Status:
COMPLETED
A Study to Evaluate MIV-818 in Patients With Liver Cancer Manifestations
Lead Sponsor:
Medivir
Conditions:
Hepatocellular Carcinoma
Intrahepatic Cholangiocarcinoma
Eligibility:
All Genders
18+ years
Phase:
PHASE1
PHASE2
Brief Summary
This is an open-label, multicentre dose escalation/expansion study to assess safety and tolerability of MIV 818 as either monotherapy or in combination with 1) lenvatinib, a tyrosine kinase inhibitor ...
Detailed Description
This study will be conducted in three phases. The initial phase, 1a, will enroll up to 12 subjects and include a total of one dose escalation per patient. Once pre-defined criteria for starting phase ...
Eligibility Criteria
Inclusion
- Inclusion criteria:
- Male or female ≥ 18 years of age on the day of signing informed consent.
- Able to understand and voluntarily sign a written informed consent and is willing, and able, to comply with the protocol requirements.
- Must have measurable disease based on RECIST v1.1 as determined by the site study team. Must have at least 1 target lesion in the liver. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- Must have a Child-Pugh A status for Phase 1a and a Child-Pugh A or B status for Phase 1b and 2a. SRC discretion to restrict to Child-Pugh A status for Phase 1b and 2a.
- Must have an ECOG performance status of 0 or 1 at Screening.
- Must have life expectancy of \> 12 weeks in the investigator's opinion.
- Must have ALT and AST ≤ 5.0 × upper limit of normal (ULN) at Screening.
- Must have total bilirubin (TBil) ≤ 3.0 mg/dL at Screening.
- Must have adequate renal function with estimated creatinine clearance
- ≥ 60 mL/min (based on Cockcroft and Gault formula or similar) at Screening
- Must have platelets ≥ 75,000/mL at Screening.
- Must have International Normalized Ratio (INR) ≤ 1.7 at Screening. Female who is postmenopausal, OR Female who is of childbearing potential (postmenarchal) who agrees to use a highly efficient method of contraception (ie, a method with less than 1% failure rate \[eg, sterilization, hormone implants, hormone injections, intrauterine devices, or vasectomized partner or combined birth control pills\]) from Screening until 90 days after the final dose of MIV-818.
- OR Male who agrees to use condoms from Screening until 90 days after the final dose of MIV-818.
- OR Male with a female partner of childbearing potential (WOCBP) who is using a highly efficient method of contraception as described above.
- 13\. WOCBP must have a negative serum pregnancy test at Screening and negative (serum or urine) pregnancy test within 72 h before the first study drug dose.
- Phase 1a and 1b specific
- 14\. Must have progressed on or are intolerant of standard therapy with:
- Histologically or cytologically confirmed HCC, including fibrolamellar HCC; patients with HCC that received their diagnosis according to the agreed international radiological guideline are also admissible upon agreement between the investigator and the medical monitor, or
- Histologically or cytologically confirmed iCCA, or
- Liver metastases from colon, rectal, or gastric solid tumors with limited extrahepatic tumor burden (any extrahepatic metastases should be limited to 1 other site and a maximum of 1 target lesion outside the liver).
- Phase 1b Monotherapy-specific Inclusion Criterion:
- 15\. Must have:
- Histologically or cytologically confirmed HCC, including fibrolamellar HCC; patients with HCC that received their diagnosis according to the agreed international radiological guideline are also admissible upon agreement between the investigator and the medical monitor, or
- Histologically or cytologically confirmed iCCA, or
- Liver metastases from solid tumors, with limited extrahepatic tumor burden (i.e. no brain or bone metastases), any extrahepatic metastases should be limited to 1 other site and a maximum of 1 target lesion outside the liver).
- Combination therapy-specific Inclusion Criterion:
- 16\. Must have histologically or cytologically confirmed HCC that is considered advanced or unresectable, i.e. not suitable for either surgery, radiofrequency ablation (RFA) or loco-regional therapies (patients with HCC that received their diagnosis according to the agreed international radiological guideline are also admissible upon agreement between the investigator and medical monitor). Patients with fibrolamellar HCC or a mixed HCC and iCCA will be excluded.
- 17\. Must have progressed on or are intolerant of 1or 2 lines of standard therapy for HCC (see also exclusion criterion no. 20) and are now candidates for lenvatinib or pembrolizumab treatment.
Exclusion
- Tumor volume exceeding 50% of liver.
- History of previous malignancy within the last 5 years except basal cell carcinoma or carcinoma in situ in solid organ.
- Known CNS or brain metastases, unless previously treated and stable for 3 months.
- Ongoing significant disease other than target disease as judged by the investigator to compromise the patients' ability to complete this study.
- History of solid organ transplant or bone marrow transplant.
- Receiving immunosuppressive therapy including oral corticosteroids.
- Active hepatitis B (eg, hepatitis B surface antigen \[HBsAg\] reactive) and patients with active hepatitis C (eg, hepatitis C RNA is \[qualitative\] detected).
- Positive human immunodeficiency virus (HIV) infection.
- Poorly controlled ascites and/or requirement for therapeutic paracentesis more frequently than once every 3 months.
- Symptomatic encephalopathy within 3 months prior to Screening and/or requirement for medication for encephalopathy.
- Esophageal variceal bleeding within 2 weeks prior to Screening.
- Receiving prior anticancer therapy within 4 weeks prior to first dose of MIV-818.
- Receiving any other investigational agent within 4 weeks prior to Screening
- Enrolled in another clinical study with an investigational drug.
- Presence of residual toxicities of CTCAE Grade \> 1 after prior anticancer therapy within 2 weeks of first treatment with MIV-818, except for alopecia.
- History of allergic reactions attributed to compounds of similar chemical or biological composition to MIV-818.
- HCC of diffuse infiltrative type.
- Receiving drugs that are extensively metabolized by cytochrome P450 (CYP) 3A4 that have a narrow therapeutic index. Drugs that are extensively metabolized by CYP3A4 that have a narrow therapeutic index must be discontinued 5 half-lives before first dose of MIV-818.
- Combination therapy-specific
Key Trial Info
Start Date :
September 5 2018
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
June 16 2025
Estimated Enrollment :
53 Patients enrolled
Trial Details
Trial ID
NCT03781934
Start Date
September 5 2018
End Date
June 16 2025
Last Update
July 1 2025
Active Locations (18)
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1
Antwerp University Hospital
Antwerp, Belgium, 2650
2
University Hospitals Gasthuisberg
Leuven, Belgium, 3000
3
CHA Bundang Medical Center
Gyeonggi-do, South Korea
4
Pusan National University Hospital
Pusan, South Korea