Clinical trial NCT04683315: PurIST Classification-Guided Adaptive Neoadjuvant Chemotherapy by RNA Expression Profiling of EUS Aspiration Samples
Official title: PurIST Classification-Guided Adaptive Neoadjuvant Chemotherapy by RNA Expression Profiling of EUS Aspiration Samples
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: molecular profiling
neoadjuvant
pancreatic adenocarcinoma
pancreas cancer
CA19-9
surgery
MCW
Lead sponsor: Medical College of Wisconsin
Sponsor class: OTHER
First posted: 2020-12-24
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Subjects who receive PurIST classification-directed therapy.
timeFrame: 12 weeks
Secondary outcomes:
measure: Treatment response for subjects with basal subtype tumors.
timeFrame: 12 weeks
measure: Treatment response for subjects with classical subtype tumors.
timeFrame: 12 weeks
measure: Subjects with basal subtype tumors who complete all intended neoadjuvant therapy and surgical therapy.
timeFrame: One year
measure: Subjects with classical subtype tumors who complete all intended neoadjuvant therapy and surgical therapy.
timeFrame: One year
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Medical Group
state: Arizona
city: Milwaukee
country: United States
facility: Froedtert & the Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Medical College of Wisconsin
name: Kathleen K Christians, MD
role: PRINCIPAL_INVESTIGATOR
References: