A Phase 1b Trial Investigating Docetaxel Combined with Cirmtuzumab in Patients with Metastatic Castration Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Recommended phase 2 dose of docetaxel combined with cirmtuzumab
研究概览
简要总结
The purpose of this study is to examine the safety and efficacy of cirmtuzumab in combination with standard of care docetaxel in patients with metastatic castration resistant prostate cancer. Docetaxel is a taxane chemotherapy which has been shown to prolong survival in men with castration resistant prostate cancer. Cirmtuzumab is a monoclonal antibody that targets the receptor called ROR1 of the non-canonical Wnt pathway and is suspected to contribute to prostate cancer growth and progression.
详细描述
This study seeks to targeting the non-canonical Wnt pathway with an antibody against ROR1. ROR1 is an attractive target given its low expression in non-malignant tissues and its role in proliferation and survival in prostate cancer. From preclinical data in a variety of tumor types, blockade of ROR1 inhibits cell growth and cirmtuzumab has shown efficacy in clinical trials with CLL. Preclinical data suggests that ROR1 is upregulated in chemotherapy resistant cells and treatment with cirmtuzumab and a taxane achieved higher cytotoxic response than both agents alone, supporting the use of the combination of cirmtuzumab and a taxane. Based on the biological rationale behind cirmtuzumab and preclinical activity with docetaxel, this is an open label, phase 2 clinical trial to evaluate the safety and efficacy of cirmtuzumab in combination with docetaxel for the treatment of metastatic, castrate resistant prostate adenocarcinoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Participants must have histologically or cytologically confirmed adenocarcinoma of the prostate. Patients with neuroendocrine component are eligible.
- •Participants must have castrate levels of serum testosterone < 50 ng/dL.
- •Participants without orchiectomy must be maintained on luteinizing hormone releasing hormone (LHRH) agonist/antagonist.
- •Participants must have received prior abiraterone and/or next generation androgen receptor antagonist (enzalutamide, apalutamide, or darolutamide) for hormone sensitive disease or CRPC. Prior docetaxel for hormone sensitive disease is permitted.
- •Participants must have progressive disease. Patients with non-measurable disease are eligible.
- •Eastern Cooperative Oncology Group performance status ≤1 (Karnofsky ≥80%).
- •Patients must have normal organ and marrow function.
排除标准
- •No pure small cell carcinoma.
- •Prior treatment with cirmtuzumab.
- •No prior treatment with docetaxel for CRPC.
- •Treatment with abiraterone, apalutamide, or darolutamide within 2 weeks of treatment initiation. Treatment with cytotoxic chemotherapy within 3 weeks of treatment initiation. Treatment enzalutamide or other investigational prostate cancer directed therapy within 4 weeks of treatment initiation.
- •Palliative radiation therapy to the bone or other sites within 2 weeks of treatment initiation.
- •Imminent or established spinal cord compression based on clinical and/or imaging findings.
- •Known active central nervous system metastases and/or carcinomatous meningitis.
- •Uncontrolled intercurrent illness or clinically significant medical condition.
- •Treatment with antimicrobial agent within 4 weeks of treatment initiation.
研究组 & 干预措施
Cirmtuzumab + Docetaxel
There is only one treatment arm on this study. The combination of cirmtuzumab + docetaxel will be administered on one treatment arm. Treatment will cirmtuzumab will be administered initially as a loading dose alone on days 1, 15, and 29 of cycle 1. Following the loading, cirmtuzumab will be given on Day 1 of every 21-day cycle starting on Cycle 2 to up to Cycle 7 corresponding with concurrent docetaxel administration. Following discontinuation or completion of docetaxel, treatment with cirmtuzumab will be continued Day 1 of every 28 cycle until disease progression, toxicity or study withdrawal. Docetaxel will be administered on day 1 of every 21-day cycle starting Cycle 2 for up to 6 cycles.
干预措施: Cirmtuzumab (Drug)
结局指标
主要结局
Recommended phase 2 dose of docetaxel combined with cirmtuzumab
时间窗: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months
Defined by CTCAE version 5 grading
次要结局
- Incidence of treatment-emergent adverse events(Patients will be followed from study entry to death or date last known alive, assessed up to 36 months)
- Time to increase in the total alkaline phosphatase level(Patients will be followed from study entry to death or date last known alive, assessed up to 36 months)
- Composite clinical benefit(Patients will be followed from study entry to death or date last known alive, assessed up to 36 months)
- Total alkaline phosphatase response(Patients will be followed from study entry to death or date last known alive, assessed up to 36 months)
- Time to first subsequent anti-cancer therapy(Patients will be followed from study entry to death or date last known alive, assessed up to 36 months)
- Radiographic progression free survival(Patients will be followed from study entry to death or date last known alive, assessed up to 36 months)
- Time to PSA progression(Patients will be followed from study entry to death or date last known alive, assessed up to 36 months)
- Time to first symptomatic skeletal event(Patients will be followed from study entry to death or date last known alive, assessed up to 36 months)
- Overall survival(Patients will be followed from study entry to death or date last known alive, assessed up to 36 months)
研究者
Rana Mckay
Associate Professor of Medicine and Urology
University of California, San Diego