Metastatic Hepatocellular CarcinomaPhase 2NCT04025567
Vancomycin in Patients With Unresectable Fibrolamellar Hepatocellular Carcinoma (FLC) Oral
A Phase 2 study testing vancomycin in people with Metastatic Hepatocellular Carcinoma and Hepatocellular Carcinoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: Fibrolamellar Hepatocellular Carcinoma (FLC) is a rare liver cancer. It most often occurs in young people who have no history of liver disease. Unresectable FLC most often does not improve with surgery. Researchers think gut bacteria may affect liver cancer control. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Hepatocellular Carcinoma, Hepatocellular Carcinoma
- What is being tested?
- vancomycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Mar 2020to 31 Dec 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histopathological confirmation of FLC by the NCI Laboratory of Pathology.
- Patients must have disease that is not amenable to potentially curative resection, transplantation or ablation.
- Patients must be greater than or equal to 18 years of age. Children are excluded from this study because this study has two mandatory biopsies performed for research purposes only and we do not want to put children into additional risk of biopsies.
- Patients must have evaluable or measurable hepatic disease per RECIST 1.1
- Patients must have hepatic lesion accessible for biopsy and be willing to undergo pre- and post-treatment mandatory biopsies.
- ECOG performance status of less than or equal to 2
Show all 17Show fewer
- Adequate renal function defined by:
- Creatinine <1.5 x institution upper limit of normal (ULN)
- Creatinine clearance (CrCl) greater than or equal to 50 mL/min/1.73 m2 by 24 hours urine collection or eGFR as estimated using the chronic kidney disease (CKD)-EPI equation for participant with creatinine levels > 1.5 X institutional ULN.
- Adequate hepatic function defined by:
- Total bilirubin level with upper limit of normal less than or equal to 1 (SqrRoot) ULN,
- AST level <5(SqrRoot) ULN, and
- ALT level <5 (SqrRoot) ULN.
- Adequate hematological function defined by:
- --Absolute neutrophil count (ANC) greater than or equal to 1.5 (SqrRoot) 109/L.
- Subjects must be co-enrolled onto protocol 11C0112.
- Ability of subject or Legally Authorized Representative to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients who have had standard-of-care anti-cancer therapy (e.g., chemotherapy,immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies or other investigation agents) within 2 weeks of enrollment; or, therapy with investigational agents, large field radiotherapy, or major surgery within 4 weeks prior to enrollment.
- Patients who are currently receiving any other investigational agents for any indication.
- Patients who are actively receiving broad-spectrum antibiotics or have received such within 4 weeks prior to enrollment.
- Patients with history of recurrent C. diff colitis
- Patients who are on anti-coagulation or anti-platelet medication that cannot be interrupted prior to study-specified biopsies, including:
- Aspirin that cannot be discontinued for 7 days prior to biopsy
Show all 16Show fewer
- Clopidogrel and ticagrelor that cannot be discontinued for 5 days prior to biopsy
- Ticlopidine that cannot be discontinued for 10 days prior to biopsy
- Prasugrel that cannot be discontinued for 7 days prior to biopsy
- Dipyridamole that cannot be discontinued for at least 2 days prior to biopsy
- Cilostazol that cannot be discontinued for at least 3 days prior to biopsy
- Coumadin that cannot be discontinued for 7 days prior to biopsy
- Low molecular weight heparin (LMWH) that cannot be discontinued >24 hours prior to biopsy and unfractionated heparin (UFH) that cannot be discontinued >4 hours prior to biopsy. NOTE: LMWH or UFH may be used to transition patients on and off the above anti-coagulants, if deemed appropriate by the treating physician.
- Oral direct thrombin inhibitor (dabigatran) or direct Factor Xa inhibitor (rivaroxaban, apixaban, and edoxaban) that cannot be discontinued for 4 days prior to biopsy
- Any other uncontrolled intercurrent illness or medical condition that per PI discretion would limit compliance with study requirements.
- Pregnant women are excluded from this study because this study has two mandatory biopsies performed for research purposes only and biopsies can have abortifacient effect.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Phase II Study of Oral Vancomycin in Patients With Unresectable Fibrolamellar Hepatocellular Carcinoma (FLC)
Background:
Fibrolamellar Hepatocellular Carcinoma (FLC) is a rare liver cancer. It most often occurs in young people who have no history of liver disease. Unresectable FLC most often does not improve with surgery. Researchers think gut bacteria may affect liver cancer control. They want to see if a drug that controls a type of bacteria can help.
Read more
Objective:
To test if vancomycin is safe and tolerable for and can treat people with unresectable FLC.
Eligibility:
People ages 18 and older with FLC that isn t responsive to treatment
Design:
Participants will be screened with a medical history, physical exam, blood and urine tests, and CT or MRI scans. They will provide a tumor sample: If they do not have one, they will have a biopsy.
Participants will take vancomycin 3 times a day. They will take the drug by mouth. They will take the drug in 28-day cycles. They will take the drug daily for the first 3 weeks. They will not take the drug the last week.
Participants will keep a medication diary.
Participants will have blood and urine tests each cycle. They may provide stool samples.
