Neoadjuvant Enoblituzumab (MGA271) in Men With Localized Intermediate and High-Risk Prostate Cancer
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|ClinicalTrials.gov Identifier: NCT02923180|
Recruitment Status : Active, not recruiting
First Posted : October 4, 2016
Results First Posted : August 24, 2021
Last Update Posted : December 9, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer||Drug: Enoblituzumab||Phase 2|
This is a single-center, single arm, open-label phase II study evaluating the safety, anti-tumor effect, and immunogenicity of neoadjuvant MGA271 given prior to radical prostatectomy in men with intermediate and high-risk localized prostate cancer. Eligible patients will receive MGA271 at a dose of 15mg/kg IV given weekly for 6 doses beginning 50 days prior to radical prostatectomy. 14 days after the last dose of MGA271, prostate glands will be harvested at the time of radical prostatectomy, and prostate tissue will be examined for the secondary endpoints. Follow-up evaluation for adverse events will occur 30 days and 90 days after surgery. Patients will then be followed by their urologists according to standard institutional practices, but will require PSA evaluations every 3 (±1) months during year 1 and every 6 (±2) months during years 2-3.
In Amendment 1, the study was expanded to enroll an additional 16 patients for a total of 32 patients to continue evaluating safety and better estimate the clinical benefit of Enoblituzumab in terms of undetectable PSA level (<0.1 ng/mL) at 12 months following radical prostatectomy.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||33 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men With Localized Intermediate- and High-Risk Prostate Cancer|
|Actual Study Start Date :||February 14, 2017|
|Actual Primary Completion Date :||August 11, 2020|
|Estimated Study Completion Date :||July 30, 2023|
Men with localized intermediate and high-risk prostate cancer will be given neoadjuvant Enoblituzumab 15mg/kg IV weekly for 6 weeks followed by radical prostatectomy on day 50, with follow-up visits 30 days and 90 days post-prostatectomy. PSA values will be tracked for 3 years post-prostatectomy.
Enoblituzumab 15mg/kg IV (in the vein) weekly for 6 doses beginning 50 days prior to radical prostatectomy.
Other Name: MGA271
- Number of Participants With Treatment-related Adverse Events [ Time Frame: 2 years ]Number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE)v4.0
- Efficacy of Neoadjuvant Enoblituzumab as Assessed by PSA0 Response Rate [ Time Frame: 12 months ]Number of participants with undetectable Prostate Specific Antigen (PSA <0.1 ng/mL) at 12 months following radical prostatectomy
- Quantify Markers of Apoptosis in Prostate Tumor Specimens of Treated Patients [ Time Frame: up to 3 years post-prostatectomy ]Quantify markers of apoptosis in prostate tumor specimens of treated patients using TUNEL staining and expressed as the mean staining percentage in tumor tissue
- Markers of Cell Proliferation [ Time Frame: up to 3 years post-prostatectomy ]Quantify markers of cell proliferation in prostate tumor specimens of treated patients using Ki-67 staining and expressed by the mean staining percentage in tumor tissue
- CD8+ T Cell Infiltration [ Time Frame: up to 3 years post-prostatectomy ]Number of CD8+ T-cells in harvested prostate glands from treated patients
- PD-L1 Expression [ Time Frame: up to 3 years post-prostatectomy ]Mean staining percentage of PD-L1 in tumor tissue, assessed by immunohistochemistry (IHC) in the primary core specimens (pre-treatment) and the prostatectomy surgical specimens (post-treatment).
- Regulatory T Cell (Treg) Infiltration [ Time Frame: up to 3 years post-prostatectomy ]Mean staining percentage of Treg cells in tumor tissue of treated patients, assessed through immunohistochemistry.
- CD4+ T Cell Infiltration [ Time Frame: up to 3 years post-prostatectomy ]Mean staining percentage of CD4+ T-cells in tumor tissue of treated patients, assessed through immunohistochemistry.
