled to receive this same treatment (radium-223 dichloride in Cycles 1, 2 and radium-223 dichloride and atezolizumab from Cycle 3 onward). If, at Cycle 3, Cohort 3 regiment is not tolerable, no additional participants will be enrolled in this study.
Receives: Drug: Atezolizumab; Drug: Radium-223 Dichloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants with Dose-Limiting Toxicities (DLTs)

    Measured: Days 1-28 of Cycle 1 (for Cohort 1), Cycle 2 (for Cohort 2), and Cycle 3 (for Cohort 3) (Cycle length = 28 days)

  2. Percentage of Participants with Adverse Events (AEs)

    Measured: From Screening to 90 days after the last dose (up to 42 months overall)

  3. Percentage of Participants with Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

    Measured: 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 (3)

  1. Maximum Observed Serum Concentration (Cmax) of Atezolizumab

    Measured: 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)

  2. Minimum Observed Serum Concentration (Cmin) of Atezolizumab

    Measured: 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)

  3. Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Atezolizumab

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jun 2016 (estimated)
  2. Study start23 Sep 2016
  3. Primary completion31 Jul 2019
  4. Study completion31 Jul 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02814669
Sponsor's protocol ID
BO30013
Other IDs
2015-003606-17, 2015
Status last verified
Sep 2019
First submitted
20 Jun 2016
Last updated
24 Sep 2019
Results posted
No

Publications

  • 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.

    PubMed 34108181

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Atezolizumab and Radium-223 Dichloride in people with Castrate-Resistant Prostate Cancer, run by Hoffmann-La Roche at 17 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02814669, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2019.

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