PurIST Classification-Guided Adaptive Neoadjuvant Chemotherapy by RNA Expression Profiling of EUS Aspiration Samples

NCT ID: NCT04683315

Last Updated: 2026-01-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-01
• Study Completion Date: 2028-12-31

Brief Summary

This is an open-label, phase II study in patients with resectable and borderline resectable pancreatic cancer.

Detailed Description

The study intervention involves molecular profiling Purity Independent Subtyping of Tumors (PurIST) subtyping of pretreatment Endoscopic Ultrasound Fine Needle Aspiration (EUS/FNA) samples to determine pancreatic cancer subtype. Neoadjuvant therapy is directed based on the molecular subtype (classical vs. basal). Patients with classical subtype will receive a standard chemotherapy (mFOLFIRINOX) and patients with basal subtype will receive an alternative standard therapy (gemcitabine/nab-paclitaxel).

Conditions

Pancreatic Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Subtype diagnosis and classification: Basal

Patients will be classified by (molecular) subtype (using the PurIST classifier) into two groups: basal and classical pancreatic cancer. Upon diagnosis, patients categorized as basal will receive two months of the Gemcitabine/Nab-paclitaxel Treatment Regimen.

Group Type: EXPERIMENTAL

Gemcitabine/Nab-paclitaxel Treatment Regimen

Intervention Type: DRUG

This regimen will be nab-paclitaxel and gemcitabine.

Subtype diagnosis and classification: Classical

Patients will be classified by (molecular) subtype (using the PurIST classifier) into two groups: basal and classical pancreatic cancer. Patients in the classical group will receive two months of the mFOLFIRINOX Treatment Regimen.

Group Type: EXPERIMENTAL

mFOLFIRINOX Treatment Regimen

Intervention Type: DRUG

This therapy will be 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX).

Basal Group: Restaging: Response to Treatment

After the first restaging evaluation, further treatment will be based on treatment response. Patients who demonstrate a response \[decline in carbohydrate antigen 19-9 (CA19-9) values\] and radiographic response, along with preserved performance status) will be maintained on the first line chemotherapy for an additional two months.

Group Type: EXPERIMENTAL

Gemcitabine/Nab-paclitaxel Treatment Regimen

Intervention Type: DRUG

This regimen will be nab-paclitaxel and gemcitabine.

Classical Group: Restaging: Response to Treatment

After the first restaging evaluation, further treatment will be based on treatment response. Patients who demonstrate a response \[decline in carbohydrate antigen 19-9 (CA19-9) values\] and radiographic response, along with preserved performance status) will be maintained on the first line chemotherapy for an additional two months.

Group Type: EXPERIMENTAL

mFOLFIRINOX Treatment Regimen

Intervention Type: DRUG

This therapy will be 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX).

Basal Group: Restaging: Patients with Stable Disease

Patients who do not have a significant decline in CA19-9 values will be changed to a second-line therapy for an additional two months.

Group Type: EXPERIMENTAL

mFOLFIRINOX Treatment Regimen

Intervention Type: DRUG

This therapy will be 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX).

Classical Group: Restaging: Patients with Stable Disease

Patients who do not have a significant decline in CA19-9 values will be changed to a second-line therapy for an additional two months.

Group Type: EXPERIMENTAL

Gemcitabine/Nab-paclitaxel Treatment Regimen

Intervention Type: DRUG

This regimen will be nab-paclitaxel and gemcitabine.

Basal Group: Restaging: Local Disease Progression

Further treatment will be based on treatment response. If the patient has local disease progression amenable to surgical resection, he or she will receive chemoradiation, rather than continued chemotherapy, so the window of opportunity for surgical resection is not lost.

Group Type: EXPERIMENTAL

Chemoradiation

Intervention Type: RADIATION

50.4 Gy in 28 fractions.

Classical Group: Restaging: Local Disease Progression

Further treatment will be based on treatment response. If the patient has local disease progression amenable to surgical resection, he or she will receive chemoradiation, rather than continued chemotherapy, so the window of opportunity for surgical resection is not lost.

Group Type: EXPERIMENTAL

Chemoradiation

Intervention Type: RADIATION

50.4 Gy in 28 fractions.

Interventions

mFOLFIRINOX Treatment Regimen

This therapy will be 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX).

Intervention Type: DRUG

Gemcitabine/Nab-paclitaxel Treatment Regimen

This regimen will be nab-paclitaxel and gemcitabine.

