Perioperative Therapy for Resectable and Borderline-Resectable Pancreatic Adenocarcinoma With Molecular Correlates

NCT02723331 | Completed Phase 2 Results DMC

• 1 other identifier: 15-0150.cc
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 4

Brief Summary

The objective of this study is to estimate the R0 resection rate in patients with Resectable Pancreatic Ductal Adenocarcinoma (R-PDAC) as well as those with Resectable Pancreatic Ductal Adenocarcinoma (BR-PDAC) independently in response to neoadjuvant sequential therapy of combination nab-paclitaxel and gemcitabine followed by stereotactic body radiotherapy (SBRT).

Conditions

Pancreatic Cancer; Pancreatic Adenocarcinoma; Pancreas Ductal Adenocarcinoma

Keywords

Stereotactic Body Radiation Therapy; Perioperative Therapy; Resectable Pancreas Ductal Adenocarcinoma; Borderline Resectable Pancreas Ductal Adenocarcinoma; Nab-paclitaxel; Abraxane; Gemcitabine; Neoadjuvant Therapy; Adjuvant Therapy

Outcome Measures

Primary Outcomes (1)

• R0 Resection Rates in Each Cohort as Measured by Macroscopically Complete Tumor Removal With Negative Microscopic Surgical Margins

  R0 resection rates will be measured in patients with resectable PDAC and with patients with borderline-resectable PDAC, independently in response to neoadjuvant sequential therapy of combination of nab-paclitaxel and gemcitabine and SBRT, as perioperative therapy. R0 resection is determined by macroscopically complete tumor removal with negative microscopic surgical margins in the bile duct, pancreatic parenchyma, and superior mesenteric artery (SMA).

  at the time of surgery

Secondary Outcomes (2)

• Number of Participants With Treatment Related Adverse Events as Assessed by CTCAE v.4.03

  24 months

• Median Overall Survival

  Up to 74 months

Study Arms (2)

Nab-paclitaxel and Gemcitabine for R-PDAC

EXPERIMENTAL

Nab-paclitaxel and gemcitabine, for R-PDAC patients enrolled in this trial, will be given in combination as neoadjuvant combination chemotherapy, followed by SBRT. This is will be followed up by surgical resection and an additional combination chemotherapy of nab-paclitaxel and gemcitabine as adjuvant chemotherapy.

Drug: Nab paclitaxel; Drug: Gemcitabine

Nab-paclitaxel and Gemcitabine for BR-PDAC

EXPERIMENTAL

Nab-paclitaxel and gemcitabine, for BR-PDAC patients enrolled in this trial, will be given in combination as neoadjuvant combination chemotherapy, followed by SBRT. This is will be followed up by surgical resection and an additional combination chemotherapy of nab-paclitaxel and gemcitabine as adjuvant chemotherapy.

Drug: Nab paclitaxel; Drug: Gemcitabine

Interventions

Nab paclitaxel DRUG

Nab-paclitaxel and gemcitabine, for R-PDAC patients, will be given in combination as neoadjuvant and adjuvant chemotherapy. Nab-paclitaxel will be administered by IV infusion at a dose of 125 mg/m2 over 30 minutes on Days 1, 8, and 15 of every 28-day cycle. Gemcitabine will be administered by IV infusion, immediately after the administration of nab-paclitaxel, at a dose of 1000 mg/m2 over 30 minutes on Days 1, 8 and 15 of every 28-day cycle.

Also known as: Abraxane

Nab-paclitaxel and Gemcitabine for BR-PDAC; Nab-paclitaxel and Gemcitabine for R-PDAC

Gemcitabine DRUG

Nab-paclitaxel and gemcitabine, for BR-PDAC patients, will be given in combination as neoadjuvant and adjuvant chemotherapy. Nab-paclitaxel will be administered by IV infusion at a dose of 125 mg/m2 over 30 minutes on Days 1, 8, and 15 of every 28-day cycle. Gemcitabine will be administered by IV infusion, immediately after the administration of nab-paclitaxel, at a dose of 1000 mg/m2 over 30 minutes on Days 1, 8 and 15 of every 28-day cycle.

