Vancomycin in Patients With Unresectable Fibrolamellar Hepatocellular Carcinoma (FLC) Oral

NCT04025567 | Withdrawn Phase 2

• 2 other identifiers: 19012519-C-0125
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Metastatic Hepatocellular Carcinoma; Hepatocellular Carcinoma

Keywords

Gut Bacteria; Anti-Tumor Effects; NKT cells

Outcome Measures

Primary Outcomes (1)

• 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

  4 weeks

Study Arms (1)

1/Arm 1

EXPERIMENTAL

Oral vancomycin

Drug: vancomycin

Interventions

vancomycin DRUG

1,500 mg total daily dose, on days 1-21 of every 28 days cycle.

1/Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Vancomycin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Tim F Greten, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2019
• First Posted: July 19, 2019
• Study Start: March 12, 2020
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: March 16, 2020

Record last verified: 2020-03

Locations

US (1)