Pancreatic Adenocarcinoma Signature Stratification for Treatment

NCT04469556 | Completed Phase 2 DMC

• 2 other identifiers: PASS-01CAPCR ID: 20-5105
• Study Type: interventional
• Target: 150
• Locations: 2 countries
• Sites: 6

Brief Summary

This is a randomized multicentre phase II trial with a large translational component. The trial will evaluate the two standard chemotherapy regimens: modified folfirinox (mFFX) and gemcitabine/nab-paclitaxel (GA), in patients with untreated metastatic pancreatic ductal adenocarcinoma. Integrated into this phase II trial are a number of laboratory components including molecular profiling, patient derived organoid establishment, and drug testing sensitivity and other biomarkers.

Conditions

Pancreatic Cancer Metastatic; Pancreatic Ductal Adenocarcinoma; Advanced Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Progression free survival(PFS) in mFFX and GA arms pancreatic ductal adenocarcinoma (PDAC) in a randomized phase II trial.

  Time from the date of randomization to progression based on the radiology assessment of response using RECIST v1.1, or death, whichever is earlier

  2-4 years

Secondary Outcomes (8)

• ORR by RECIST 1.1 and duration of response in patients receiving mFFX or GA

  2-4 years

• Overall survival (OS) associated with mFFX or GA profiles, signatures and pharmacotyping

  2-4 years

• GATA6 as a biomarker of response to mFFX or GA

  2-4 years

• • Concordance between organoid transcriptomic profiles (RNAseq) and patient transcriptomic profiles (descriptive statistics)

  2-4 years

• • Concordance between chemotherapy sensitivity signature predictions and response to first line treatment (descriptive statistics).

  2-4 years

Study Arms (2)

Modified Folfirinox

ACTIVE COMPARATOR

Modified FOLFIRINOX (Folinic acid/Leucovorin, 5-Fluouracil, Irinotecan, Oxaliplatin) administered intravenously. Given that both regimens are standard of care, study treatment will be administered as per standard of care at each institution including a maintenance therapy approach which is encouraged in both arms. Dose modifications, anti-emetics, supportive medications, and use of growth factors should follow institutional guidelines.

Drug: Folfirinox

Gemcitabine/nab-Paclitaxel

ACTIVE COMPARATOR

Gemcitabine/nab-Paclitaxel administered intravenously. Given that both regimens are standard of care, study treatment will be administered as per standard of care at each institution including a maintenance therapy approach which is encouraged in both arms. Dose modifications, anti-emetics, supportive medications, and use of growth factors should follow institutional guidelines.

Drug: Gemcitabine/nab-paclitaxel

Interventions

Gemcitabine/nab-paclitaxel DRUG

Chemotherapy

Gemcitabine/nab-Paclitaxel

Folfirinox DRUG

Chemotherapy

Also known as: Folinic Acid/Leucovorin, 5-Fluouracil, Irinotecan, Oxaliplatin

Modified Folfirinox

Eligibility Criteria

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

You may qualify if:

• Patients must have a histological or radiological diagnosis of untreated metastatic PDAC at screening with histology subsequently confirmed prior to randomization.
• Eligible histologic variants include adenocarcinoma or variants to include mucinous adenocarcinoma or adenosquamous carcinoma.
• Patients with a history of prior or concurrent second primary malignancy whose natural history or treatment does not have the potential to interfere with the safety or primary endpoint efficacy assessment of the pancreas cancer should generally be eligible for enrollment in clinical trials.
• Age ≥18 years.
• Patient must have a tumor lesion that is amenable to a core needle biopsy.
• Patients must be suitable for treatment with either mFFX and GA without contraindications to either regimen.
• Eastern Cooperative Group (ECOG) performance status 0-1. (Karnofsky ≥70%).
• Life expectancy of greater than 90 days, as judged by the investigator
• Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test and must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
• Within 14 days of the proposed randomization date, patients must have normal organ and marrow function

You may not qualify if:

• Patients who have received prior systemic treatment for PDAC, including treatment in the neoadjuvant or adjuvant setting. Prior surgery or palliative radiation is permitted.
• Patients with histology other than pancreatic ductal adenocarcinoma. Those with adenosquamous are allowed. Acinar tumors and colloid are excluded.
• Patients with one or more contraindications to tumor biopsy according to local institution's standard biopsy procedures.
• Patients with known brain metastases are excluded from participation in this clinical study.
• Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, inability to stop anticoagulation medication for a biopsy, or psychiatric illness/social situations that would limit compliance with study requirements.
• Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
• Patients with a known germline mutation in BRCA, PALB2 or other homologous Recombination Repair Deficiency (HRD) genes.
• Patients who are pregnant or breastfeeding.
• Use (including 'recreational use') of any illicit drugs or other substance abuse (including alcohol) that could potentially interfere with adherence to study procedures or requirements. \*Use of any illicit drugs or other substance abuse (including alcohol) are not screened in Canada using Toxicity testing. -

Sponsors & Collaborators

• Stand Up To Cancer: collaborator
• University Health Network, Toronto: lead
• Johns Hopkins University: collaborator
• Cold Spring Harbor Laboratory: collaborator
• Ontario Institute for Cancer Research: collaborator
• Dana-Farber Cancer Institute: collaborator
• Memorial Sloan Kettering Cancer Center: collaborator

Study Sites (6)

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Northwell Health

New Hyde Park, New York, 11042, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

BC Cancer Agency Vancouver

Vancouver, British Columbia, V5Z 1L8, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2N9, Canada

Location

MeSH Terms

Interventions

folfirinox; Irinotecan; Oxaliplatin

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals

Study Officials

• Elizabeth Jaffee, MD

  Johns Hopkins University

  STUDY CHAIR

• Jennifer J Knox, MD

  University Health Network, Toronto

  STUDY CHAIR

Study Design

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

Model Details: Approximately 150 patients will be randomized in a 1:1 ratio to receive one of the two standard of care regimens in patients with confirmed metastatic PDAC

Study Record Dates

• First Submitted: June 26, 2020
• First Posted: July 14, 2020
• Study Start: October 14, 2020
• Primary Completion: March 5, 2025
• Study Completion: March 5, 2025
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); CA (2)