Evidence map›Paper›PMID 40789510›Full record

Trial reportCancer letters2025

Altering the gut microbiome and tumor microenvironment in advanced liver cancer: A phase II study of nivolumab, tadalafil and oral vancomycin in patients with refractory primary hepatocellular carcinoma or liver dominant metastatic cancer from colorectal or pancreatic cancers.

Chi Ma, Joy A Awosika, Cecilia Monge, Kelley Coffman-D'Annibale, Changqing Xie, Nebojsa Skorupan, Donna M Hrones, Meng Liu, Lichun Ma, Bradford J Wood and 8 more

Abstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cancer letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Chi MaThoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
Joy A AwosikaThoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
Cecilia MongeThoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
Kelley Coffman-D'AnnibaleThoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
Changqing XieThoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
Nebojsa SkorupanThoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
Donna M HronesThoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
Meng LiuCancer Data Science Laboratory, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
Lichun MaCancer Data Science Laboratory, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
Bradford J WoodCenter for Interventional Radiology, Radiology and Imaging Sciences, NIH Clinical Center & Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
Elliot B LevyCenter for Interventional Radiology, Radiology and Imaging Sciences, NIH Clinical Center & Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
David E KleinerLaboratory of Pathology, Center for Cancer Research (CCR), National Cancer Institute, National Institutes of Health, Bethesda, Maryland NIH, Bethesda, USA.
William D FiggMolecular Pharmacology Section, Center for Cancer Research (CCR), National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Bernadette ReddRadiology and Imaging Sciences, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
John A McCullochGenetics and Microbiome Core, Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Miriam R FernandesCancer Immunobiology Section, Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Giorgio TrinchieriCancer and Inflammation Program, Center for Cancer Research (CCR), National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Cancer Immunobiology Section, Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Tim F GretenThoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA; Liver Cancer Program, Center for Cancer Research (CCR), National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: tim.greten@nih.gov.

Funding

Clinical protocols for the treatment of GI cancerZIABC011343 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GRETEN, TIM · 2010 to 2025
$4.8M
Intramural NIH HHS Z99 CA999999Intramural NIH HHS ZIA BC011343
6 · The paper itself

Abstract

A phase II study was conducted in patients with primary hepatocellular carcinoma or liver dominant metastatic cancer from colorectal (CRC) or pancreatic (PDAC) cancers to assess the effect of nivolumab (anti-PD1), oral vancomycin and tadalafil. Patients were treated with 480 mg nivolumab intravenously every 4 weeks, oral 10 mg tadalafil daily and 125 mg vancomycin orally every 6 h days 1-21 of a 28-day cycle. The primary endpoint was best overall response. Secondary endpoints included analysis of the gut microbiota, serum bile acids and immune cells in peripheral blood. A total of 22 patients were enrolled (6 HCC, 7 CRC and 9 PDAC patients). Three out of 16 evaluable patients (2 patients with HCC and 1 patient with CRC) demonstrated stable disease as best response. No unexpected adverse events were observed. A decrease in secondary bile acids along with changes in gut microbiota were observed. Vancomycin/Tadalafil/Nivolumab treatment did not cause any apparent change of major immune cell frequencies in peripheral blood however, a significant change was observed in monocyte subsets. Treatment was well tolerated and led to changes in the gut microbiome along with changes in the bile acid pool and myeloid cells in peripheral blood. No clinical activity was observed.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsCarcinoma, HepatocellularColorectal NeoplasmsGastrointestinal MicrobiomeLiver NeoplasmsPancreatic NeoplasmsTumor MicroenvironmentAdministration, OralAdultAgedFemaleHumansMaleMiddle AgedNivolumabTadalafilNivolumabTadalafilVancomycinBile acid metabolismGut microbiomeHepatocellular carcinomaImmunomodulationLiver metastasesMyeloid-derived suppressor cellsNatural killer T cellsRegulatory T cellsTumor-associated macrophagesTumor microenvironment

Identifiers

PMID40789510
PMCPMC13463197

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.