Clinical trial NCT02923180: Neoadjuvant Enoblituzumab (MGA271) in Men With Localized Intermediate and High-Risk Prostate Cancer
Official title: A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men With Localized Intermediate- and High-Risk Prostate Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: enobilituzumab
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: MacroGenics
First posted: 2016-10-04
Enrollment: 33
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study evaluates the safety, anti-tumor effect, and immunogenicity of Enoblituzumab given before radical prostatectomy. All patients will receive Enoblituzumab for 6 weekly doses beginning 50 days prior to radical prostatectomy.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of Participants With Treatment-related Adverse Events
timeFrame: 2 years
measure: Efficacy of Neoadjuvant Enoblituzumab as Assessed by PSA0 Response Rate
timeFrame: 12 months
Secondary outcomes:
measure: Quantify Markers of Apoptosis in Prostate Tumor Specimens of Treated Patients
timeFrame: up to 5 years post-prostatectomy
measure: Mean Staining Percentage of Markers of Cell Proliferation
timeFrame: 3 years post-prostatectomy
measure: CD8+ T Cell Infiltration
timeFrame: 3 years post-prostatectomy
measure: PD-L1 Expression
timeFrame: 3 years post-prostatectomy
measure: Regulatory T Cell (Treg) Infiltration
timeFrame: 3 years post-prostatectomy
measure: CD4+ T Cell Infiltration
timeFrame: 3 years post-prostatectomy
measure: Natural Killer (NK) Cell Density
timeFrame: 3 years post-prostatectomy
measure: Enoblituzumab (MGA271) Drug Distribution Evaluated by Detection of MGA271 in Tumor Tissue
timeFrame: 3 years
measure: Pathological Complete Responses (pCR)
timeFrame: 3 years
measure: PSA Response Rates
timeFrame: 3 months post-prostatectomy
measure: Time to PSA Recurrence
timeFrame: up to 37 months post-prostatectomy
measure: Gleason Grade Group Change
timeFrame: Day 50
measure: Number of Participants With PSA Percentage Decrease Prior to Radical Prostatectomy.
timeFrame: 50 Days
Other outcomes:
measure: Androgen Receptor (AR) Quantification
timeFrame: up to 3 years post-prostatectomy
measure: Tissue Androgen Concentrations
timeFrame: up to 3 years post prostatectomy
measure: Global Expression Profiling of Tumor Tissues
timeFrame: up to 3 years post-prostatectomy
measure: IHC Analyses of CD137, CD16 and/or CD107A
timeFrame: up to 3 years post-prostatectomy
measure: TCR Repertoire
timeFrame: 3 years post-prostatectomy
measure: FC Receptor Genotyping
timeFrame: up to 3 years post-prostatectomy
measure: PBLs
timeFrame: 3 years post-prostatectomy
measure: B7-H3 Expression
timeFrame: 3 years post-prostatectomy
measure: PD-1, LAG3, and TIM3 Expression
timeFrame: 3 Years post-prostatectomy
measure: Quantify Antigen-spread
timeFrame: 3 years post-prostatectomy
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Eugene Shenderov, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: