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Cancer, Hypoxia, and Metabolism · Journal article
Cancer Research Communications · August 10, 2026
Early or partial results. Treat as a signal, not a conclusion.
This is a pilot feasibility and safety study of paricalcitol combined with multiagent chemotherapy and nivolumab in resectable pancreatic cancer, enrolling only 3 patients but confirming tolerability. Preclinical work in 140 KPC mice demonstrates that NGC chemotherapy reduces FAP and increases collagen but induces chemoresistance features (epithelial-mesenchymal transition, reduced perfusion), and suggests that calcipotriol or losartan may mitigate these effects through distinct stromal mechanisms.
Pilot randomized clinical trial with integrated preclinical randomized mouse study. Clinical: patients with resectable epithelial-subtype PDAC enrolled in pilot trial NCT03519308. Preclinical: genetically engineered KPC mice.. Intervention: Clinical: weekly paricalcitol infusion combined with NGC chemotherapy and nivolumab. Preclinical: NGC chemotherapy, NGC plus calcipotriol (synthetic vitamin D), or NGC plus losartan.. Compared with: Clinical: NGC plus nivolumab without paricalcitol (though N too small to evaluate). Preclinical: NGC monotherapy.. Not stated..
Clinical trial enrolled N=3 patients; confirmed safety and feasibility of weekly paricalcitol with NGC chemotherapy and nivolumab NGC monotherapy induced remarkable reduction in FAP level and significant increase in matrix collagen content NGC chemotherapy significantly reduced blood perfusion and capillary density and activated epithelial mesenchymal transition
Clinical trial severely underpowered (N=3); no efficacy endpoint reported, only feasibility and safety Clinical trial enrolled N=3 patients; confirmed safety and feasibility of weekly paricalcitol with NGC chemotherapy and nivolumab
The clinical safety signal from N=3 is reassuring but does not establish efficacy; the preclinical mechanistic findings suggest a rational basis for further investigation of stromal-targeted combination therapy in PDAC, but require validation in larger controlled trials before clinical translation.
A pilot clinical trial with critically limited enrollment (N=3) that confirms safety and feasibility but cannot establish efficacy; accompanied by mechanistic preclinical work in a mouse model.
As stated by the source record.
Quoted from the source exactly as published.
The clinical safety signal from N=3 is reassuring but does not establish efficacy; the preclinical mechanistic findings suggest a rational basis for further investigation of stromal-targeted combination therapy in PDAC, but require validation in larger controlled trials before clinical translation.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Abstract Purpose: A pilot clinical trial (NCT03519308) was conducted to evaluate perioperative chemotherapy (nab-paclitaxel, gemcitabine, and cisplatin; NGC) plus nivolumab, with or without synthetic vitamin D (paricalcitol) in resectable pancreatic ductal adenocarcinoma (PDAC). Preclinical studies were designed with statistical power to match the clinical trial treatment and compare NGC only versus NGC plus synthetic vitamin D (calcipotriol) or losartan (an antihypertensive medication). Experimental Design: Molecular subtyping was applied to enroll patients with epithelial subtype PDAC. Genetically engineered PDAC model (KPC mice, N=140) were randomized to NGC only and combined therapies. Multiparametric MRI and molecular profiling were integrated to assess treatment-induced effects on stroma, including capillary perfusion and density, matrix collagen content, fibroblast activation protein (FAP) level and transcriptome changes. Results: The clinical trial had limited enrollment (N=3) but confirmed the safety and feasibility of weekly paricalcitol infusion in combination with multiagent chemotherapy. NGC chemotherapy had a profound impact on stroma, inducing a remarkable reduction in FAP level accompanied by a significant increase in matrix collagen content; chemotherapy also activated epithelial mesenchymal transition and reduced blood perfusion and capillary density significantly, resulting in features of chemoresistance. Combining NGC with stromal-targeting agents—Calcipotriol or Losartan— diminished epithelial-to-mesenchymal transition and partially restored perfusion through distinct mechanisms: Calcipotriol activates vitamin D receptor to reprise a quiescent stroma while Losartan suppresses TGFβ to increase lymphocyte infiltration. Conclusion: These findings support further investigations of stromal-directed combination strategies to overcome chemotherapy-induced resistance of PDAC. DCE-MRI may provide a valuable platform to monitor stromal adaptations to therapy in vivo.
Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.