- Natural Killer (NK) Cell Density [ Time Frame: up to 3 years post-prostatectomy ]Mean staining percentage of NK cells in harvested prostate glands.
- Enoblituzumab (MGA271) Drug Distribution Evaluated by Detection of MGA271 in Tumor Tissue [ Time Frame: 3 years ]Number of participants with positive or negative MGA271 detection in post-treatment prostate tumor specimens, as evaluated by IHC of fresh frozen sections.
- Pathological Complete Responses (pCR) [ Time Frame: 3 years ]Number of participants who achieve pCR, defined as absence of tumor identification on standard histological analysis of resected prostate specimens.
- PSA Response Rates [ Time Frame: 3 months post-prostatectomy ]Number of participants with undetectable PSA (<0.1 ng/mL) at 3 months after prostatectomy.
- Time to PSA Recurrence [ Time Frame: up to 3 years post-prostatectomy ]Median time from prostatectomy to time when PSA is ≥ 0.2 ng/mL. Estimated using Kaplan-Meier method.
- Gleason Grade Group Change [ Time Frame: Day 50 ]Number of participants with change in Gleason grade group from pre-treatment biopsy vs. post-treatment biopsy. "Downgrade" refers to a net grade group change less than zero, "upgrade" refers to net grade group change more than zero, and "no change" refers to stable Gleason grade group. Gleason grade groups are defined as grade group 1 (Gleason score ≤ 6), grade group 2 (Gleason score 3+4=7), grade group 3 (Gleason score 4+3=7), grade group 4 (Gleason score 8), and grade group 5 (Gleason scores 9-10).The lower the grade group, the better the outcome.
- Number of Participants With PSA Percentage Decrease Prior to Radical Prostatectomy. [ Time Frame: 50 Days ]The PSA percentage change is calculated as the difference from the PSA at day 50 prior to prostatectomy and PSA at screening. A negative value of PSA percentage change ("PSA percentage < 0") indicates a decrease in PSA from screening, and a positive value (PSA percentage change >= 0) indicates an increase in PSA from screening.
- Androgen Receptor (AR) Quantification [ Time Frame: up to 3 years post-prostatectomy ]Mean staining percentage of AR in harvested prostate tissue, assessed by immunohistochemistry (IHC) staining for AR protein.
- Tissue Androgen Concentrations [ Time Frame: up to 3 years post prostatectomy ]Concentration (picogram/3 mg) of testosterone and 5α-dihydrotestosterone (DHT) in prostate tissue.
- Global Expression Profiling of Tumor Tissues [ Time Frame: up to 3 years post-prostatectomy ]Number of participants with changes in cellular composition, upregulation and downregulation of immune checkpoints, and other markers of activity versus exhaustion.
- IHC Analyses of CD137, CD16 and/or CD107A [ Time Frame: up to 3 years post-prostatectomy ]CD137, CD107A, and CD16 expression in prostate tumor specimens will be assessed by immunohistochemistry (IHC) in the prostatectomy surgical specimens (post-treatment). This endpoint will be expressed as the mean staining percentage of each of these in tumor tissue
- TCR Repertoire [ Time Frame: up to 3 years post-prostatectomy ]Number of participants with changes in T-cell receptor (TCR) repertoire, assessed by TCR sequencing.
- FC Receptor Genotyping [ Time Frame: up to 3 years post-prostatectomy ]Number of participants with CD16A, CD32A, and CD32B on Fc receptor.
- PBLs [ Time Frame: up to 3 years post-prostatectomy ]Number of participants with upregulation and downregulation of immune checkpoints and other markers of activity versus exhaustion, as assessed by flow cytometry at treatment day 1 (pre-treatment), treatment day 36 (post-treatment), and 30 days post-prostatectomy.
