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A Study to Evaluate MIV-818 in Patients With Liver Cancer Manifestations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03781934
Recruitment Status : Recruiting
First Posted : December 20, 2018
Last Update Posted : March 19, 2020
Sponsor:
Information provided by (Responsible Party):
Medivir

Brief Summary:
This is a multicentre, open-label study to assess safety and tolerability of MIV-818 in patients with various solid tumours that have spread to the liver, or alternatively originating in the liver.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Intrahepatic Cholangiocarcinoma Liver Metastases Drug: MIV-818 Phase 1 Phase 2

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. All patients will receive an initial probe dose before entering the actual treatment cycles. Once pre-defined criteria for starting phase 1b has been met among the enrolled patients in phase 1a, the next phase of the study will be initiated. Phase 1b will enroll up to 30 patients in a 3+3 design with interpatient dose escalations. All dose escalation decisions will be made by an independent safety review committee that will meet regularly during the study conduct. As the MTD has been met, the SRC will provide a RP2D which will initiate phase 2a of the study. In phase 2a only HCC and iCCA patients will be recruited into two expansion cohorts.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 102 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Intrapatient dose escalations continuing into interpatient dose escalations to end with dose expansion cohorts.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2a Study in 3 Parts to Evaluate Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of MIV-818 in Patients With Liver Cancer Manifestations
Actual Study Start Date : September 5, 2018
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021


Arm Intervention/treatment
Experimental: HCC
Phase 2a expansion cohort HCC
Drug: MIV-818
Oral Capsules

Experimental: iCCA
Phase 2a expansion cohort iCCA
Drug: MIV-818
Oral Capsules




Primary Outcome Measures :
  1. Number of participants with treatment related AEs as assessed by CTCAE v5.0 [ Time Frame: Participants monitored throughout treatment period and during follow-up, up to 2 years ]
    1. Clinically significant changes in laboratory paramaters
    2. Clinically significant changes in ECGs
    3. Clinically significant changes in vital signs; heart rate
    4. c. Clinically significant changes in vital signs; weight in kg
    5. c. Clinically significant changes in vital signs; height in cm


Secondary Outcome Measures :
  1. Preliminary efficacy by means of RECIST evaluation [ Time Frame: Participants monitored throughout treatment period every 6 weeks until disease progression, up to 1 year ]
    1. ORR will be assessed by monitoring tumor response and progression using RECIST v1.1
    2. ORR will be assessed by monitoring tumor response and progression using mRECIST



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female ≥ 18 years of age on the day of signing informed consent.
  2. Able to understand and voluntarily sign a written informed consent and is willing, and able, to comply with the protocol requirements.
  3. 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.
  4. 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.
  5. Must have an ECOG performance status of 0 or 1 at Screening.
  6. Must have life expectancy of > 12 weeks in the investigator's opinion.
  7. Must have ALT and AST ≤ 5.0 × upper limit of normal (ULN) at Screening.
  8. Must have total bilirubin (TBil) ≤ 3.0 mg/dL at Screening.
  9. Must have adequate renal function with estimated creatinine clearance ≥ 60 mL/min (based on Cockcroft and Gault formula or similar) at Screening
  10. Must have platelets ≥ 75,000/mL at Screening.
  11. Must have International Normalized Ratio (INR) ≤ 1.7 at Screening.
  12. 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 soecific Inclusion Criteria

  14. Must have progressed on or are intolerant of standard therapy with:

    1. 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
    2. Histologically or cytologically confirmed iCCA, or
    3. 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).

