A Phase 2 Randomized Trial of Neoadjuvant Enoblituzumab Versus Standard of Care in Men With High-Risk Localized Prostate Cancer: The Help Elucidate & Attack Longitudinally (HEAT) Prostate Cancer Randomized Study
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 219
- 试验地点
- 8
- 主要终点
- Recurrence-free survival (RFS)
研究概览
简要总结
This study evaluates the efficacy, anti-tumor effect, and immunogenicity of neoadjuvant enoblituzumab given before radical prostatectomy. Patients will be randomized to enoblituzumab for a total of 12 weeks beginning 84 days before radical prostatectomy or standard of care arms.
详细描述
This is a multi-center, randomized, phase 2 study evaluating the efficacy, anti-tumor effect, and immunogenicity of neoadjuvant enoblituzumab given prior to radical prostatectomy in men with high-risk localized prostate cancer. Patients will be recruited from the outpatient Urology clinics and Multidisciplinary Prostate Cancer ("Precision Medicine") Clinics at four participating institutions including: Harvard/Dana-Farber Cancer Centers, Northwestern Lurie Comprehensive Cancer Center, Mayo Clinic, and the University of Minnesota Masonic Cancer Center. Eligible patients will undergo a pre-treatment prostate biopsy and conventional imaging (CT and bone scan) as well as PSMA-PET and optional prostate MRI as per institutional preferences. Patients who have N0 M0 disease by conventional imaging (N1 by PSMA allowed with up to 3 LNs each ≤1 cm) will be trial eligible as long as concurrent hormonal or radiation therapy is not given. Patients will then be randomized to enoblituzumab for a total of 12 weeks beginning 84 days prior to radical prostatectomy or SOC arms. Fourteen days after the last treatment, prostate glands will be harvested at radical prostatectomy, and prostate tissue will be examined for pathologic response and secondary pharmacodynamic/immunologic endpoints as described herein. Pre-treatment, on-treatment, and post-treatment biomarkers of response and resistance will be collected including: plasma, PBMC. Repeat PSMA scan will be obtained prior to radical prostatectomy. Follow-up evaluation for adverse events will occur 30 and 90 days after surgery. Patients will then be followed by the patient's urologists/oncologists 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •To be eligible for this study, patients must meet all of the following criteria:
- •Histologically confirmed adenocarcinoma of the prostate (clinical stage T1c-T3b, N0, M0) without involvement of lymph nodes, bone, or visceral organs by CT or NM bone scan. N1 by PSMA allowed with up to 3 LNs each ≤1 cm. If there is no frank bone disease, but PSMA scan and CT scan are in discordance, then investigators will discuss.
- •Initial prostate biopsy, obtained within 3 months of enrollment, is available for central pathologic review, and is confirmed to show at least 3 positive cores (at least 1 core with at least 50% disease involvement with ≥4+3=7 disease) and a Gleason sum of ≥8 (or 4+3=7 with at least 1 additional high-risk feature such as PSA>20 or cT3)
- •Radical prostatectomy has been scheduled
- •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 Enoblituzumab (MGA271) until the time of prostatectomy.
排除标准
- •To be eligible for this study, patients should not meet any of the following criteria:
- •Presence of known lymph node involvement on CT (N1 by PSMA allowed with up to 3 LNs each ≤1 cm) or distant metastases by CT and NM bone scan
- •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, with the exception of patients who have been successfully treated for hepatitis B/C (i.e. documented confirmation of cure at least 6 months after initial treatment).
研究组 & 干预措施
Enoblituzumab
Men with localized intermediate and high-risk prostate cancer will be given neoadjuvant Enoblituzumab 15mg/kg IV every 2 weeks for 12 weeks, followed by a radical prostatectomy on day 84, with follow-up visits 30 days, 90 days, 6 months, and 9 months post-prostatectomy. PSA values will be tracked for 3 years post-prostatectomy.
干预措施: Enoblituzumab (Drug)
Standard of Care
Patients will undergo standard of care radical prostatectomy within 4-8 weeks of randomization.
干预措施: Standard of Care (Other)
结局指标
主要结局
Recurrence-free survival (RFS)
时间窗: 3 years post-prostatectomy
Number of participants with RFS, defined as from randomization to any metastasis events, pelvic lymph node recurrence, detectable prostate-specific antigen (PSA) (PSA \>= 0.2 ng/mL, confirmed by a second PSA of the same level or higher), or start of salvage or adjuvant therapy based on PSA criteria of 0.1 ng/mL or higher, or death for any cause, whichever occurs first.
次要结局
- Overall survival(5 years post-prostatectomy)
- Metastasis-free survival(5 years post-prostatectomy)
- Recurrence free survival(3 years from randomization)
- Time to PSA recurrence(5 years post-prostatectomy)
- PSA response(3 months post-prostatectomy.)
- Assess the immune response (CD8 Granzyme B) to enoblituzumab versus SOC(Day 84)
- Pathological complete responses (pCR)(Day 84)
- Number of participants with treatment-related adverse events(90 days post-prostatectomy)
- Assess the immune response (CD8 T cell infiltration into the tumor / peritumoral area) to enoblituzumab versus SOC(Day 84)
- Change in number of participants with change in Gleason grade group change(Baseline and Day 84)
- Anti-tumor response (cleaved PARP staining and quantification of tumor cell apoptosis) to enoblituzumab versus SOC(Day 84)
- Anti-tumor response (central pathological response graded according to standard criteria) to enoblituzumab versus SOC(Day 84)