Nivolumab (Anti-PD1), Tadalafil and Oral Vancomycin in People With Refractory Primary Hepatocellular Carcinoma or Liver Dominant Metastatic Cancer From Colorectal or Pancreatic Cancers
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|ClinicalTrials.gov Identifier: NCT03785210|
Recruitment Status : Recruiting
First Posted : December 24, 2018
Last Update Posted : April 20, 2020
A most common liver cancer in adults is hepatocellular carcinoma. Other kinds of liver cancer happen when colorectal or pancreatic cancer spreads to the liver. Researchers want to study if a combination of drugs helps people with these cancers. The drugs are nivolumab, tadalafil, and vancomycin.
To investigate if nivolumab given with tadalafil and vancomycin causes liver cancer to shrink.
Adults ages 18 years and older with hepatocellular carcinoma or metastases to the liver from colorectal or pancreatic cancer for which standard treatment has not worked
Participants will be screened with:
Medical and cancer history
Review of symptoms and ability to perform normal activities
Heart test. Some participants may meet with a cardiologist and/or have another heart test.
Scan of the chest, abdomen, and pelvis
Blood and urine tests
Tumor sample review. This can be from a previous procedure.
Participants will receive the study drugs in 4-week cycles. In each cycle participants will:
Get nivolumab through a small plastic tube in the arm on Day 1.
Take tadalafil by mouth 1 time every day.
Take vancomycin by mouth 4 times a day. They will take it every day for weeks 1 3, then not take it for week 4.
Complete a medicine diary of dates, times, missed doses and symptoms.
Throughout the study, participants will repeat screening tests and will give stool samples or rectal swabs.
After their last cycle, participants will have 3 follow-up visits over 3 months. Then they will be contacted every 6 months by phone or email and asked about their general well-being.
|Condition or disease||Intervention/treatment||Phase|
|Heptocellular Carcinoma Heptocellular Cancer Metastatic Pancreatic Cancer Metastatic Colorectal Cancer Liver Metastasis||Drug: nivolumab Drug: tadalafil Drug: oral vancomycin||Phase 2|
- Current treatment options for patients with liver cancers, including hepatocellular carcinoma(HCC) and advanced liver cancers are limited and take no account of the known biological and genetic heterogeneity in these diseases. Median survival for advanced disease remains poor at approximately 1 year.
- Nivolumab is a fully human monoclonal immunoglobulin G4 (IgG4) antibody that is specific for human programmed death-1 (PD-1, cluster of differentiation 279 [CD279]) cell surface membrane receptor. Nivolumab has been approved by FDA for the treatment of HCC and other solid tumors.
- Tadalafil is a phosphodiesterase type 5 (PDE5) inhibitor which have been approved by the FDA for the treatment of pulmonary arterial hypertension, benign prostatic hyperplasia and erectile dysfunction, with a relative safe clinical profile. PDE5 inhibitors have been examined in multiple malignancies and cancer cell lines for their direct anticancer activities, for their
efficacy as chemo-sensitizers and for cancer chemoprevention.
- Oral vancomycin is antibiotic that has effect on altering gut commensal bacteria subsequently inducing a liver-selective anti-tumor effect.
- The aim of the study is to evaluate whether the immunomodulatory effect induced by PDE5 inhibitor and oral vancomycin can be enhanced by immune checkpoint inhibition in advanced liver cancer.
-To determine the Best Overall Response (BOR) according to Response Evaluation Criteria (RECIST 1.1) to combined treatment of nivolumab, oral vancomycin and tadalafil in patients with refractory primary HCC or liver dominant metastatic cancer from colorectal cancer (CRC) or pancreatic adenocarcinoma (PDAC).
- Histologically confirmed, hepatocellular carcinoma (HCC) Or
- Histologically confirmed carcinoma highly suggestive of a diagnosis of HCC Or
- Histologically confirmed advanced colorectal or pancreatic malignancy with liver involvement as dominant site of metastasis
- Measurable lesion, accessible for biopsy.
- Age greater than or equal to 18 years
- ECOG less than or equal to 1
- Acceptable renal, bone marrow and liver function.
- Willingness to undergo two mandatory tumor biopsies.
- The proposed study is a phase II study of combined nivolumab, oral vancomycin and tadalafil treatment in patients with HCC or liver dominant metastatic cancer from colorectal or pancreatic cancers.
- Treatment will be delivered in cycles consisting of 4 weeks (+/- 3 days) until progression or unacceptable toxicity.
Patients will be seen in Clinical Center on monthly basis with disease status evaluation every
8 (+/-1) weeks after start of study therapy.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||27 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of Nivolumab (Anti-PD1), Tadalafil and Oral Vancomycin in Patients With Refractory Primary Hepatocellular Carcinoma or Liver Dominant Metastatic Cancer From Colorectal or Pancreatic Cancers|
|Actual Study Start Date :||June 5, 2019|
|Estimated Primary Completion Date :||December 31, 2022|
|Estimated Study Completion Date :||December 31, 2022|
Experimental: 1/ Arm 1
Nivolumab, tadalafil and oral vancomycin
480 mg IV every 4 weeks
10 mg PO daily
Drug: oral vancomycin
125 mg every 6-hour (500 mg total daily dose) PO from week 1 to week 3, week 4 off.
- Best Overall Response (BOR) [ Time Frame: every 2 months ]Changes in tumor size and occurrence of metastases
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): NCT03785210
|Contact: Donna M Hrones, C.R.N.P.||(240) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center||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)|