ArticlePancreas2016
A Phase I Study of FOLFIRINOX Plus IPI-926, a Hedgehog Pathway Inhibitor, for Advanced Pancreatic Adenocarcinoma.
Article in Pancreas, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
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Who cites it
139 citing papers in PubMed, 1 synthesis or guideline pooled it, 219 citations in OpenAlex.
- Therapies Targeting the Tumor Stroma and the VEGF/VEGFR Axis in Pancreatic Ductal Adenocarcinoma: a Systematic Review and Meta-Analysis.Targeted oncology · 2018Pooled it
- Trial
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- DeCAF defines clinical fibroblast subtypes and multidimensional tumor-stroma crosstalk shaping prognosis and immunotherapy response.Cell reports. Medicine · 2026Article
- Novel anti-tumor strategies: targeting the crosstalk between cancer stem cells and cancer-associated fibroblasts to resist drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Cancer-associated fibroblasts at the crossroads of tumor progression and therapy resistance: from heterogeneity to precision reprogramming.Journal of the Egyptian National Cancer Institute · 2025Review
- Experimental models of pancreas cancer: what has been the impact for precision medicine?The Journal of clinical investigation · 2025Review
- Tissue mechanics in tumor heterogeneity and aggression.Trends in cancer · 2025Review
- Recent Advances in Nanotechnology-Based Approaches for Ferroptosis Therapy and Imaging Diagnosis in Pancreatic Cancer.Pharmaceutics · 2025Review
- The fibroinflammatory response in cancer.Nature reviews. Cancer · 2025Review
- Conserved spatial subtypes and cellular neighborhoods of cancer-associated fibroblasts revealed by single-cell spatial multi-omics.Cancer cell · 2025Article
- Review
- Cancer associated fibroblasts in cancer development and therapy.Journal of hematology & oncology · 2025Review
- Disrupting AGR2/IGF1 paracrine and reciprocal signaling for pancreatic cancer therapy.Cell reports. Medicine · 2025Article
- A practical distribution pattern of α-SMA-positive carcinoma associated fibroblasts indicates poor prognosis of patients with pancreatic ductal adenocarcinoma.Translational oncology · 2025Article
- TGF-β1/SMAD3-mediated Non-canonical Hedgehog Signaling Promotes Pancreatic Stellate Cell Activation and Fibrosis in Chronic Pancreatitis.International journal of biological sciences · 2025Article
- Targeting stromal components in pancreatic ductal adenocarcinoma: a review.Ecancermedicalscience · 2025Review
- Differential activity of MAPK signalling defines fibroblast subtypes in pancreatic cancer.Nature communications · 2024Article
- CAF-induced physical constraints controlling T cell state and localization in solid tumours.Nature reviews. Cancer · 2024Review
- Signaling pathways in liver cancer: pathogenesis and targeted therapy.Molecular biomedicine · 2024Review
79 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
objectivesIn mouse models of pancreatic cancer, IPI-926, an oral Hedgehog inhibitor, increases chemotherapy delivery by depleting tumor-associated stroma. This multicenter phase Ib study evaluated IPI-926 in combination with FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, oxaliplatin) in patients with advanced pancreatic cancer.
methodsPatients were treated with once-daily IPI-926 plus FOLFIRINOX. A 3 + 3 dose escalation design was used, with cohort expansion at the maximum tolerated dose. A subset of patients underwent perfusion computed tomography to assess changes in tumor perfusion.
resultsThe maximum tolerated dose was identified 1 dose level below standard FOLFIRINOX. Common treatment-related adverse events included liver function test abnormalities, neuropathy, nausea/vomiting, and diarrhea. Objective response rate was high (67%), and patients receiving IPI-926 maintenance showed further declines in CA19-9 levels even after FOLFIRINOX discontinuation. Treatment did not result in consistent increases in tumor perfusion. The study closed early when a separate phase II trial of IPI-926 plus gemcitabine indicated detrimental effects of this combination.
conclusionsThis is the first study to demonstrate the feasibility of using FOLFIRINOX as the chemotherapeutic backbone in a clinical trial design. Although robust antitumor activity and acceptable safety were observed with the addition of IPI-926 to this regimen, future development of Hedgehog inhibitors in pancreatic cancer seems unlikely.
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Registered trials
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.