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

Pancreatic Cancer Clinical Trial

— PANCREAS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04683315
• Other study ID #: PRO00039451
• Status: Recruiting
• Phase: Phase 2
• Start date: April 1, 2021
• Est. completion date: June 2027

Study information

• Verified date: October 2023
• Source: Medical College of Wisconsin
• Contact: Medical College of Wisconsin Cancer Center Clinical Trials Offic
• Phone: 866-680-0505
• Email: cccto[@]mcw.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 87
• Est. completion date: June 2027
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria (for Screening)

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. Inclusion Criteria (for Treatment)

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.

Related Conditions & MeSH terms

• Pancreatic Cancer

Intervention

Drug:
• mFOLFIRINOX Treatment Regimen
This therapy will be 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX).
• Gemcitabine/Nab-paclitaxel Treatment Regimen
This regimen will be nab-paclitaxel and gemcitabine.

Radiation:
• Chemoradiation
50.4 Gy in 28 fractions.

Locations

Country	Name	City	State
United States	Froedtert & the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	HonorHealth Medical Group	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Medical College of Wisconsin

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Subjects who receive PurIST classification-directed therapy.	The number of subjects who receive PurIST classification-directed therapy and have a treatment response following 12 weeks of therapy.	12 weeks
Secondary	Treatment response for subjects with basal subtype tumors.	The number of subjects with basal subtype tumors who have a treatment response.	12 weeks
Secondary	Treatment response for subjects with classical subtype tumors.	The number of subjects with classical subtype tumors who have a treatment response.	12 weeks
Secondary	Subjects with basal subtype tumors who complete all intended neoadjuvant therapy and surgical therapy.	The number of subjects completing all intended neoadjuvant therapy and surgical therapy.	One year
Secondary	Subjects with classical subtype tumors who complete all intended neoadjuvant therapy and surgical therapy.	The number of subjects completing all intended neoadjuvant therapy and surgical therapy.	One year