FOLFIRINOX + Elraglusib + Losartan In Pancreatic Cancer

NCT05077800 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 21-350
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to find out if an experimental drug will prevent metastatic pancreatic adenocarcinoma from becoming resistant to standard treatment for the disease. The names of the study drugs involved in this study are:

• 9-ING-41
• Losartan
• Ferumoxytol
• FOLFIRINOX (made up of 4 different drugs):
• 5-Fluorouracil (5-FU)
• Oxaliplatin
• Irinotecan
• Leucovorin

Conditions

Pancreatic Adenocarcinoma; Pancreatic Adenocarcinoma Metastatic

Keywords

Pancreatic Adenocarcinoma; Pancreatic Adenocarcinoma Metastatic

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  Defined from the date of study entry to the earliest date of progressive disease while receiving complete therapy with FOLFIRINOX-based therapy or death due to any cause. PFS will be censored at the date of last follow-up for patients alive without documented progression. PFS curves will be estimated by the Kaplan-Meier method and compared to historical controls treated with FOLFIRINOX alone using the one-sample log-rank test.

  Date of study entry to the earliest date of progressive disease up to 30 months

Secondary Outcomes (3)

• Overall survival (OS)

  Up to 30 months

• Median time of maintenance therapy (mMT):

  Up to 30 months

• Objective Response Rate

  Up to 30 months

Study Arms (5)

Safety Run-In: FOLFIRINOX + Elraglusib + Losartan

EXPERIMENTAL

The study will begin with a Safety Run-In phase to establish the side effects from the study treatment to its safety before beginning the main part of the study, six (6) participants will receive 1-2 cycles (each study cycle is 14 days +/- 3 days) of: * FOLFIRINOX * 5Fluorouracil portion of FOLFIRINOX on Days 1-3 of each study cycle * Irinotecan portion of FOLFIRINOX on Day 1 of each study cycle * Oxaliplatin portion of FOLFIRINOX on Day 1 of each study cycle * Leucovorin portion of FOLFIRINOX on Day 1 of each study cycle The FOLFIRINOX treatment regimen will be given every 14 days +/- 3 days at physician discretion. * Elraglusib on days on days 1, 3, 8, and 11 of every 14-day cycle * Losartan daily of every 14-day cycle.

Drug: FOLFIRNINOX; Drug: Losartan; Drug: 9-ING-41

FOLFIRNINOX

EXPERIMENTAL

The study will be conducted in three parts depending on participant disease progression: Complete Therapy, Maintenance Therapy and Complete Therapy Round 2. For initial complete therapy, participants will receive FOLFIRINOX as follows (each study cycle is 14 days +/- 3 days, FOLFIRINOX can be given +/- 3 days): * 5Fluorouracil portion of FOLFIRINOX on Days 1-3 of each study cycle up to 12 cycles (24 weeks) * Irinotecan portion of FOLFIRINOX on Day 1 of each study cycle up to 12 cycles (24 weeks) * Oxaliplatin portion of FOLFIRINOX on Day 1 of each study cycle up to 12 cycles (24 weeks) * Leucovorin portion of FOLFIRINOX on Day 1 of each study cycle up to 12 cycles (24 weeks) For Maintenance therapy, participants will receive FOLFIRINOX as follows: * 5Fluorouracil portion of FOLFIRINOX on Days 1-3 of each 14 day study cycle until disease progression For Complete Therapy Round 2, participants will repeat initial complete therapy of FOLFIRINOX until further disease progression

Drug: FOLFIRNINOX

FOLFIRINOX + Losartan

EXPERIMENTAL

The study will be conducted in three parts depending on participant disease progression: Complete Therapy, Maintenance Therapy and Complete Therapy Round 2. For initial complete therapy (each study cycle is 14 days +/- 3 days): * FOLFIRINOX (+/- 3 days) * 5Fluorouracil portion of FOLFIRINOX on Days 1-3 of each study cycle up to 12 cycles (24 weeks) * Irinotecan portion of FOLFIRINOX on Day 1 of each study cycle up to 12 cycles (24 weeks) * Oxaliplatin portion of FOLFIRINOX on Day 1 of each study cycle up to 12 cycles (24 weeks) * Leucovorin portion of FOLFIRINOX on Day 1 of each study cycle up to 12 cycles (24 weeks) * Losartan daily up to 12 cycles (24 weeks) For Maintenance therapy: * 5Fluorouracil portion of FOLFIRINOX on Days 1-3 of each 14 day study cycle until disease progression * Losartan daily until disease progression For Complete Therapy Round 2, participants will repeat initial complete therapy of FOLFIRINOX + Losartan until further disease progression

Drug: FOLFIRNINOX; Drug: Losartan

FOLFIRINOX + Elraglusib

EXPERIMENTAL

The study conducted in 3 parts depending on disease progression: Complete Therapy, Maintenance Therapy and Complete Therapy Round 2 For initial complete therapy (each study cycle is 14 days +/- 3 days): * FOLFIRINOX (+/- 3 days) * 5Fluorouracil portion of FOLFIRINOX on Days 1-3 of each study cycle up to 12 cycles (24 weeks) * Irinotecan portion of FOLFIRINOX on Day 1 of each study cycle up to 12 cycles (24 weeks) * Oxaliplatin portion of FOLFIRINOX on Day 1 of each study cycle up to 12 cycles (24 weeks) * Leucovorin portion of FOLFIRINOX on Day 1 of each study cycle up to 12 cycles (24 weeks) * Elraglusib on days 1, 3, 8, and 11 of every study cycle up to 12 cycles (24 weeks) For Maintenance therapy: * 5Fluorouracil portion of FOLFIRINOX on Days 1-3 of each study cycle until disease progression * Elraglusib on days 1, 3, 8, and 11 of every study cycle until disease progression For Complete Therapy Round 2, repeat of initial complete therapy until further disease progression

Drug: FOLFIRNINOX; Drug: 9-ING-41

FOLFIRINOX + Elraglusib + Losartan

EXPERIMENTAL

The study conducted in 3 parts depending on disease progression: Complete Therapy, Maintenance Therapy and Complete Therapy Round 2. For initial complete therapy (each study cycle is 14 days +/- 3 days): * FOLFIRINOX (+/- 3 days) * 5Fluorouracil portion of FOLFIRINOX on Days 1-3 of each study cycle * Irinotecan portion of FOLFIRINOX on Day 1 of each study cycle * Oxaliplatin portion of FOLFIRINOX on Day 1 of each study cycle * Leucovorin portion of FOLFIRINOX on Day 1 of each study cycle * Elraglusib on days 1, 3, 8, and 11 of every 14-day cycle * Losartan daily For Maintenance therapy: * 5Fluorouracil portion of FOLFIRINOX on Days 1-3 of each 14 day study cycle until disease progression * Elraglusib on days 1, 3, 8, and 11 of every 14-day cycle until disease progression * Losartan daily until disease progression For Complete Therapy Round 2, participants will repeat initial complete therapy of FOLFIRINOX + Elraglusib + Losartan until further disease progression

Drug: FOLFIRNINOX; Drug: Losartan; Drug: 9-ING-41

Interventions

FOLFIRNINOX DRUG

Combination of 4 different drugs (5-Fluorouracil (5-FU), Oxaliplatin, Irinotecan and Leucovorin) administered by intravenous infusion

FOLFIRINOX + Elraglusib; FOLFIRINOX + Elraglusib + Losartan; FOLFIRINOX + Losartan; FOLFIRNINOX; Safety Run-In: FOLFIRINOX + Elraglusib + Losartan

Losartan DRUG

Taken Orally

Also known as: Cozaar

FOLFIRINOX + Elraglusib + Losartan; FOLFIRINOX + Losartan; Safety Run-In: FOLFIRINOX + Elraglusib + Losartan

