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Preclinical rationale linked GLUT1-mediated dehydroascorbate uptake to oxidative stress and glutathione depletion, potentially benefiting KRAS-mutated cancers. Eligible patients received ascorbic acid at 25, 37.5, or 56.25 g/m2 twice weekly plus NABPLAGEM; the primary endpoint was maximum tolerated dose. Seventeen patients were enrolled; no MTD was reached and treatment was feasible at 56.25 g/m2 twice weekly. Safety reflected frequent grade ≥3 thrombocytopenia and anemia; efficacy signals for survival were 7.1 months PFS and 14.2 months OS without significant dose-dependent differences, and liver fat decreased in some imaging.",{"@graph":69,"@context":126},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/phase-ib-trial-of-high-dose-ascorbic-acid-nab-paclitaxel-cisplatin-gemcitabine-in-patients-with-untreated-metastatic-pancreatic-cancer/376415/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/phase-ib-trial-of-high-dose-ascorbic-acid-nab-paclitaxel-cisplatin-gemcitabine-in-patients-with-untreated-metastatic-pancreatic-cancer/376415.png","ImageObject",300,407,{"name":92,"@type":93},"awa","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118,122],{"name":109,"@type":110,"acceptedAnswer":111},"What was the main purpose of this Phase IB trial?","Question",{"text":112,"@type":113},"To determine the maximum tolerated dose (MTD) of high-dose intravenous ascorbic acid when combined with nab-paclitaxel, cisplatin, and gemcitabine in untreated metastatic pancreatic ductal adenocarcinoma.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What dosing schedule and patient criteria were used?",{"text":117,"@type":113},"Adults (≥18) with ECOG 0–1 and measurable PDAC with adequate organ function received ascorbic acid at 25, 37.5, or 56.25 g/m2 twice weekly plus NABPLAGEM on Days 1 and 8 of 21-day cycles.",{"name":119,"@type":110,"acceptedAnswer":120},"What did the trial find about safety and tolerability?",{"text":121,"@type":113},"No MTD was reached; ascorbic acid up to 56.25 g/m2 twice weekly was feasible. Grade ≥3 treatment-related adverse events included thrombocytopenia, anemia, neutropenia, and hypokalemia, with no significant differences between dose groups.",{"name":123,"@type":110,"acceptedAnswer":124},"Did high-dose ascorbic acid improve disease outcomes compared with historical chemotherapy?",{"text":125,"@type":113},"The trial did not improve disease response versus historical data for chemotherapy alone, with median progression-free survival of 7.1 months and overall survival of 14.2 months without significant differences by ascorbic acid dose.","https://schema.org",{"og:url":83,"og:type":128,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":130,"canonical":83},"index,follow",{"doc_id":132,"site_id":62},376415,1790519484,{"code":4,"msg":5,"data":135},{"doc_id":132,"user_id":136,"nickname":92,"user_avatar":137,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":138,"file_id":139,"file_url":140,"file_type":141,"file_size":142,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":143,"language":144,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":145,"faqs":146,"seo_title":147,"seo_description":67,"update_tm":148,"read_time":149},3985747858093,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Redox Biology 88 (2025) 103895  \nContents lists available at ScienceDirect  \nRedox Biology  \njournal [homepage:](homepage: www.elsevier.com/locate/redox)[ www.elsevier.com/locate/redox](homepage: www.elsevier.com/locate/redox)  \n| Phase IB trial of high dose ascorbic acid + nab-paclitaxel + cisplatin + gemcitabine in patients with untreated metastatic pancreatic cancer\u003Cbr>Gayle S. Jameson a , S. Danielle LeGranda, Michael S. Gordon a,f, Denise J. Roe b,\u003Cbr>Betsy C. Wertheimb, Kellen Olszewski c, Josh Rabinowitz c, Ron Evans d, Michael Downes d, Morgan Truittd, Ron Korne, Haiyong Han f, Richard M. Miller a, Michael T. Barrett g, David Propper h, Daniel D. Von Hoffa,f, Erkut Borazanci *,a\u003Cbr>a HonorHealth Research Institute, Scottsdale, AZ, USA\u003Cbr>b The University of Arizona Cancer Center, Tucson, AZ, USA\u003Cbr>c Ludwig Institute for Cancer Research, Princeton Branch, Princeton University, Princeton, NJ, USA d Salk Institute, La Jolla, CA, USA\u003Cbr>e Imaging Endpoints, Scottsdale, AZ, USA\u003Cbr>f Translational Genomics Research Institute (TGen), Part of City of Hope, Phoenix, AZ, USA g Mayo Clinic, Scottsdale, AZ, USA\u003Cbr>h Barts Cancer Institute, Queen Mary University of London, London, UK |  |\n| --- | --- |\n| A R T I C L E I N F O\u003Cbr>Keywords:\u003Cbr>Untreated metastatic pancreatic adenocarcinoma\u003Cbr>Ascorbic acid + nab-paclitaxel + cisplatin + gemcitabine\u003Cbr>Pancreatic ductal adenocarcinoma\u003Cbr>Clinical trial | A B S T R A C T\u003Cbr>Background: Preclinical studies suggest that cancer cells take up oxidized vitamin C (dehydroascorbate, DHA) via the GLUT1 transporter, leading to oxidative stress and glutathione depletion. This mechanism may offer a therapeutic strategy for KRAS-mutated cancers. This Phase IB trial evaluated high-dose intravenous ascorbic acid (AA) combined with nab-paclitaxel, cisplatin, and gemcitabine (NABPLAGEM) in patients with untreated metastatic pancreatic ductal adenocarcinoma (PDAC).