Nivolumab (Anti-PD1), Tadalafil and Oral Vancomycin in People With Refractory Primary Hepatocellular Carcinoma or Liver Dominant Metastatic Cancer From Colorectal or Pancreatic Cancers

Stopped early · Phase 2

Conditions studied: Hepatocellular Carcinoma, Hepatocellular Cancer, Metastatic Pancreatic Cancer, Metastatic Colorectal Cancer, Liver Metastasis

In brief

Background: 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. Objective: To investigate if nivolumab given with tadalafil and vancomycin causes liver cancer to shrink. Eligibility: 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 Design: Participants will be screened with: Medical and cancer history Review of symptoms and ability to perform normal activities Physical exam 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. ...

Key facts

Study ID

NCT03785210

Run by

National Cancer Institute (NCI)

People needed

22

Starts

2019-06-05

Expected to finish

2022-12-31

Last updated by the study team

2026-02-23

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Patients who have had standard-of-care anti-cancer therapy or therapy with investigational agents (e.g., chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies or other investigation agents), large field radiotherapy, or major surgery within 4 weeks prior to enrollment.
• Therapy with antibiotics within 30 days prior to enrollment.
• Therapy with nitrates, alpha-blockers, or cytochrome P450 (CYP3A4) inhibitors within 7- days prior to enrollment and for whom stopping is unsafe and/or a safe substitute is not medically recommended. Use of PDE5 inhibitors such as vardenafil (Levitra), tadalafil (Cialis), and sildenafil citrate (Viagra) less than or equal to 15-days prior to enrollment.
• The patient must not be currently on a corticosteroid dose greater than physiologic replacement dosing defined as 10 mg of cortisone per day or its equivalent.
• For PDAC patients with liver metastases, primary PDAC has not been resected (unless the primary is in the tail of the pancreas).
• Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Have signs of liver failure, e.g., clinical significant ascites, encephalopathy, or variceal bleeding within 6 months prior to enrollment.
• Prior major liver resection: remnant liver <50% of the initial liver volume. Patients with a biliary stent can be included.
• Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome or Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), myasthenia gravis; systemic autoimmune disease such as Systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome. Such diseases should be excluded because of the risk of recurrence or exacerbation of disease.
• Of note, patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.
• Have history of idiopathic pulmonary fibrosis (including bronchiolitis obliterans with organizing pneumonia) or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with myocardial infarction or myocarditis within 12 months prior to enrollment.
• History of severe or unstable cerebrovascular disease.
• Sustained hypotension (<90/50 mmHg) or uncontrolled hypertension (>160/100 mmHg)
• Stroke within 6 months prior to enrollment.
• Human immunodeficiency virus (HIV)-positive patients are excluded because HIV causes complicated immune deficiency and study treatment can possess more risks for these patients.
• Have had prior transplant of any kind.
• Have ascites.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab, tadalafil or vancomycin.
• History of severe hypersensitivity reaction to any monoclonal antibody.
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years prior to enrollment.
• Pregnant women are excluded from this study because nivolumabs potential for teratogenic or abortifacient effects is unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with nivolumab, breastfeeding should be discontinued if the mother is treated with nivolumab

Where it is running

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.