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

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ClinicalTrials.gov Identifier: NCT03781934
Recruitment Status : Recruiting
First Posted : December 20, 2018
Last Update Posted : March 7, 2019
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

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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 Phase 1b. SRC discretion to expand to include Child-Pugh B status for Phase 1a and Phase 1b. Must have a Child Pugh A or B status for Phase 2a. SRC discretion to restrict to Child Pugh A status for Phase 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 platelets ≥ 75,000/mL at Screening.
  10. Must have International Normalized Ratio (INR) ≤ 1.7 at Screening.
  11. Female who is postmenopausal, OR Female who is of childbearing potential 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.

  12. 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.

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

  • Histologically or cytologically confirmed 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 comprising, but not limited to, renal, colon, pancreatic, breast, lung, and gastric tumors, with limited extrahepatic tumor burden.

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. Positive hepatitis B surface antigen screen, and/or a positive HCV antibody screen.
  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 Screening.
  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
University Hospitals Gasthuisberg Recruiting
Leuven, Belgium, 3000
Contact: Eric Van Cutsem, Professor    +32 (0) 16344225    eric.vancutsem@uzleuven.be   
Contact: Hilde Marsé, Nurse    +32 (0) 16347583    Hilde.marse@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: Jacqueline Gourlay, Nurse    +44 (0) 141 301 7236    jacqueline.gourlay@glasgow.ac.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   
Sponsors and Collaborators
Medivir
Investigators
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Principal Investigator: Ruth Plummer, Professor Northern Institute for Cancer Research Newcastke

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Responsible Party: Medivir
ClinicalTrials.gov Identifier: NCT03781934     History of Changes
Other Study ID Numbers: MIV-818-101/201
First Posted: December 20, 2018    Key Record Dates
Last Update Posted: March 7, 2019
Last Verified: March 2019
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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Cholangiocarcinoma
Carcinoma, Hepatocellular
Liver Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases