Neoadjuvant Atezolizumab With or Without Enzalutamide in Localized Prostate Cancer Given Before Radical Prostatectomy
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|ClinicalTrials.gov Identifier: NCT03821246|
Recruitment Status : Recruiting
First Posted : January 29, 2019
Last Update Posted : November 20, 2019
|Condition or disease||Intervention/treatment||Phase|
|Prostate Adenocarcinoma||Drug: Atezolizumab Drug: Enzalutamide||Phase 2|
I. To determine the impact of atezolizumab-based combination therapy on the composition and function of tumor-infiltrating immune cells (TIICS).
I. To determine the safety and tolerability of atezolizumab-based combination therapy in localized prostate cancer (PC).
II. To determine the clinical efficacy of atezolizumab-based combination therapy in localized PC.
I. To characterize changes in the frequency and number of circulating immune cells following atezolizumab-based combination therapy in localized PC.
II. To determine the impact of atezolizumab-based combination therapy on the composition and phenotype of the tumor microenvironment.
III. To determine the impact of atezolizumab-based combination therapy on the circulating and intratumoral T cell repertoire.
IV. To explore the role of novel imaging modalities to understand the immunologic and clinical impact to immunotherapeutic approaches in localized PC.
V. To characterize changes in the gut microbiome associated with each therapeutic combination.
OUTLINE: Patients are assigned sequentially to 1 of 2 groups.
COHORT A: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1.
COHORT B: Patients receive atezolizumab as in Cohort A and enzalutamide orally (PO) once daily (QD) on days 1-21.
Two more groups consisting of treatment with atezolizumab in combination with other drugs may be added in the future.
In all cohorts, treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Beginning 28 days after treatment, patients undergo radical prostatectomy.
After completion of study treatment, patients are followed up at 14 days, 6 and 12 weeks, and 6 and 12 months.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||51 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-Label Multi-Center Phase II Study of Neoadjuvant Atezolizumab-Based Combination Therapy in Men With Localized Prostate Cancer Prior to Radical Prostatectomy|
|Actual Study Start Date :||January 25, 2019|
|Estimated Primary Completion Date :||September 2021|
|Estimated Study Completion Date :||January 2022|
Experimental: Cohort A (atezolizumab)
Patients receive atezolizumab intravenously IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Beginning 28 days after treatment, patients undergo radical prostatectomy.
Experimental: Cohort B (atezolizumab, enzalutamide)
Patients receive atezolizumab as in Cohort A and enzalutamide PO QD on days 1-21. Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Beginning 28 days after treatment, patients undergo radical prostatectomy.
- Changes in tumor-infiltrating effector cluster of differentiation 3 (CD3)+ T cells by multiplexed immunohistochemistry (IHC) [ Time Frame: Baseline up to 12 months ]The proportion of subjects with positive responses will be reported with 95% confidence intervals.
- Incidence of adverse events per National Institutes of Health (NIH) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [ Time Frame: Up to 12 months ]Adverse events will be tabulated.
- Pathologic complete response (pCR) rate [ Time Frame: Up to 12 months ]Defined as defined as the absence of tumor on the gross specimen.Will be reported following standard pathologic review of the radical prostatectomy (RP) specimen. These will be reported in sum [pCR+ minimal residual disease (MRD) rate] and independently.
- MRD rate [ Time Frame: Up to 12 months ]Defined as the sum of the cross-sectional diameter of residual tumors =< 0.5 cm. Will be reported following standard pathologic review of the RP specimen. These will be reported in sum (pCR+MRD rate) and independently.
- Prostate specific antigen (PSA) response [ Time Frame: Up to 2 months ]Defined as >= 50% decline in PSA. The PSA response proportion will be reported for each cohort.
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): NCT03821246
|Contact: Lawrence Fong, MD||415-514-3160||Lawrence.Fong@ucsf.edu|
|Contact: Andy Chon||415-476-2351||Andrew.Chon@ucsf.edu|
|United States, California|
|University of California, San Francisco||Recruiting|
|San Francisco, California, United States, 94143|
|Contact: Lawrence Fong, MD 415-514-3160 Lawrence.Fong@ucsf.edu|
|Contact: Andy Chon 415-476-2351 Andrew.Chon@ucsf.edu|
|Principal Investigator: Lawrence Fong, MD|
|United States, Missouri|
|Siteman Cancer Center at Washington University||Not yet recruiting|
|Saint Louis, Missouri, United States, 63110|
|Contact: Russell K. Pachynski 314-286-2341 email@example.com|
|Principal Investigator: Russell K. Pachynski|
|Principal Investigator:||Lawrence Fong, MD||University of California, San Francisco|