Vancomycin in Patients With Unresectable Fibrolamellar Hepatocellular Carcinoma (FLC) Oral
|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: NCT04025567|
Recruitment Status : Not yet recruiting
First Posted : July 19, 2019
Last Update Posted : August 22, 2019
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.
To test if vancomycin is safe and tolerable for and can treat people with unresectable FLC.
People ages 18 and older with FLC that isn t responsive to treatment
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.
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Hepatocellular Carcinoma Hepatocellular Carcinoma||Drug: vancomycin||Phase 2|
- 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.
-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
- 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.
- 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of Oral Vancomycin in Patients With Unresectable Fibrolamellar Hepatocellular Carcinoma (FLC)|
|Estimated Study Start Date :||August 27, 2019|
|Estimated Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||December 31, 2021|
Experimental: 1/Arm 1
1,500 mg total daily dose, on days 1-21 of every 28 days cycle.
- 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
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): NCT04025567
|Contact: Donna M Hrones, C.R.N.P.||(240) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Not yet recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Tim F Greten, M.D.||National Cancer Institute (NCI)|