Also known as: Gemzar

Nab-paclitaxel and Gemcitabine for BR-PDAC; Nab-paclitaxel and Gemcitabine for R-PDAC

Eligibility Criteria

• Age: 18 Years - 101 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed resectable or borderline resectable pancreatic adenocarcinoma.
• No evidence of distant metastasis representing stage IV metastatic disease.
• R-PDAC: No evidence of distant metastasis and tumor mass showing no extension to superior mesenteric artery (SMA) and hepatic artery. There must be a clearly defined fat plane between SMA and celiac axis. Patent superior mesenteric vein (SMV/portal vein (PV) with no distortion of venous architecture.
• BR-PDAC: defined as localized PDAC with 1 or more of the following features: a) an interface between the primary tumor and superior mesenteric vein (SMV)-portal vein (PV) measuring 180o or greater of the circumference of the vein wall, and/or b) short-segment occlusion of the SMV-PV with normal vein above and below the level of obstruction that is amenable to resection and venous reconstruction and/or c) short-segment interface of any degree between tumor and hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and arterial reconstruction and/or d) an interface between the tumor and SMA or celiac trunk measuring less than 180o of the circumference of the artery wall.
• Age \> 18 years old
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Patients must have adequate bone marrow function:
• Platelets \>100,000 cells/mm3
• Hemoglobin \> 9.0 g/dL
• Absolute Neutrophil Count \> 1,500 cells/mm3
• Patients must have adequate liver function:
• aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT) \< 2.5 X upper limit of normal
• Alkaline phosphatase \< 2.5 X upper limit of normal, unless bone metastasis is present in the absence of liver metastasis
• Total bilirubin \< 1.5 mg/dL
• Patients must have adequate renal function: creatinine \<1.5 mg/dL is recommended; however, institutional norms are acceptable. Creatinine within institutional limits of normal or creatinine clearance (CrCl) \> 50 mL/min calculated using the Cockcroft-Gault equation.

You may not qualify if:

• Patients with locally advanced surgically unresectable PDAC.
• Patients with evidence of distant metastatic PDAC.
• Prior chemotherapy or radiation therapy of any kind for treatment of pancreas adenocarcinoma.
• Prior major surgery within 4 weeks of starting study drug administration.
• Patient unable or not willing to perform all study related biopsies and blood draws for exploratory endpoints will not be enrolled on study as all study related procedures are mandatory.
• Concomitant treatment with full dose warfarin (coumadin) is NOT allowed. However, treatment with low molecular weight heparin (LMWH) (such as enoxaparin or dalteparin) or rivaroxaban is allowed. Patients on full dose warfarin (coumadin) must be transitioned to either LMWH or rivaroxaban prior to administration of any study related drugs.
• Recent or ongoing clinically significant gastrointestinal disorder (e.g., malabsorption, bleeding, inflammation, emesis, diarrhea \>grade 1).
• Patients with clinically significant cardiac disease (New York Heart Association Classification III or IV and cardiac arrhythmias not well controlled with medication), or myocardial infarction within the previous six months.
• Serious, uncontrolled, concurrent infection(s) requiring antibiotics.
• Pregnant or breastfeeding women: positive pregnancy test within 7 days of starting treatment.
• Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cervical cancer.
• Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
• Patients with external biliary drains.

Sponsors & Collaborators

• Academic Thoracic Oncology Medical Investigators Consortium: lead
• Celgene Corporation: collaborator
• Criterium, Inc.: collaborator
• University of Colorado, Denver: collaborator

Study Sites (4)

Mayo Clinic Hospital

Scottsdale, Arizona, 85259, United States

Location

University of Arizona

Tucson, Arizona, 85724, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

New York University

New York, New York, 10012, United States

Location

Related Publications (1)

• Cohen DJ, Goldberg JD, Leichman L, Hochman T, Newman E, Du K, Megibow A, Oberstein P, Al-Rajabi R, Scott AJ, Bekaii-Saab T, Messersmith WA, Weekes C. Perioperative therapy for resectable and borderline resectable pancreatic adenocarcinoma: an Academic Gastrointestinal Cancer Consortium Study. Oncologist. 2025 Oct 1;30(10):oyaf271. doi: 10.1093/oncolo/oyaf271.

  PMID: 40972532 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Taxes; Albumin-Bound Paclitaxel; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Economics; Health Care Economics and Organizations; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Wells Messersmith, MD
• Organization: University of Colorado Hospital

wells.messersmith@cuanschutz.edu

303-724-0747

Study Officials

• Wells Messersmith, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2016
• First Posted: March 30, 2016
• Study Start: December 30, 2016
• Primary Completion: December 8, 2022
• Study Completion: December 28, 2022
• Last Updated: July 1, 2025
• Results First Posted: February 14, 2024

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)