NeoOPTIMIZE: Early Switching of mFOLFIRINOX or Gemcitabine/Nab-Paclitaxel Before Surgery for the Treatment of Resectable, Borderline Resectable, or Locally-Advanced Unresectable Pancreatic Cancer

NCT04539808 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 2 other identifiers: STUDY00021614NCI-2020-06277
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial evaluates whether early switching from modified fluorouracil/irinotecan/leucovorin/oxaliplatin (mFOLFIRINOX) chemotherapy regimen to a combination of gemcitabine and nab-paclitaxel (GA) before surgery is effective in treating patients with pancreatic cancer that can be surgically removed (resectable or borderline resectable), or that has spread to nearby tissue or lymph nodes and cannot be removed by surgery (locally-advanced unresectable). Chemotherapy drugs, such as fluorouracil, irinotecan, leucovorin, oxaliplatin, gemcitabine, and nab-paclitaxel work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. The study will also evaluate the drug losartan in combination with mFOLFIRINOX or GA.

Conditions

Stage I Pancreatic Cancer American Joint Committee on Cancer v8; Stage III Pancreatic Cancer American Joint Committee on Cancer v8; Pancreatic Adenocarcinoma; Stage 0 Pancreatic Cancer American Joint Committee on Cancer v8; Stage IV Pancreatic Cancer American Joint Committee on Cancer v8

Outcome Measures

Primary Outcomes (1)

• Proportion of Resectable or BRPC Participants With R0 Resection

  Using the surgery analysis set, the proportion of resectable or BRPC participants with R0 resection will be estimated with exact 95% CI.

  Up to time of surgery

Secondary Outcomes (9)

• Progression-free Survival (PFS) NeoOPTIMIZE

  From the start of neoadjuvant therapy (day 1) to the time of tumor progression, or death due to any cause, assessed up to 24 months

• PFSNeoOPTIMIZE + Pre-operative (Preop)-RT

  From the start of neoadjuvant therapy (day 1) to the time of tumor progression, or death due to any cause, assessed up to 24 months

• Disease-free Survival (DFS) NeoOPTIMIZE

  From the date of surgery to the time of tumor progression, or death due to any cause, assessed up to 24 months

• DFSNeoOPTIMIZE + Preop-RT

  From the date of surgery to the time of tumor progression, or death due to any cause, assessed up to 24 months

• Overall Survival (OS) NeoOPTIMIZE

  From the start of neoadjuvant therapy (day 1) to death due to disease, assessed up to 24 months

Other Outcomes (10)

• CA19-9 Serum Levels (U/ml)

  Baseline up to 24 months

• Proportion of LAPC Participants With R0 Resection

  From the start of neoadjuvant therapy (day 1) to time of surgery

• PFSNeoOPTMIZE for LAPC Cohort

  From the start of neoadjuvant therapy (day 1) to time of tumor progression, or death due to any cause (up to 24 months from start of study treatment)

Study Arms (1)

Treatment (mFOLFIRINOX, chemotherapy)

EXPERIMENTAL

mFOLFIRINOX REGIMEN: Oxaliplatin intravenously (IV) over 2 hrs, leucovorin calcium IV over 2 hrs, and irinotecan hydrochloride IV over 90 minutes on day 1. Also receive fluorouracil IV over 46 hrs starting on day 1. Repeats every 14 days for up to 4 cycles. Those with response and no disease progression may receive an additional 2 months. GA REGIMEN: Those with disease progression or toxicity to mFOLFIRINOX switch to GA regimen comprising gemcitabine hydrochloride IV over 30-60 mins and nab-paclitaxel IV over 30-40 mins on days 1, 8, and 15. Repeats every 28 days for 2 cycles. LOSARTAN: Cycle 1 day 1, start losartan potassium orally once daily until end of RT. RT/SURGERY: Short-course RT for 10 fractions over 5 days weekly or long-course RT with 15-25 fractions over 5 days weekly along with oral capecitabine twice daily on Monday-Friday or fluorouracil IV over 5-7 days weekly until completion of RT. Patients then undergo surgery 1-4 weeks following RT

Drug: Capecitabine; Drug: Fluorouracil; Drug: Irinotecan Hydrochloride; Drug: Leucovorin Calcium; Drug: Losartan Potassium; Drug: Oxaliplatin; Radiation: Radiation Therapy; Procedure: Resection; Procedure: Diagnostic Imaging; Procedure: Biospecimen Collection; Drug: Gemcitabine; Drug: Nab paclitaxel

Interventions

Leucovorin Calcium DRUG

Given IV

Also known as: Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calfolex, Calinat, Cehafolin, Citofolin, Citrec, Citrovorum Factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Factor, Citrovorum, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Imo, Lederfolat, Lederfolin, Leucosar, leucovorin, Rescufolin, Rescuvolin, Tonofolin, Wellcovorin

Treatment (mFOLFIRINOX, chemotherapy)

Losartan Potassium DRUG

Given PO

Also known as: Cozaar, losartan

Treatment (mFOLFIRINOX, chemotherapy)

Oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669

Treatment (mFOLFIRINOX, chemotherapy)

Radiation Therapy RADIATION

Undergo short-course or long-course RT

Also known as: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (mFOLFIRINOX, chemotherapy)

Diagnostic Imaging PROCEDURE

Undergo diagnostic imaging

Also known as: Medical Imaging

Treatment (mFOLFIRINOX, chemotherapy)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (mFOLFIRINOX, chemotherapy)