\u003Cbr>Methods: Eligible patients (≥18 years, ECOG 0–1, measurable PDAC, adequate organ function) received AA (25, 37.5, or 56.25 g/m2 twice weekly) plus NABPLAGEM on Days 1 and 8 of 21-day cycles. The primary endpoint was determining the maximum tolerated dose (MTD) of AA.\u003Cbr>Results: Seventeen patients were enrolled (median age 63.9; 70.6 % female; 82.4 % white). No MTD was reached; AA up to 56.25 g/m2 twice weekly was feasible. Patients on the lowest AA dose remained on treatment longer. Grade ≥3 treatment-related adverse events (TRAEs) included thrombocytopenia (82.4 %), anemia (35.3 %), neutropenia (29.4 %), hypokalemia (29.4 %), diarrhea (11.8 %), and colitis (11.8 %), with no significant differences between dose groups. Peak AA levels >20 mM were achieved in 57 % of patients at the highest dose. Median progression-free survival (PFS) and overall survival (OS) were 7.1 and 14.2 months, respectively, with no significant differences by AA dose. Textural imaging showed decreased liver fat in 3 of 4 patients with baseline steatosis.\u003Cbr>Conclusion: High-dose AA with NABPLAGEM was tolerable in patients with advanced PDAC but did not improve disease response compared to historical data for chemotherapy alone. A separate study suggests AA may enhance gemcitabine and nab-paclitaxel efficacy without cisplatin. AA and cisplatin may have overlapping DNAdamaging effects, or differences in AA dosing frequency and exposure may influence outcomes - variables to consider in future trials.\u003Cbr>Trial registration: NCT03410030. |\n\n1. Introduction  \nPancreatic cancer is the third leading cause of cancer deaths in the U.  \nS., representing 8 % of all cancer deaths. In 2025, 67,440 new cases and 51,980 deaths are expected [1]. Most pancreatic ductal adenocarcinoma (PDAC) patients present with advanced or metastatic disease with a  \n* Corresponding author. 10510 N. 92nd Street Scottsdale, AZ 85258,, USA.  \nE-mail [address:](address: gjameson@HonorHealth.com)[ gjameson@HonorHealth.com](address: gjameson@HonorHealth.com) (G.S. Jameson).  \n[https://doi.org/10.1016/j","cbCaisq84BuaylUo","https://ap.wps.com/l/cbCaisq84BuaylUo","pdf",7453844,14,"English","# Background\n## Oxidized vitamin C uptake and redox mechanism\n# Methods\n## Eligibility criteria and treatment dosing\n## Primary endpoint\n# Results\n## Patient enrollment and dose feasibility\n## Treatment-related adverse events\n## Efficacy endpoints and imaging findings\n# Conclusion\n## Tolerability and lack of improved response versus historical chemotherapy\n# Trial Registration\n## NCT03410030","[{\"question\":\"What was the main purpose of this Phase IB trial?\",\"answer\":\"To determine the maximum tolerated dose (MTD) of high-dose intravenous ascorbic acid when combined with nab-paclitaxel, cisplatin, and gemcitabine in untreated metastatic pancreatic ductal adenocarcinoma.\"},{\"question\":\"What dosing schedule and patient criteria were used?\",\"answer\":\"Adults (≥18) with ECOG 0–1 and measurable PDAC with adequate organ function received ascorbic acid at 25, 37.5, or 56.25 g/m2 twice weekly plus NABPLAGEM on Days 1 and 8 of 21-day cycles.\"},{\"question\":\"What did the trial find about safety and tolerability?\",\"answer\":\"No MTD was reached; ascorbic acid up to 56.25 g/m2 twice weekly was feasible. Grade ≥3 treatment-related adverse events included thrombocytopenia, anemia, neutropenia, and hypokalemia, with no significant differences between dose groups.\"},{\"question\":\"Did high-dose ascorbic acid improve disease outcomes compared with historical chemotherapy?\",\"answer\":\"The trial did not improve disease response versus historical data for chemotherapy alone, with median progression-free survival of 7.1 months and overall survival of 14.2 months without significant differences by ascorbic acid dose.\"}]","Phase IB trial of high dose ascorbic acid - nab-paclitaxel - cisplatin - gemcitabine in patients with untreated metastatic pancreatic cancer | PDF",1790219058,35]