EUCTR2017-002468-41-DE进行中（未招募）1 期
A phase I/II multicenter, open-label Study of DKN-01 to investigate the anti-tumor activity and safety of DKN-01 in Patients with Hepatocellular Carcinoma and WNT signaling Alterations - DKN-01 inhibition in advanced liver cancer
niversity Medical Center of the Johannes Gutenberg- University Mainz0 个研究点目标入组 70 人开始时间: 2017年12月13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
- 70
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •Patients meeting all of the following criteria will be considered for enrollment to the trial:
- •-Ambulatory male or female patients = 18 years
- •-Patients must have histologically confirmed diagnosis
- •-Tumor tissue is mandatory for pre-treatment evaluation (baseline) (fresh biopsy during
- •4-weeks screening time preferred. Archived specimen is only acceptable, if = 6 months
- •old. Baseline tumor biopsy samples must be available prior to the first dose of DKN-01.
- •-Tumor tissue (FFPE) must be received by central histopathology laboratory for correlative studies
- •-Patients with activated WNT/ß-catenin signaling identified by glutamine synthetase staining (high positive staining in tumor tissue) by an approved lab. Positive staining must be confirmed prior to first dose of DKN-01.
- •-Child-Pugh score <7 (Child-Pugh Class A).
- •-Barcelona Clinic Liver Cancer (BCLC) Stage C disease or BCLC Stage B disease not amenable to resection, locoregional therapy or refractory to locoregional therapy.
- •-At least one tumor lesion measurable on radiographic imaging as defined by mRECIST for HCC that has not been previously treated by locoregional therapies.
- •-Locoregional therapies or radiation therapy must be completed at least 4 weeks prior to baseline scan. All toxic effects > grade 1 (NCI CTCAE v4.03) related to any prior HCC treatment must be resolved. Palliative radiotherapy for symptomic control is acceptable and no additional radiotherapy for the same lesion is planned.
- •-ECOG performance status (PS) of 0 or 1.
- •-Estimated life expectancy of at least 3 months, in the judgment of the Investigator.
- •-Disease-free of active second/secondary or prior malignancies for =2 years with the exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix or breast.
- •-Patients are eligible to enroll if they have non-viral-HCC, or if they have HBV-HCC, or HCV-HCC defined as follows:
- •oHBV-HCC: Resolved HBV infection (as evidenced by detectable HBV surface antibody, detectable HBV core antibody, undetectable HBV DNA, and undetectable HBV surface antigen) or chronic HBV infection (as evidenced by detectable HBV surface antigen or HBV DNA). Patients with chronic HBV infection must have HBV DNA < 2000 IU/mL and must be on antiviral therapy.
- •oHCV-HCC: Active or resolved HCV infection as evidenced by detectable HCV RNA or antibody
- •-Acceptable liver function:
- •oTotal bilirubin =2.0 × upper limit of normal (ULN).
- •oAspartate aminotransferase (AST) and alanine aminotransferase (ALT) =5 × ULN.
- •-Acceptable renal function:
- •oCalculated creatinine clearance =50 mL/min using the Cockcroft and Gault Method (Cockroft and Gault 1976).
- •-Acceptable hematologic status:
- •oNeutrophil Granulocyte =1500 cells/µl.
- •oHemoglobin = 8,5 g/dL (= 5,28 mmol/l)(transfusion permitted within 30 days of study entry).
- •oPlatelet count =75,000 cells/µl.
- •-Acceptable coagulation status:
- •oINR = 1.7 and no active bleeding, (i.e., no clinically significant bleeding within 14 days prior to first dose of study therapy
- •-Female subjects who are post-menopausal (defined as spontaneous amenorrhea for at least a year) or permanently sterilized (e.g. bilateral oophorectomy, hysterectomy, bilateral salpingectomy) can participate in the trial
- •-Women of child bearing potential must have a negative serum or urine pregnancy test within 7 days prior to first dose of DKN-01. The minimum sensitivity of the pregnancy test must be 25 IU/L or equivalent units
排除标准
- •Patients presenting at least one of the following criteria will not be enrolled in the trial:
- •- -Patients with the following histology of hepatocellular cancer are not eligible for enrollment: fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma.
- •-New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, or unstable arrhythmia.
- •-Specific cardiac preconditions : Fridericia-corrected QT interval (QTcF) >470 msec (female) or >450 msec (male), or history of congenital long QT syndrome. Any ECG abnormality that in the opinion of the Investigator would preclude safe participation in the study; patients with pacemakers where QTc is not a reliable measure will require an evaluation by a cardiologist to exclude co-existing cardiac conditions which would prohibit safe participation in the study.
- •-Active, uncontrolled bacterial, viral, or fungal infections, within 7 days of study entry requiring systemic therapy.
- •-human immunodeficiency virus (HIV) positive,
- •-History of major organ transplant (i.e., heart, lungs, liver, or kidney).
- •-History of autologous/allogenic bone marrow transplant.
- •-Serious non-malignant disease that could compromise protocol objectives in the opinion of the Investigator and/or Sponsor.
- •-Pregnancy or nursing.
- •-Major surgical procedures, open biopsy or significant traumatic injury within 4 weeks prior to treatment start (minor procedures within 1 week)
- •-History of osteonecrosis of the hip or evidence of structural bone abnormalities in the proximal femur on magnetic resonance imaging (MRI) scan that are symptomatic and clinically significant. Degenerative changes of the hip joint are not exclusionary. Screening of asymptomatic patients is not required.
- •-Symptomatic central nervous system (CNS) malignancy or metastasis. Patients with treated CNS metastases are eligible provided their disease is radiographically stable, asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Screening of asymptomatic patients without a history of CNS metastases is not required.
- •-Known osteoblastic bone metastasis. Screening of asymptomatic patients without a history of metastatic bone lesions is not required.
- •-Medical or psychological conditions that would jeopardise an adequate and orderly completion of the trial.
- •-Thrombotic or embolic events (except HCC tumor thrombus -Evidence of portal hypertension with bleeding esophageal or gastric varices within the past 6 months
- •-Patients with portal thrombosis = pVT4
- •Medication Related
- •- prior systemic therapy for HCC
- •- Currently receiving any other investigational agent or received an investigational agent
- •within last 30 days prior to first dose or within 5 times the half-life of this agent before
- •the first dose of study treatment.
- •- Previously treated with an anti-DKK1 therapy.
- •- Treatment with strong inducers of CYP3A4 within 7 days prior to first dose (including
- •Cyclosporin, Erythromycin, Ketoconazole, Itraconazole, Quinidine, Phenobarbital salt
- •with Quinidine, Ritonavir, Valspodar, Verapamil, St John's wort, rifampicin).
- •- Significant allergy to a pharmaceutical therapy that, in the opinion of the Investigator,
- •poses an increased risk to the patient.
- •- History of hypersensitivity to the investigational medicinal product or to any drug with
- •similar chemical structure or to any excipient present in the pharma
研究者
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