Participants will have a biopsy before they start treatment. Then they will have one on day 1 of cycle 2.
Participants will have scans on day 1 of cycle 2. Then they will have scans about every 8 weeks.
Participants will continue treatment until their cancer gets worse or they can no longer tolerate the side effects.
Participants will have a follow-up visit about a month after they finish treatment. Then they will be followed every 6 months by phone or email.
Read the detailed description
Background:
- Fibrolamellar hepatocellular carcinoma (FLC) is a rare liver cancer (0.5-9% of primary liver cancers), which affects younger age groups and is not associated with underlying liver disease or elevated serum alpha fetoprotein (AFP) levels.
- Surgery, either liver resection (LR) or liver transplantation (LT), is the only potentially curative treatment for FLC patients with resectable disease. Disease recurrence after complete resection is high (33-100%). In patients with unresectable disease, median survival is less than 12 months; with no patient expected to survive beyond 5 years.
- The role of systemic chemotherapy and radiotherapy is poorly defined, and has been reported to have only a modest or no therapeutic effect. To date no targeted therapy has been shown to be of any value in FLC.
- In mouse models, oral vancomycin alters gut commensal bacteria thereby inducing a liver-selective anti-tumor effect by increasing hepatic CXCR6+ NKT cells via increased CXCL16 expression of liver sinusoidal endothelial cells.
Objective:
-To evaluate the effect of oral vancomycin therapy on the relative CXCR6 gene expression levels in the liver in paired pre- and on-treatment biopsy samples from hepatic lesions in patients with unresectable FLC
Eligibility:
- Histologically confirmed FLC, not amenable to potentially curative resection, transplantation or ablation.
- Liver lesion measurable by RECIST criteria, accessible for biopsy.
- Age greater than or equal to 18 years
- ECOG performance status less than or equal to 2
- Acceptable renal and normal liver function.
- Willingness to undergo pre- and on-treatment biopsies of liver tumor.
Design:
- This is a phase II study of oral vancomycin in patients with unresectable FLC.
- Up to 14 patients will be treated with oral vancomycin 500 mg tid daily (1,500 mg total daily dose) from days 1 to 21, in a 28-day cycles. After completion of the first cycle, initiation of concurrent treatment will be allowed. Patients will receive oral vancomycin until off treatment criteria are met.
- Patients will be evaluated for toxicity every 4 weeks by CTCAE v5.0, and for response at the end of the first cycle and thereafter every 8 (+/-3) weeks by RECIST 1.1.
- Being tested
- vancomycin
- Keywords
- Gut Bacteria, Anti-Tumor Effects, NKT cells
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vancomycinDrug
1,500 mg total daily dose, on days 1-21 of every 28 days cycle.
| Study group | Role | What they receive |
|---|---|---|
| 1/Arm 1 | Experimental | Oral vancomycin Receives: Drug: vancomycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the effect of oral vancomycin therapy in the relative CXCR6 gene expression levels in the liver
Change from baseline to 4 weeks after starting treatment in the relative CXCR6 gene expression level in the liver as determined by mRNA with Nanostring
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2019
- Study start12 Mar 2020 (estimated)
- Primary completion31 Dec 2021 (estimated)
- Study completion31 Dec 2021 (estimated)
Why it stopped: slow/insufficient accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Tim F Greten, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04025567
- Sponsor's protocol ID
- 190125
- Other IDs
- 19-C-0125
- Status last verified
- Mar 2020
- First submitted
- 18 Jul 2019
- Last updated
- 16 Mar 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Oral Vancomycin in Patients With Unresectable Fibrolamellar Hepatocellular Carcinoma (FLC)
- ClinicalTrials.gov ID
- NCT04025567
- Acronym / sponsor ID
- 190125
- Keywords
- Gut Bacteria, Anti-Tumor Effects, NKT cells
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: slow/insufficient accrual.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 12 Mar 2020 (estimated)
- Primary completion
- 31 Dec 2021 (estimated)
- Study completion
- 31 Dec 2021 (estimated)
- First posted
- 19 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Fibrolamellar Hepatocellular Carcinoma (FLC) is a rare liver cancer. It most often occurs in young people who have no history of liver disease. Unresectable FLC most often does not improve with surgery. Researchers think gut bacteria may affect liver cancer control. They want to see if a drug that controls a type of bacteria can help.
Objective:
To test if vancomycin is safe and tolerable for and can treat people with unresectable FLC.
Eligibility:
People ages 18 and older with FLC that isn t responsive to treatment
Design:
Participants will be screened with a medical history, physical exam, blood and urine tests, and CT or MRI scans. They will provide a tumor sample: If they do not have one, they will have a biopsy.
Participants will take vancomycin 3 times a day. They will take the drug by mouth. They will take the drug in 28-day cycles. They will take the drug daily for the first 3 weeks. They will not take the drug the last week.
Participants will keep a medication diary.
Participants will have blood and urine tests each cycle. They may provide stool samples.
Participants will have a biopsy before they start treatment. Then they will have one on day 1 of cycle 2.
Participants will have scans on day 1 of cycle 2. Then they will have scans about every 8 weeks.