Exclusion Criteria:

  1. Tumor volume exceeding 50% of liver.
  2. History of previous malignancy within the last 5 years except basal cell carcinoma or carcinoma in situ in solid organ.
  3. Known CNS or brain metastases, unless previously treated and stable for 3 months.
  4. Ongoing significant disease other than target disease as judged by the investigator to compromise the patients' ability to complete this study.
  5. History of solid organ transplant or bone marrow transplant.
  6. Receiving immunosuppressive therapy including oral corticosteroids.
  7. Active hepatitis B (eg, hepatitis B surface antigen [HBsAg] reactive) and patients with active hepatitis C (eg, hepatitis C RNA is [qualitative] detected).
  8. Positive human immunodeficiency virus (HIV) infection.
  9. Poorly controlled ascites and/or requirement for therapeutic paracentesis more frequently than once every 3 months.
  10. Symptomatic encephalopathy within 3 months prior to Screening and/or requirement for medication for encephalopathy.
  11. Esophageal variceal bleeding within 2 weeks prior to Screening.
  12. Receiving prior anticancer therapy within 4 weeks prior to first dose of MIV-818.
  13. Receiving any other investigational agent within 4 weeks prior to Screening
  14. Enrolled in another clinical study with an investigational drug.
  15. Presence of residual toxicities of CTCAE Grade > 1 after prior anticancer therapy within 2 weeks of first treatment with MIV-818, except for alopecia.
  16. History of allergic reactions attributed to compounds of similar chemical or biological composition to MIV-818.
  17. HCC of diffuse infiltrative type.
  18. Receiving drugs that are extensively metabolized by CYP3A4.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03781934


Contacts
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Contact: Linda Basse +46854683100 linda.basse@medivir.com
Contact: Sara Hedman +46854683100 sara.hedman@medivir.com

Locations
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Belgium
Antwerp University Hospital Recruiting
Antwerp, Belgium, 2650
Contact: Hans Prenen, Professor    +3238213646    hans.prenen@uza.be   
University Hospitals Gasthuisberg Recruiting
Leuven, Belgium, 3000
Contact: Eric Van Cutsem, Professor    +32 (0) 16344225    eric.vancutsem@uzleuven.be   
Contact: Nathalie Devolder, Nurse    +32 (0) 16341940    nathalie.devolder@uzleuven.be   
United Kingdom
Beatson West of Scotland Cancer Care Recruiting
Glasgow, United Kingdom, G12 0YN
Contact: Jeff Evans, Professor    +44 (0) 141 301 7073    jeff.evans@ggc.scot.nhs.uk   
Contact: Laura Cunningham, Nurse    +44 (0) 141 301 7229    laura.cunningham4@ggc.scot.nhs.uk   
Guy's Hospital, Oncology and Clinical Trials Recruiting
London, United Kingdom, SE1 9RT
Contact: Debashis Sarker, MD, PhD    +4420871887188 ext 5383    debashis.sarker@kcl.ac.uk   
Contact: Michael Flanagan, Nurse    +442071888103    michael.flanagan@gstt.nhs.uk   
Northern Institute for Cancer Research Recruiting
Newcastle Upon Tyne, United Kingdom, NE2 4HH
Contact: Ruth Plummer, Professor    +44 (0)191 213 6161    ruth.plummer@newcastle.ac.uk   
Contact: Katherine Stevensson, Nurse    +44 191 213 8437    katherine.stevensson@nuth.nhs.uk   
Chruchill Hospital, Cancer and Haematology Centre Recruiting
Oxford, United Kingdom, OX3 7LE
Contact: Mark Middleton, Professor       mark.middleton@oncology.ox.ac.uk   
Contact: David Mukkath, Nurse    +441865572027    trialadministrator04@oncology.ox.ac.uk   
Sponsors and Collaborators
Medivir
Investigators
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Principal Investigator: Ruth Plummer, Professor Northern Institute for Cancer Research, Newcastle
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Responsible Party: Medivir
ClinicalTrials.gov Identifier: NCT03781934    
Other Study ID Numbers: MIV-818-101/201
First Posted: December 20, 2018    Key Record Dates
Last Update Posted: March 19, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Liver Neoplasms
Cholangiocarcinoma
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Carcinoma, Hepatocellular
Adenocarcinoma
Carcinoma
Digestive System Diseases
Liver Diseases