An Open Label Phase II Study of the Efficacy and Tolerability of PRL3-ZUMAB and Predictive Biomarkers in Advanced Solid Tumours
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 14
- 试验地点
- 2
- 主要终点
- Objective response rate
研究概览
简要总结
This is a Phase II, open-label, single dose level study of PRL3-ZUMAB monotherapy in patients with advanced solid tumours that have failed standard therapy. Approximately 30 patients will be recruited with ~10 gastric cancers and ~10 hepatocellular carcinomas. Patients who have received at least 1 dose of PRL3-ZUMAB will be evaluable for toxicity and efficacy.
PRL3-ZUMAB will be given IV every 2 weeks for up to 12 infusions in the absence of unmanageable toxicities or disease progression. Patients who are benefitting from the treatment may continue on PRL3-ZUMAB beyond 12 infusions with the agreement of the study drug provider.
PRL3-ZUMAB at the RP2D in tumour types enriched for known PRL-3 expression for efficacy and tolerability will be evaluated. There will also be in depth molecular profiling of tissues in patients who have an objective response or prolonged disease stabilization to identify predictive/selection biomarkers as well as evaluation of the oncogenic signaling modulation and immunomodulation by PRL3-ZUMAB and its potential for future combination with other targeted therapies or immunotherapy.
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
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients 21 years of age or older at the time written informed consent is obtained.
- •Histopathological- or cytological- documented advanced curatively unresectable solid tumors failing standard therapy.
- •For HCC must have failed at least 1 line of standard therapy.
- •For gastric cancer must have failed at least 2 line of standard therapy (inclusive of adjuvant treatment).
- •For other solid tumours must have failed at least 1 line of standard therapy.
- •Progressive disease following the last treatment
- •Life expectancy ≥ 4 months
- •Eastern Cooperative Oncology Group (ECOG) performance status (ECOG PS) score of ≤ 2 at study entry
- •Recovery to Grade ≤ 1 by the Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE v 4.03), from the effects of recent surgery, radiotherapy, chemotherapy, hormonal therapy, or other targeted therapies for cancer, with the exception of non-clinically significant adverse events such as alopecia; biochemical abnormalities, or resolved to Grade ≤ 2: peripheral neuropathy; hypertension and proteinuria.
- •Women of childbearing potential (WOCBP) must have a negative pregnancy test at study entry. Subjects not considered WOCBP are those without menses for 24 consecutive months, and those who have undergone hysterectomy and/or bilateral salpingo-oophorectomy. WOCBP must be willing to use acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, or condom with spermicide, or abstinence) for the duration of the study.
- •Adequate organ and hematological function as evidenced by the following laboratory studies within 10 days of 1st treatment:
- •Absolute neutrophil count ≥ 1.0 x 10^9/L.
- •Platelet count ≥ 75 x 10^9/L. Hemoglobin ≥ 9 g/dL.
- •Prothrombin time and activated partial thromboplastin time ≤ 1.5 x upper limit of normal (ULN) per institutional laboratory normal range.
- •Total bilirubin ≤ 1.5x ULN.
- •Aspartate aminotransferase and alanine aminotransferase ≤ 3 x ULN (≤ 5x ULN in the presence of liver mets).
- •For patients with hepatocellular carcinoma (HCC) Child Pugh score of ≤ B
- •Creatinine < 1.5x ULN
- •Evaluable or measurable disease by RECIST v1.1
- •Patients with active Hepatitis B (defined as Hep B S Ag or DNA positive) need to be on anti-viral therapy while on PRL3-ZUMAB.
排除标准
- •Untreated or symptomatic central nervous system metastases. Patients with treated brain metastases stable for 3 months are eligible to enroll.
- •Major surgical procedures within 28 days prior to enrolment.
- •Pregnant or breast-feeding females.
- •Known HIV infection.
- •Treatment with any of the following anti-cancer therapies prior to the first dose of study drugs within the stated time frames:
- •Prior chemotherapy ≤ 2 weeks of C1 Day 1 of PRL3-ZUMAB.
- •Biological therapy (e.g., antibodies) within a period of time that is ≤ 5 t1/2 or ≤ 3 weeks, whichever is shorter, prior to starting study drug.
- •Continuous or intermittent small molecule therapeutics within a period of time that is ≤ 5 t1/2 or ≤ 3 weeks (whichever is shorter) prior to starting study drug.
- •Any other investigational agents within a period of time that is ≤ 5 t1/2 or less than the cycle length used for that treatment or ≤ 4 weeks (whichever is shortest) prior to starting study drug.
- •Wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug.
- •Patients requiring regular immunosuppressive medication for autoimmune disease or corticosteroid doses of >10mg prednisolone for greater than 2 days
- •Unable to provide informed consent.
- •History of another cancer within the last 2 years, with the exception of
- •Curatively resected non-melanomatous skin cancer,
- •Curatively treated cervical carcinoma in-situ,
- •Prostate cancer treated with leuteinizing hormone-releasing hormone (LH-RH) agonists/pure antagonists for at least 2 months
- •Prior stem cell or bone marrow transplant
- •Vaccinated within 2 weeks from prior to the first administration of PRL3-ZUMAB
研究组 & 干预措施
PRL3-ZUMAB Monotherapy
干预措施: PRL3-zumab (Drug)
结局指标
主要结局
Objective response rate
时间窗: From start of treatment to first occurence of disease progression or death, up to 2 years
Number of patients that do not have disease progression at 16 weeks from start of treatment
时间窗: 16 weeks after start of treatment
Clinical benefit rate at 16 weeks
Treatment related adverse events rate
时间窗: From start of treatment to 30 days after last dose of study drug
次要结局
未报告次要终点