Participants will continue treatment until their cancer gets worse or they can no longer tolerate the side effects.
Participants will have a follow-up visit about a month after they finish treatment. Then they will be followed every 6 months by phone or email.
Detailed description
Background:
- Fibrolamellar hepatocellular carcinoma (FLC) is a rare liver cancer (0.5-9% of primary liver cancers), which affects younger age groups and is not associated with underlying liver disease or elevated serum alpha fetoprotein (AFP) levels.
- Surgery, either liver resection (LR) or liver transplantation (LT), is the only potentially curative treatment for FLC patients with resectable disease. Disease recurrence after complete resection is high (33-100%). In patients with unresectable disease, median survival is less than 12 months; with no patient expected to survive beyond 5 years.
- The role of systemic chemotherapy and radiotherapy is poorly defined, and has been reported to have only a modest or no therapeutic effect. To date no targeted therapy has been shown to be of any value in FLC.
- In mouse models, oral vancomycin alters gut commensal bacteria thereby inducing a liver-selective anti-tumor effect by increasing hepatic CXCR6+ NKT cells via increased CXCL16 expression of liver sinusoidal endothelial cells.
Objective:
-To evaluate the effect of oral vancomycin therapy on the relative CXCR6 gene expression levels in the liver in paired pre- and on-treatment biopsy samples from hepatic lesions in patients with unresectable FLC
Eligibility:
- Histologically confirmed FLC, not amenable to potentially curative resection, transplantation or ablation.
- Liver lesion measurable by RECIST criteria, accessible for biopsy.
- Age greater than or equal to 18 years
- ECOG performance status less than or equal to 2
- Acceptable renal and normal liver function.
- Willingness to undergo pre- and on-treatment biopsies of liver tumor.
Design:
- This is a phase II study of oral vancomycin in patients with unresectable FLC.
- Up to 14 patients will be treated with oral vancomycin 500 mg tid daily (1,500 mg total daily dose) from days 1 to 21, in a 28-day cycles. After completion of the first cycle, initiation of concurrent treatment will be allowed. Patients will receive oral vancomycin until off treatment criteria are met.
- Patients will be evaluated for toxicity every 4 weeks by CTCAE v5.0, and for response at the end of the first cycle and thereafter every 8 (+/-3) weeks by RECIST 1.1.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1/Arm 1 | Experimental | Drug: vancomycinOral vancomycin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patients must have histopathological confirmation of FLC by the NCI Laboratory of Pathology.
- Patients must have disease that is not amenable to potentially curative resection, transplantation or ablation.
- Patients must be greater than or equal to 18 years of age. Children are excluded from this study because this study has two mandatory biopsies performed for research purposes only and we do not want to put children into additional risk of biopsies.
- Patients must have evaluable or measurable hepatic disease per RECIST 1.1
- Patients must have hepatic lesion accessible for biopsy and be willing to undergo pre- and post-treatment mandatory biopsies.
Key exclusion criteria (16 listed)
- Patients who have had standard-of-care anti-cancer therapy (e.g., chemotherapy,immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies or other investigation agents) within 2 weeks of enrollment; or, therapy with investigational agents, large field radiotherapy, or major surgery within 4 weeks prior to enrollment.
- Patients who are currently receiving any other investigational agents for any indication.
- Patients who are actively receiving broad-spectrum antibiotics or have received such within 4 weeks prior to enrollment.
- Patients with history of recurrent C. diff colitis
- Patients who are on anti-coagulation or anti-platelet medication that cannot be interrupted prior to study-specified biopsies, including:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| vancomycin1,500 mg total daily dose, on days 1-21 of every 28 days cycle. | Drug | 1/Arm 1 |
Primary outcome
To evaluate the effect of oral vancomycin therapy in the relative CXCR6 gene expression levels in the liver
Time frame: 4 weeks
Change from baseline to 4 weeks after starting treatment in the relative CXCR6 gene expression level in the liver as determined by mRNA with Nanostring
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2020.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Related trials for Metastatic Hepatocellular Carcinoma
RecruitingObservational study
Real-world Evaluation of the HistoSonics Edison System for Treatment of Liver Tumors Across Multidisciplinary Users (BOOMBOX: Master Study)
Liver Neoplasms, Primary Liver Cancer
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingPhase 1/2
A Phase 1 and 2 Study of VMD-102 in Hepatocellular Carcinoma and Other Solid Tumors
Hepatocellular Carcinoma (HCC), Metastatic Uveal Melanoma
RecruitingPhase 2
DB-1311 in Combination With BNT327 or DB-1305 in Advanced/Metastatic Solid Tumors
Solid Tumors
Not yet recruitingObservational study
Immune-Related Adverse Events and Clinical Outcomes of First-Line Immunotherapy in Egyptian Patients With Unresectable Hepatocellular Carcinoma
Hepatocellular Carcinoma, Hepatocellular Carcinoma (HCC)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tim F Greten, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing vancomycin in people with Metastatic Hepatocellular Carcinoma and Hepatocellular Carcinoma, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 16 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the effect of oral vancomycin therapy in the relative CXCR6 gene expression levels in the liver (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2020.