9-ING-41 DRUG

Administered by intravenous infusion

Also known as: Elraglusib

FOLFIRINOX + Elraglusib; FOLFIRINOX + Elraglusib + Losartan; Safety Run-In: FOLFIRINOX + Elraglusib + Losartan

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed metastatic pancreatic adenocarcinoma without prior therapy for pancreatic adenocarcinoma.
• Participants must have measurable disease as defined by RECIST 1.1
• Age ≥18 years.
• ECOG performance status ≤1 (Karnofsky ≥ 70%, see Appendix A).
• Participants must have adequate organ and marrow function as defined below:
• Absolute neutrophil count (ANC) ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN) if no biliary stenting has been done OR 2.0 x ULN if patient is status post biliary stenting or two downward trending values.
• AST(SGOT)/ALT(SGPT) \< 5 x institutional ULN.
• Creatinine ≤ 1.5 mg/dL OR .
• Creatinine clearance ≥ 30 mL/min (as estimated by Cockcroft Gault Equation)
• (140 - age \[yrs\]) (body wt \[kg\]) Creatinine clearance for males = ------------ (72) (serum creatinine \[mg/dL\])
• Creatinine clearance for females = 0.85 x male value
• Prior treatment with angiotensin receptor blocker (ARB) for hypertension is allowed. If the patient is randomized to a non-losartan containing treatment arm, the patient must be changed to an antihypertensive medication that is not in the class of angiotensin receptor blocker (ARB).
• Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy within 6 months are eligible for this trial.

You may not qualify if:

• Any prior chemotherapy, radiation therapy, immunotherapy, biologic ('targeted') therapy or investigational therapy for pancreas adenocarcinoma. No prior adjuvant or neoadjuvant therapy for localized pancreatic adenocarcinoma is allowed.
• Patients with deleterious or suspected deleterious germline or somatic BRCA-mutated pancreatic cancer.
• Patients with TRK (tropomyosin receptor kinase) fusion-positive cancers.
• Patients with deficient mismatch/microsatellite unstable or high tumor mutation burden cancers.
• Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment, without complete recovery
• Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
• Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia.
• The investigator(s) must state a medical or scientific reason if participants who have brain metastases will be excluded from the study.
• History of allergic reactions attributed to compounds of similar chemical composition to 9-ING-41, losartan, 5-fluorouracil, irinotecan and oxaliplatin not amenable to institutional chemotherapy desensitization protocol. Prior topical fluoropyrimidine use is allowed.
• Patients with cardiac ventricular arrhythmias requiring antiarrhythmic therapy, or atrioventricular heart block (due to 5FU administration)
• Known, existing uncontrolled coagulopathy. Concomitant treatment with full dose warfarin (coumadin) is NOT allowed. Patients may receive low molecular weight heparin (LMWH) (such as enoxaparin and dalteparin) and direct oral anticoagulant (DOAC) for management of deep venous thrombosis (DVT).
• Patients taking strong inhibitors of CYP2C19, CYP3A4, and CYP1A2 or strong inducers of CYP3A4 should only be entered into the study protocol if deemed by the investigator to be in their best interest and with study medical coordinator agreement
• Concomitant use of cimetidine, as it can decrease clearance of 5FU. Another H2-blocker or proton pump inhibitor may be substituted before study entry.
• Participants with uncontrolled intercurrent illness.
• Participants with uncontrolled seizures, central nervous system disorders or psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• Colin D. Weekes, M.D., PhD: lead
• Actuate Therapeutics Inc.: collaborator
• Lustgarten Foundation: collaborator

Study Sites (4)

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Massachusetts General Hospital

Charlestown, Massachusetts, 02129, United States

Location

University of Washington School of Medicine

Seattle, Washington, 98109, United States

Location

MeSH Terms

Interventions

Losartan; 3-(5-fluorobenzofuran-3-yl)-4-(5-methyl-5H-(1,3)dioxolo(4,5-f)indol-7-yl)-pyrrole-2,5-dione

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Study Officials

• Colin D Weekes, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 1, 2021
• First Posted: October 14, 2021
• Study Start: March 21, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (4)