Phase 1/2a study to evaluate the safety, activity, and pharmacokinetics of escalating doses of GNS561 in patients with primary or secondary liver cancer

GENOSCIENCE PHARMA0 个研究点目标入组 122 人开始时间: 2017年10月6日最近更新: 2019年11月25日

适应症

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: GENOSCIENCE PHARMA
入组人数: 122

研究概览入排标准研究者记录与标识符相似试验

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

•1. Males or females = 18 years of age.
•2. Histologically confirmed and documented locally advanced or metastatic hepatocarcinoma (HCC) that is deemed not appropriate for curative therapy or histologically confirmed and documented locally advanced or metastatic intrahepatic carcinoma (iCCA) or or histologically confirmed and documented pancreatic ductal adenocarcinoma (PDAC) with liver metastasis or histologically confirmed and documented colorectal cancer (CRC) with liver metastasis.
•3. Liver tumor burden < 50% of the liver (per Investigator judgment).
•4. Antiviral therapy required in Hepatitis B virus patients (Hepatitis B antigen positive)
•5. Child-Pugh score A (= 6, Appendix C), with no evidence of prior cirrhotic decompensation within last 12 months prior to enrollment.
•6. a. Previously exposed, intolerant or refractory to at least another registered therapy and for which no curative therapy is available for HCC.
•b. Previously exposed, intolerant or refractory to at least one first line chemotherapy for ICC.
•c. Previously exposed, intolerant or refractory to at least one first line chemotherapy and for which no curative therapy is available for PDAC patients.
•d. Previously exposed, intolerant or refractory to at least one first line chemotherapy with fluoropyrimidine and/or oxaliplatin and/or irinotecan and for which no curative therapy is available for CRC patients.
•7. Neither sorafenib nor other anticancer therapy such as chemotherapy in the 4 weeks or 5 half-lives, whichever is greater, prior to the first dose of GNS561. This treatment-free period must be extended to 6 weeks in the case of nitrosoureas and 8 weeks for previous treatment with monoclonal antibodies. The following treatment is allowed: palliative radiation to bone metastases within 2 weeks prior to first dose.
•8. Willing to have liver biopsy at the beginning of Cycle 2 (Day 1 ) in escalation phase.
•9. Presence of a measurable tumor per RECIST v1.1 criteria (Appendix E)
•10. Eastern Cooperative Oncology Group (ECOG) performance status = 1 (Appendix D)
•11. Life expectancy = 12 weeks
•12. Adequate hematologic function prior to the first dose of GNS561, defined as:
•a. Absolute neutrophils count = 1500 cells/µL
•b. Hemoglobin = 10 g/dL with no transfusion within 4 weeks prior to first planned dose of GNS561
•c. Platelet count > 50,000/µL with no transfusion within 2 weeks prior to first planned dose of GNS561
•13. Adequate renal function prior to first dose, defined as
•a. Serum creatinine < 1.5 upper limit of normal (ULN)
•b. Creatinine clearance = 50 mL/min/m2 (by Cockroft-Gault equation of 24-hour urine) if creatinine = 1.5 X ULN
•14. Adequate hepatic function prior to first dose, defined as aspartate aminotransferase (AST)/alanine aminotransferase (ALT) = 5 x ULN
•15. Women patients of childbearing potential must have a negative serum/urine pregnancy test at screening and baseline, and be willing to use a medically acceptable form, as judged by the Investigator and Sponsor, of contraception (e.g., hormonal birth control, intrauterine device [IUD], or bilateral tubal occlusion or abstinence or whose partner had a vasectomy at least 2 years before screening). The patient should be advised to continue the contraception for at least 6 months following the completion of dosing. Women with cessation for > 24 months of previously occurring menses, or women of any age who have had a hysterectomy, or have had both ovaries removed will be considered to be of non-childbearing pote

排除标准

•1. Pregnant or breast-feeding mothers
•2. Prior history of acrodermatitis enteropathica or known ZIP4 genetic mutations
•3. Any known history of encephalopathy
•4. Known esophageal varices with recent history of bleeding (within previous 2 months)
•5. Clinically significant ascites or paracentesis
•6. Concurrent hematologic malignancies or other malignancy, with the exception of:
•a) Curatively resected non-melanoma skin cancer;
•b) Curatively treated cervical carcinoma in situ.
•7. Known untreated or symptomatic brain metastases
•8. Prior antitumor treatment, including chemotherapy, biologic, experimental, hormonal or radiotherapy within 4 weeks of first dose of GNS561with the following exceptions:
•a. Maintenance hormonal therapy for metastatic prostate and breast cancer
•b. Hormone-replacement therapy or oral contraceptives
•c. Palliative radiation to bone metastases within 2 weeks prior to first dose
•9. Previous treatment with ZIP4 targeted therapy
•10. Known allergic reaction to quinoline derivatives (e.g., quinine, chloroquine, Mefloquine)
•11. Presence of residual toxicities of = Grade 2 after prior antitumor therapy =4 weeks prior to first dose. Grade 1 toxicities related to previous treatments are acceptable at the time of the first planned dose of GNS561, as well as any alopecia.
•12. Chronic treatment with immunosuppressive agents(like steroids) = 6 weeks prior to first planned dose of GNS561.
•13. Major surgical procedures, open biopsy or significant traumatic injury = 4 weeks prior to first dose of GNS561 or anticipation of major surgical procedure during the course of the trial, minor surgical procedures = 1 week of first planned dose
•14. Any clinically significant cardiovascular condition as judged by the Investigator
•15. Severe or uncontrolled renal condition
•16. Untreated chronic hepatitis B
•17. Known history of immunodeficiency diseases (e.g., active HIV)
•18. Use of any prohibited concomitant medications within 14 days of the Baseline/Day 1 visit
•19. Known current alcohol (> 20g/ Day in women and >30g/ Day in men) or substance abuse
•20. Malabsorption issues (e.g., gastric bypass or gastrectomy patients)
•21. Patient with a mental or legal disability
•22. Participation in any investigational clinical investigation =4 weeks prior to first planned dose of GNS561 or longer if required by local regulations, and for any other limitation of participation based on local regulations
•23. Known clinically significant or life threatening organ or systemic disease such that in the opinion of the Investigator, the significance of the disease will compromise the patient’s participation in the trial
•24. Is a participant or plans to participate in another investigational clinical study, while taking part in this study.
•25. Known intolerance or hypersensitivity to the active ingredient or to one of the components of the study drug

研究者

发起方

GENOSCIENCE PHARMA

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