Adaptive Approach to Neoadjuvant Therapy to Maximize Resection Rates for Pancreatic Adenocarcinoma

NCT04594772 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: UCCC-GI-20-02
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine if neoadjuvant therapy to increases resection rate for pancreatic adenocarcinoma.

Conditions

Pancreas Cancer

Outcome Measures

Primary Outcomes (1)

• Measuring the proportion of patients undergoing surgical resection using historical data compared to 32 patients in current study.

  Using historical data from prospective trials and meta-analysis of multiple smaller studies, the expected proportion of patients undergoing resection in a mixed population of resectable and borderline resectable cancers is approximately 60%. We ambitiously aim to increase this to 80% or higher. With a one-sided of 0.05 and power of 80%, we will need 32 patients to demonstrate this difference.

  16 months

Secondary Outcomes (7)

• Measuring the proportion of patients switching chemotherapy at interim assessment versus those not switching chemotherapy regimen at interim assessment.

  16 months

• Measuring Disease-free survival after resection calculated as time from surgical resection to either disease recurrence or death, whichever comes first.

  5 years

• Overall survival will be calculated as time from registration on study to death. For survival time calculation, the Kaplan-Meier method will be used, and if the endpoint is not reached, the cases will be censored.

  5 years

• Measuring the Radiologic response (using RECIST 1.1) to neoadjuvant therapy

  5 years

• Measuring the Pathologic response to neoadjuvant therapy as Complete Response, Partial Response, Progressive Disease, or Stable Disease.

  5 years

Study Arms (1)

Neoadjuvant therapy

EXPERIMENTAL

All patients will receive Neoadjuvant therapy.

Drug: Folfirinox; Drug: Gemcitabine; Radiation: radiation therapy; Procedure: Pancreatectomy

Interventions

Folfirinox DRUG

Chemotherapy will begin with FOLFIRINOX - a standard regimen used in pancreatic cancer treatment, consisting of 5-fluorouracil (2400 mg/m2), irinotecan (180 mg/m2) and oxaliplatin (85 mg/m2). Treatment will continue for 2 cycles (4 doses), and then re-evaluation will be performed. If a decision to continue with FOLFIRINOX is made, it will be administered for another 4 cycles (8 doses).

Also known as: 5-fluorouracil, irinotecan and oxaliplatin

Neoadjuvant therapy

Gemcitabine DRUG

At the first planned analysis, if a switch is indicated based on prespecified criteria , gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) - another standard regimen in this setting - will be used. It will be administered for 4 cycles (12 doses).

Also known as: gemcitabine and nab-paclitaxel

Neoadjuvant therapy

radiation therapy RADIATION

Radiation therapy may be used prior to surgery, based on findings on the final pre-operative scan per standard of care. Radiation therapy will be delivered in patients with artery and venous involvement meeting the Intergroup definition for borderline resectable disease. Radiotherapy will be delivered via a hypofractionated approach over 10 fractions and will include target volumes to the primary tumor and elective coverage of vascular structures at risk. Radiation will be delivered with concurrent chemotherapy.

Neoadjuvant therapy

Pancreatectomy PROCEDURE

Pancreatectomy should occur within 4 to 8 weeks after the last dose of preoperative chemotherapy. Staging laparoscopy may be performed at the time of planned laparotomy but is not required. Either standard or pylorus-preserving pancreaticoduodenectomy, distal subtotal pancreatectomy, or total pancreatectomy may be performed. Surgical drains and enteral tubes (e.g. gastrostomy and/or jejunostomy tubes) may be placed at the discretion of the operating surgeon.

Neoadjuvant therapy

Eligibility Criteria

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

You may qualify if:

• Diagnosis of pancreatic carcinoma or adenocarcinoma confirmed by tissue. Histologies other than carcinoma or adenocarcinoma are not allowed.
• Resectable or borderline resectable primary tumor, evaluated on a baseline contrast-enhanced CT or MRI scan (CT Chest/Abdomen/Pelvis with contrast is preferred; if MRI used at baseline, then follow up with MRI as well), and defined using Intergroup criteria:
• Tumor vessel wall interface 0-360 for portal and superior mesenteric veins.
• Tumor vessel wall interface \<180 for celiac, common hepatic, and superior mesenteric arteries.
• No suspicious metastatic lesions (no visceral lesions, no enlarged nodes outside the surgical basin).
• Age ≥18 years.
• ECOG performance status ≤ 1.
• No prior therapy for index pancreatic cancer.
• Patients must have adequate organ and marrow function as defined in protocol
• Known human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Patients with a prior malignancy (with all treatment completed at least 2 years prior to enrollment) whose natural history does not have the potential to interfere with the safety or efficacy assessment of this study are eligible.
• Women of child-bearing potential and fertile men must agree to use adequate contraception (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of active treatment.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Patients with uncontrolled intercurrent illness or comorbidities that would, in the opinion of the treating physician, prevent receipt of standard of care chemotherapy, radiation or surgery.
• Pregnant women or women who are breastfeeding are excluded from this study.
• Patients who are currently receiving any other investigational agents. Patients who have received other investigational agents previously who are no longer receiving these investigational agents may be eligible at the discretion of the PI.
• Patients with psychiatric illness/social situations that would limit compliance with study requirements, per the PI's discretion.
• Patients who, in the opinion of the PI, will be unable to adhere to study requirements.

Sponsors & Collaborators

• University of Cincinnati: lead

Study Sites (2)

University of Arizona

Tucson, Arizona, 85724, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

folfirinox; Fluorouracil; Irinotecan; Oxaliplatin; Gemcitabine; 130-nm albumin-bound paclitaxel; Radiotherapy; Pancreatectomy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Therapeutics; Digestive System Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Davendra Sohal, Sohal

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 13, 2020
• First Posted: October 20, 2020
• Study Start: March 17, 2021
• Primary Completion: June 13, 2025
• Study Completion: January 1, 2026
• Last Updated: July 2, 2025

Record last verified: 2025-07

Locations

US (2)