Gemcitabine DRUG

Given IV

Also known as: Gemcitabine hydrochloride, Gemzar

Treatment (mFOLFIRINOX, chemotherapy)

Nab paclitaxel DRUG

Given IV

Also known as: Albumin-bound paclitaxel, Protein-bound paclitaxel, Abraxane

Treatment (mFOLFIRINOX, chemotherapy)

Irinotecan Hydrochloride DRUG

Given IV

Also known as: Campto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, Irinomedac, Irinotecan Hydrochloride Trihydrate, Irinotecan Monohydrochloride Trihydrate, U-101440E

Treatment (mFOLFIRINOX, chemotherapy)

Capecitabine DRUG

Given PO

Also known as: Ro 09-1978/000, Xeloda

Treatment (mFOLFIRINOX, chemotherapy)

Fluorouracil DRUG

Given IV

Also known as: 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-Fu, 5FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

Treatment (mFOLFIRINOX, chemotherapy)

Resection PROCEDURE

Undergo surgical resection

Also known as: Surgical Resection

Treatment (mFOLFIRINOX, chemotherapy)

Eligibility Criteria

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

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Cytologic or histologic proof pancreatic ductal carcinoma is required prior to study entry
• If a biopsy (e.g., endoscopic ultrasound \[EUS\]-guided fine needle aspiration \[FNA\]) is planned per standard of care, the participant may be asked to consent to the additional collection of tumor tissue for research
• No evidence of metastatic disease as determined by chest computed tomography (CT) scan, abdomen/pelvis computed tomography (CT) scan (or magnetic resonance imaging \[MRI\] with gadolinium and/or manganese) within the 45-day window of study entry or prior to the one cycle of standard of care (SOC) administered before study entry, which is consistent with the standard of care
• Note: On a case by case basis, for participants who enroll on trial after having received up to 1 month of standard of care chemotherapy per Investigator discretion, baseline radiographic imaging performed per institutional guidelines prior to SOC chemotherapy treatment may be used per investigator discretion to fulfill baseline radiographic imaging criteria even if performed \> 45 days prior to official study entry.
• Diagnostic staging laparoscopy is not required for study eligibility
• If staging laparoscopy is planned per standard of care, the participant may be asked to consent to the collection of tumor tissue for research
• At time of screening, per National Comprehensive Cancer Network (NCCN) criteria, must have either:
• Resectable pancreatic ductal adenocarcinoma (PDAC), defined as no arterial tumor contact (celiac axis \[CA\], superior mesenteric artery \[SMA\], or common hepatic artery \[CHA\]), or
• Node positive disease as defined by CT, MRI, or EUS imaging, or
• Borderline resectable PDAC, defined as:
• For tumors of the head or uncinate process:
• Solid tumor contact with the superior mesenteric vein (SMV) or portal vein of \> 180 degrees with contour irregularity of the vein or thrombosis of the vein, but with suitable vessel proximal and distal to the site of involvement, allowing for safe and complete resection and vein reconstruction

You may not qualify if:

• History of previous chemotherapy (other than no more than one cycle of standard systemic chemotherapy), targeted/biologic therapy, or radiation therapy for the treatment of their PDAC
• Evidence of metastasis to distant organs (liver, peritoneum, lung, others)
• Any other active malignancy or prior history of malignancy with less than a 90% cure rate in the judgement of the investigators
• Medical co-morbidities that are deemed to make risk of surgery unacceptably high as determined by institutional standards
• Personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest. Patients with cardiovascular conditions that are well-controlled in the clinical judgement of the treating oncologist are eligible to participate
• Recent major surgery (excluding laparoscopy) within 4 weeks prior to starting study treatment. Minor surgery within 2 weeks of starting study treatment. Patients must be recovered from effects of surgery
• Concomitant use of other anti-cancer therapy (chemotherapy, immunotherapy, hormonal therapy \[hormone replacement therapy is acceptable\]), not otherwise allowed in this study. Note: participation in other trials for supportive cancer care (e.g., cancer-related cachexia) interventions is permitted per PI discretion.
• Participants with a history of hypersensitivity reactions to study agents or their excipients. In cases of losartan hypersensitivity, losartan will be omitted and patient may still be eligible to participate
• Participant is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 30 days after the last dose of trial therapy
• Psychiatric illness/social situations, or any condition that, in the opinion of the investigator, would: interfere with evaluation of study treatment or interpretation of participant safety or study results, or substantially increase risk of incurring adverse events (AEs), or compromise the ability of the patient to give written informed consent
• Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Oregon Health and Science University: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Interventions

Capecitabine; Fluorouracil; dehydroftorafur; Irinotecan; Leucovorin; Losartan; Oxaliplatin; Radiotherapy; Radiation; X-Rays; Specimen Handling; Gemcitabine; Taxes; Albumin-Bound Paclitaxel

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Tetrazoles; Coordination Complexes; Therapeutics; Physical Phenomena; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Radiation, Ionizing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Economics; Health Care Economics and Organizations; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr. Charles Lopez, Professor
• Organization: Oregon Health & Science University

GIResearch@ohsu.edu

503-494-1080

Study Officials

• Charles D Lopez

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 31, 2020
• First Posted: September 7, 2020
• Study Start: May 27, 2021
• Primary Completion: December 8, 2024
• Study Completion (Estimated): January 5, 2027
• Last Updated: January 14, 2026
• Results First Posted: January 14, 2026

Record last verified: 2025-12

Locations

US (1)