- B7-H3 Expression [ Time Frame: up to 3 years post-prostatectomy ]B7-H3 expression in prostate tumor specimens will be assessed by IHC (immunohistochemistry) in the primary core specimens (pre-treatment) and in the prostatectomy surgical specimens (post-treatment). This endpoint will be expressed as the mean staining percentage of B7-H3 in tumor tissue.
- PD-1, LAG3, and TIM3 Expression [ Time Frame: up to 3 Years post-prostatectomy ]PD-1, LAG3, and TIM3 expression in prostate tumor specimens will be assessed by IHC (immunohistochemistry) in the primary core specimens (pre-treatment) and in the prostatectomy surgical specimens (post-treatment). This endpoint will be expressed as the mean staining percentage in tumor tissue.
- Quantify Antigen-spread [ Time Frame: up to 3 years post-prostatectomy ]Number of participants with antigen-spread to on-target and off-target antigens.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||Male|
|Accepts Healthy Volunteers:||No|
- Histologically confirmed adenocarcinoma of the prostate (clinical stage T1c-T3b, N0, M0) without involvement of lymph nodes, bone, or visceral organs
- Initial prostate biopsy is available for central pathologic review, and is confirmed to show at least 2 positive cores and a Gleason sum of ≥7
- Radical prostatectomy has been scheduled at Johns Hopkins Hospital
- Age ≥18 years
- ECOG performance status 0-1, or Karnofsky score ≥ 70% (see Appendix A)
Adequate bone marrow, hepatic, and renal function:
- WBC >3,000 cells/mm3
- ANC >1,500 cells/mm3
- Hemoglobin >9.0 g/dL
- Platelet count >100,000 cells/mm3
- Serum creatinine <1.5 × upper limit of normal (ULN)
- Serum bilirubin <1.5 × ULN
- ALT <3 × ULN
- AST <3 × ULN
- Alkaline phosphatase <3 × ULN
- The etiology of abnormal bilirubin and transaminase levels should be evaluated prior to study entry.
- Willingness to provide written informed consent and HIPAA authorization for the release of personal health information, and the ability to comply with the study requirements (note: HIPAA authorization will be included in the informed consent)
- Willingness to use barrier contraception from the time of first dose of MGA271 until the time of prostatectomy.
- Presence of known lymph node involvement or distant metastases
- Other histologic types of prostate cancers such as ductal, sarcomatous, lymphoma, small cell, and neuroendocrine tumors
- Prior radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for prostate cancer
- Prior immunotherapy/vaccine therapy for prostate cancer
- Prior use of experimental agents for prostate cancer
- Concomitant treatment with other hormonal therapy or 5α-reductase inhibitors
- Current use of systemic corticosteroids or use of systemic corticosteroids within 4 weeks of enrollment (inhaled corticosteroids for asthma or COPD are permitted as are other non-systemic steroids such as topical corticosteroids)
- History or presence of autoimmune disease requiring systemic immunosuppression (including but not limited to: inflammatory bowel disease, systemic lupus erythematosus, vasculitis, rheumatoid arthritis, scleroderma, multiple sclerosis, hemolytic anemia, Sjögren syndrome, and sarcoidosis)
- History of malignancy within the last 3 years, with the exception of non-melanoma skin cancers and superficial bladder cancer
- Uncontrolled major active infectious, cardiovascular, pulmonary, hematologic, or psychiatric illnesses that would make the patient a poor study candidate
- Known prior or current history of HIV and/or hepatitis B/C
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): NCT02923180
|United States, Maryland|
|Johns Hopkins Sidney Kimmel Comprehensive Cancer Center|
|Baltimore, Maryland, United States, 21205|
|Principal Investigator:||Emmanuel Antonarakis, MD||Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
Documents provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
|Responsible Party:||Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Other Study ID Numbers:||
IRB00103776 ( Other Identifier: JHM IRB )
|First Posted:||October 4, 2016 Key Record Dates|
|Results First Posted:||August 24, 2021|
|Last Update Posted:||December 9, 2022|
|Last Verified:||December 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
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