ISRCTN12669009进行中（未招募）1 期
CUBIC: a Phase I/II study of the CXCR2 inhibitor, AZD5069, in combination with durvalumab (MEDI4736), in patients with advanced hepatocellular carcinoma
HS Greater Glasgow and Clyde0 个研究点目标入组 47 人开始时间: 2022年3月7日最近更新:
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 47
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
入排标准
- 性别
- All
入选标准
- •1. Histologically or cytologically confirmed hepatocellular carcinoma that is not suitable for surgery (with or without transplantation) or locoregional therapies
- •2. Patients with evidence of background liver disease or without evidence of underlying liver disease will be eligible
- •3. Patients who have either (a) not received prior systemic anti-cancer therapy; or (b) who have progressed on, or who are intolerant to, no more than one line or prior therapy with either sorafenib or lenvatinib (patients who change 1st - line tyrosine kinase therapy from sorafenib to lenvatinib, and vice versa, within 2 months of starting treatment because of toxicity, and without evidence of disease progression, will be considered as having had one line of therapy), or an anti-PD(L)-1 antibody either as monotherapy or in combination with bevacizumab, a CTLA-4 antibody, or lenvatinib. Patients who developed > grade 2 immune-mediated toxicity, or who discontinued treatment due to immune-mediated toxicity, or who progressed within the first 12 weeks of previous immunotherapy treatment will be excluded.
- •4. Willing to undergo a pre-treatment biopsy of tumour and of non-tumour liver for pharmacodynamic and predictive biomarker studies
- •5. ECOG performance status =1 (Appendix II)
- •6. Age =18 years
- •7. Measurable disease by RECIST 1.1. Patients who have previously been treated with TACE or ablation will be eligible provided there is either a new measurable lesion (that has not been treated with ablation/TACE) or a new, reproducibly measurable, hyper-vascular area with washout within a previously treated lesion or area
- •8. Estimated life expectancy greater than 3 months
- •9. Adequate haematological function as defined by:
- •9.1. Haemoglobin (Hb) =90 g/l
- •9.2. Neutrophil Count =1.5 x 109 /l
- •9.3. Platelets =75 x 10e9 /l
- •10. Child – Pugh Score A (=6) [Appendix VIII]
- •11. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <3.0 x ULN
- •12. Bilirubin <34 umol/l
- •13. Adequate renal function with creatinine clearance / glomerular filtration rate >50 ml/min as calculated by local standard practice
- •14. Ability to swallow oral medication
- •15. Able to comply with study procedures including on-treatment biopsies of tumour and non-liver tumour in patients recruited into the dose expansion cohorts
- •16. Written informed consent prior to performing any study-related procedures
- •17. Patients with past or ongoing HCV infection will be eligible for the study. Patients who have been treated for HCV infection must have completed their treatment at least 1 month prior to starting trial therapy
- •18. Patients with controlled hepatitis B will be eligible as long as they meet the following criteria:
- •18.1. Antiviral therapy for HBV must be given for at least 4 weeks and HBV viral load must be less than 500 IU/ml prior to the first dose of the study drug. Patients on active HBV therapy with viral loads under 500 IU/ml should stay on the same therapy throughout the study treatment.
- •18.2. Patients who are positive for anti-hepatitis B core antibody HBc, negative for hepatitis B surface antigen (HBsAg), and negative or positive for an
排除标准
- •1. Pregnant or breastfeeding women
- •2. Women of childbearing potential* and men with female partners of childbearing potential who are not willing to use two forms of contraception, including one highly effective method. Men with pregnant or breastfeeding partners should be advised to use barrier method contraception to prevent exposure to the foetus or neonate during treatment.
- •*A woman is considered of childbearing potential (WOCBP) i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
- •3. Cardiovascular disease defined as Stage II to IV congestive heart failure (CHF) as determined by the New York Heart Association (NYHA) classification system, or history of myocardial infarction (MI), or cardiac arrhythmia associated with haemodynamic instability, or unstable angina, or cerebral vascular accident, or transient ischemia, if any have occurred within the previous 12 months prior to study treatment.
- •4. Any other serious medical or psychiatric disorder that would be, in the opinion of the investigator, a contraindication to either the trial procedures or to therapy with AZD5069 or durvalumab
- •5. Patients with a lack of physical integrity of the GI tract leading to a malabsorption syndrome or intestinal obstruction that would impair the administration and absorption of oral therapy
- •6. Any previous > grade 2 toxicity or discontinuation of therapy due to immune-mediated toxicity with an immune checkpoint inhibitor
- •7. Major surgery within 14 days of starting study treatment and patients must have recovered from any effects of major surgery
- •8. Patients with a known hypersensitivity to AZD5069 or durvalumab or any of the excipients of the products
- •9. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
- •9.1. Intranasal, inhaled, or topical steroids; or local steroid injections (e.g., intra-articular injection)
- •9.2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisolone or equivalent
- •9.3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) and chemotherapy-induced nausea and vomiting
- •10. History of allogenic organ transplant
- •11. Active autoimmune disorders, or prior documented severe autoimmune or inflammatory disorders requiring immunosuppressive treatment (including inflammatory bowel disease [e.g., colitis, Crohn’s disease], diverticulitis with the exception of diverticulosis, coeliac disease, irritable bowel syndrome, or other serious gastrointestinal chronic conditions associated with diarrhoea); systemic lupus erythematosus; Wegener syndrome (granulomatosis with polyangiitis), Graves’ disease; rheumatoid arthritis, hypophysitis, uveitis, etc. The following are exceptions to this criterion:
- •11.1. Patients with vitiligo or alopecia
- •11.2. Diabetes mellitus type I or resolved childhood asthma/atopy
- •11.3. Patients with hypothyroidism (e.g., following Hashimot
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