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
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| ClinicalTrials.gov Identifier: NCT02814669 |
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Recruitment Status :
Completed
First Posted : June 28, 2016
Last Update Posted : September 24, 2019
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Sponsor:
Hoffmann-La Roche
Information provided by (Responsible Party):
Hoffmann-La Roche
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Castrate-Resistant Prostate Cancer | Drug: Atezolizumab Drug: Radium-223 Dichloride | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 45 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | September 23, 2016 |
| Actual Primary Completion Date : | July 31, 2019 |
| Actual Study Completion Date : | July 31, 2019 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Prostate cancer
MedlinePlus related topics:
Prostate Cancer
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Cohort 1: ATZ + R-223-D (Concurrent)
Participants 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.
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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.
Other Name: MPDL3280A Drug: 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.
Other Name: Xofigo |
|
Experimental: RT Arm A: ATZ + R-223-D (Concurrent)
If 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.
|
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.
Other Name: MPDL3280A Drug: 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.
Other Name: Xofigo |
|
Experimental: RT Arm B: ATZ + R-223-D (Staggered, 28-Day R-223-D Run-In)
If 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.
|
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.
Other Name: MPDL3280A Drug: 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.
Other Name: Xofigo |
|
Experimental: RT Arm C: ATZ + R-223-D (Staggered, 28-Day ATZ Run-In)
If 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.
|
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.
Other Name: MPDL3280A Drug: 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.
Other Name: Xofigo |
|
Experimental: Cohort 2: ATZ + R-223-D (Staggered, 28-Day R-223-D Run-In)
If 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.
|
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.
Other Name: MPDL3280A Drug: 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.
Other Name: Xofigo |
|
Experimental: Cohort 3: ATZ + R-223-D (Staggered, 56-Day R-223-D Run-In)
If 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.
|
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.
Other Name: MPDL3280A Drug: 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.
Other Name: Xofigo |
Primary Outcome Measures :
- 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) ]
- Percentage of Participants with Adverse Events (AEs) [ Time Frame: From Screening to 90 days after the last dose (up to 42 months overall) ]
- 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 42 months overall) ]
Secondary Outcome Measures :
- 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 42 months) ]
- 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 42 months) ]
- 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 42 months) ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Male |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02814669
Locations
| United States, California | |
| City of Hope | |
| Duarte, California, United States, 91010 | |
| University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center | |
| San Francisco, California, United States, 94158 | |
| United States, Connecticut | |
| Yale School of Medicine | |
| New Haven, Connecticut, United States, 06510 | |
| United States, District of Columbia | |
| Georgetown University Medical Center | |
| Washington, District of Columbia, United States, 20007 | |
| United States, Florida | |
| Mayo Clinic Hospital - Florida | |
| Jacksonville, Florida, United States, 32224 | |
| United States, Indiana | |
| Indiana University Health Melvin & Bren Simon Cancer Center | |
| Indianapolis, Indiana, United States, 46202 | |
| United States, Louisiana | |
| Tulane University School of Medicine | |
| New Orleans, Louisiana, United States, 70112-2600 | |
| United States, Michigan | |
| University of Michigan Comprehensive Cancer Center | |
| Ann Arbor, Michigan, United States, 48109 | |
| Karmanos Cancer Institute | |
| Detroit, Michigan, United States, 48201 | |
| United States, Minnesota | |
| Mayo Clinic - Minnesota | |
| Rochester, Minnesota, United States, 55905 | |
| United States, Nevada | |
| Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley | |
| Las Vegas, Nevada, United States, 89169 | |
| United States, New York | |
| Memorial Sloan-Kettering Cancer Center | |
| Commack, New York, United States, 11725 | |
| United States, North Carolina | |
| Duke University Hospital | |
| Durham, North Carolina, United States, 27710 | |
| United States, Pennsylvania | |
| Thomas Jefferson University Hospital | |
| Philadelphia, Pennsylvania, United States, 19107 | |
| University of Pittsburgh - Hillman Cancer Center | |
| Pittsburgh, Pennsylvania, United States, 15232-1301 | |
| United States, Tennessee | |
| Vanderbilt University Medical Center | |
| Nashville, Tennessee, United States, 37232 | |
| United States, Washington | |
| University of Washington | |
| Seattle, Washington, United States, 98195 | |
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
| Study Director: | Clinical Trials | Hoffmann-La Roche |
| Responsible Party: | Hoffmann-La Roche |
| ClinicalTrials.gov Identifier: | NCT02814669 History of Changes |
| Other Study ID Numbers: |
BO30013 2015-003606-17 ( EudraCT Number ) |
| First Posted: | June 28, 2016 Key Record Dates |
| Last Update Posted: | September 24, 2019 |
| Last Verified: | September 2019 |
Additional relevant MeSH terms:
|
Prostatic Neoplasms Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Neoplasms Genital Diseases, Male Prostatic Diseases Atezolizumab |
Radium Ra 223 dichloride Antibodies, Monoclonal Androgens Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs Hormones Hormones, Hormone Substitutes, and Hormone Antagonists |