Intervention Type: DRUG

Chemoradiation

50.4 Gy in 28 fractions.

Intervention Type: RADIATION

Other Intervention Names

Fluorouracil; Folinic acid; Camptosar; Eloxatin; Gemzar; Abraxane

Eligibility Criteria

Inclusion Criteria

1. Have suspicion of pancreas adenocarcinoma and plan for endoscopic biopsy. Agrees to additional EUS biopsy to be performed at the first-restaging timepoint and tissue collection from surgical specimen.

2. Have a carbohydrate antigen 19-9 (CA19-9) level greater than 35 mg/dL regardless of total bilirubin level.

1. Be 18 years of age or older.

2. Be able to understand and provide written informed consent or have a legally authorized representative (LAR).

3. Have documentation of histologically confirmed adenocarcinoma. Biopsy must have been completed prior to start of treatment Have an Eastern Cooperative Group (ECOG) performance status < 2 (please see the appendix).

4. Have documentation of histologically confirmed adenocarcinoma. Biopsy must have been completed prior to start of treatment.

5. Have clinical stage consistent with resectable or borderline resectable adenocarcinoma of the pancreas, based on CT or MRI findings.

6. Have adequate organ and bone marrow function, as defined by

• total leukocytes >3 x103/μL.
• absolute neutrophil count (ANC) >1.5x 103/μL.
• hemoglobin >9 g/dL.
• platelets >100 x 10e3/μL.
• creatinine clearance >60 mL/min or creatinine <1.5 mg/dL.
• bilirubin < 2 mg/dL.
• aspartate transaminases (AST/SGOT) and alanine transaminases (ALT/SGPT) <3 x upper limit of normal (ULN). At two weeks from biliary decompression, if the subject's serum AST/ALT remains greater 3x ULN, but has demonstrated a progressive decline, the subject may be enrolled into the trial and appropriate modification and dose adjustments will be made to the assigned regimen. Eligibility of subjects whose AST/ALT remain elevated 3x ULN, without demonstrating a downward trend, will be determined at the discretion of the trial PIs.

7. Subjects must be CA19-9 producers as defined by a pretreatment CA 19-9 > 35 U/mL, when total bilirubin <2 mg/dL

8. Female patients must be postmenopausal (absence of menses for > 1 year), surgically sterile or have a negative pregnancy test and use at least one form of contraception for four weeks prior to Day 1 of the study, during study treatment and during the first four months after study treatment is discontinued. Male patients must be surgically sterile or use barrier contraception during the study and for four months after the last dose of any study drug.

Exclusion Criteria

1. Has received chemotherapy and/or radiation within three years prior to study enrollment.

2. Has any previous history of another malignancy (other than cured basal or squamous cell carcinoma of the skin or cured in situ carcinoma of the cervix or localized prostate cancer with normal prostate specific antigen) within three years of study enrollment.

3. Uncontrolled comorbidities including, but not limited to, ongoing or active serious infection, symptomatic congestive heart failure, unstable angina, unstable cardiac arrhythmias, psychiatric illness, excessive obesity (BMI >55) or situations that would limit compliance with the study requirements or the ability to willingly give written informed consent.

4. Known HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

5. Pregnant or breastfeeding patients or any patient with childbearing potential not using contraception four weeks prior to treatment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical College of Wisconsin

OTHER

Sponsor Role: lead

Responsible Party

Kathleen Christians

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kathleen K Christians, MD

Role: PRINCIPAL_INVESTIGATOR

Medical College of Wisconsin

Locations

HonorHealth Medical Group

Scottsdale, Arizona, United States

Site Status: RECRUITING

Froedtert & the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Medical College of Wisconsin Cancer Center Clinical Trials Office

Role: CONTACT

cccto@mcw.edu

866-680-0505 ext. 8900

Facility Contacts

Erkut Borazanci, MD

Role: primary

eborazanci@honorhealth.com

480-323-1350

Gayle Jameson, APNP

Role: backup

480-323-1350

Kathleen Christians, MD

Role: primary

kchristi@mcw.edu

414-955-1400

References

Li Y, Merker JD, Kshatriya R, Trembath DG, Morrison AB, Kuhlers PC, Rashid NU, Yeh JJ, Gulley ML. Purity Independent Subtyping of Tumors (PurIST) Pancreatic Cancer Classifier: Analytic Validation of a 16-RNA Expression Signature Distinguishing Basal and Classical Subtypes. J Mol Diagn. 2024 Nov;26(11):962-970. doi: 10.1016/j.jmoldx.2024.07.002. Epub 2024 Aug 22.

Reference Type: DERIVED

PMID: 39181325 (View on PubMed)

Other Identifiers

PRO00039451

Identifier Type: -

Identifier Source: org_study_id