Phase 1/2a study to evaluate the safety, activity, and pharmacokinetics of escalating doses of GNS561 in patients with primary or secondary liver cancer
- Conditions
- Hepatocellular carcinomaIntrahepatic cholangiocarcinomaPancreatic adenocarcinoma with liver metastasisColorectal cancer with liver metastasisMedDRA version: 20.0Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectableSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10077738Term: Hepatocellular carcinoma metastaticSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10073077Term: Intrahepatic cholangiocarcinomaSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10033599Term: Pancreatic adenocarcinoma metastaticSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-003585-27-BE
- Lead Sponsor
- GENOSCIENCE PHARMA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 122
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
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method