PDAC Regression and Intraoperative Surgical Margin With Neoadjuvant TAMP (PRISM-TAMP)

Summary

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival outcomes, even when treated with modern chemotherapy and radiation. Patients with borderline resectable PDAC often receive neoadjuvant systemic therapy to improve the likelihood of successful surgical removal of the tumor, but rates of incomplete tumor regression and positive surgical margins remain high. This Phase Ib/II, single-arm study evaluates the safety and feasibility of adding trans-arterial microperfusion (TAMP) delivery of gemcitabine to standard neoadjuvant therapy for patients with borderline resectable PDAC. In this study, patients receive standard systemic chemotherapy with modified FOLFIRINOX followed by stereotactic body radiation therapy (SBRT). After completion of chemoradiation, gemcitabine is delivered directly to the tumor through the arterial blood supply using the RenovoCath® catheter system. Gemcitabine is an FDA-approved chemotherapy drug for pancreatic cancer, and the study is evaluating a novel method of delivering the drug rather than a new medication. The primary objective of the study is to assess the safety and tolerability of neoadjuvant TAMP-delivered gemcitabine in this treatment setting. Secondary objectives include evaluation of surgical margin status and pathologic tumor regression following surgical resection. Exploratory analyses will examine relapse-free survival. Results from this study will help determine whether this locoregional chemotherapy approach can be safely integrated into neoadjuvant treatment strategies for patients with borderline resectable PDAC.

Interventions

• Gemcitabine Delivered by Transarterial Microperfusion · COMBINATION_PRODUCT

  Gemcitabine is administered via transarterial microperfusion using an arterial infusion catheter system to deliver chemotherapy directly to the pancreatic tumor bed. Following completion of neoadjuvant systemic chemotherapy with modified FOLFIRINOX and stereotactic body radiation therapy, gemcitabine is infused intra-arterially at a dose of 1000 mg/m² under controlled pressure conditions. The intervention evaluates the safety and feasibility of this locoregional drug delivery approach in the neoadjuvant setting.

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

Inclusion Criteria:

* Histologically confirmed pancreatic ductal adenocarcinoma (PDAC).
* Borderline resectable disease as defined by the ABC classification criteria, incorporating one or more of the following:

  * Anatomy (A): Vascular involvement consistent with borderline resectable or resectable locally advanced-PDAC (e.g., abutment of the superior mesenteric vein or artery, portal vein, or celiac axis) as determined by cross-sectional imaging
  * Biology (B): Concern for extra-pancreatic metastasis or known N1 disease or suspicious but nonconfirmatory liver/lung lesion(s). CA19-9\>500 after normalized bilirubin
  * Condition (C): Functional status and comorbidity profile adequate for curative-intent surgery, as assessed by the multidisciplinary team, specifically WHO PS \>/=1.
* No prior treatment for PDAC (e.g., chemotherapy, radiation, or surgery).
* Age ≥ 18 years.
* ECOG performance status of 0 or 1.
* Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

* Locally Advanced PDAC or metastatic PDAC
* Histology other than adenocarcinoma
* Non-accessible arterial anatomy
* Gemcitabine hypersensitivity or contraindication to mFOLFIRINOX therapy based on provider assessment

Sites (1)

• University of Vermont Medical Center, Burlington, Vermont