Study of NALIRIFOX in Advanced Unresectable Small Bowel Tumors

NCT06835387 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCRN GI23-617
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 7

Brief Summary

The study regimen will be administered on an outpatient basis and all medications are administered intravenously (IV). Subjects will receive treatment on Day 1 and Day 15 of each 28-day cycle consisting of the following: nanoliposomal irinotecan at 50 mg/m2, followed by oxaliplatin 60 mg/m2, followed by leucovorin at 400 mg/m2 30 minutes after completion of oxaliplatin, followed by 5-FU 2400 mg/m2 60 minutes after leucovorin completion. Subjects will receive up to 6 cycles of NALIRIFOX then based on response and per physician discretion, de-escalated maintenance treatment with NALIRIFOX minus oxaliplatin may continue. Subjects will continue de-escalated maintenance treatment until progression per RECIST 1.1, intolerable toxicity or physician/subject choice to discontinue.

Conditions

Small Bowel Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as the proportion of subjects with a confirmed complete or partial response to treatment according to RECIST 1.1, by local assessment.

  3 years

Secondary Outcomes (4)

• Overall Survival (OS)

  3 years

• Time to Progression (TTP)

  3 years

• Duration of Response (DOR)

  3 years

• Number of Participants with Adverse Events

  3 years

Study Arms (1)

NALIRIFOX and De-escalated maintenance

EXPERIMENTAL

Cycle 1 to Cycle 6: NALIRIFOX Subjects will receive treatment on Day 1 and Day 15 of each 28-day cycle consisting of the following: nanoliposomal irinotecan at 50 mg/m2, followed by oxaliplatin 60 mg/m2, followed by leucovorin at 400 mg/m2 30 minutes after completion of oxaliplatin, followed by 5-FU 2400 mg/m2 60 minutes after leucovorin completion. Patients will receive up to 6 cycles of NALIRIFOX. Cycle 7+: De-escalated Maintenance: Based on response to Cycles 1-6 and per physician discretion, de-escalated maintenance treatment with NALIRIFOX minus oxaliplatin may continue as de-escalated maintenance treatment until progression per RECIST 1.1, intolerable toxicity or physician/subject choice to discontinue.

Drug: Nanoliposomal irinotecan; Drug: Oxaliplatin; Drug: 5 fluorouracil; Drug: Leucovorin

Interventions

Oxaliplatin DRUG

Oxaliplatin 60 mg/m2 will be administered over 120 minutes (± 10 minutes) IV. Institutional standards may be used for all aspects of oxaliplatin administration including premedication administration.

Also known as: Eloxatin

NALIRIFOX and De-escalated maintenance

5 fluorouracil DRUG

5-FU will be administered as a continuous infusion over 46 hours. Subjects will go home with an infusion pump and return to clinic at the end of infusion for removal of the pump or, if possible, the pump may be removed at the subject's home (except on Cycle 1 Day 3).

Also known as: Tolak, Efudex, Fluoroplex

NALIRIFOX and De-escalated maintenance

Nanoliposomal irinotecan DRUG

Nanoliposomal Irinotecan 50 mg/m2 will be administered over 90 minutes (± 10 minutes) IV. All subjects must be pre-medicated prior to nanoliposomal irinotecan infusion with standard doses of dexamethasone and a 5-HT3 antagonist, or equivalent other anti-emetics (according to standard institutional practices).

Also known as: Onivyde

NALIRIFOX and De-escalated maintenance

Leucovorin DRUG

Leucovorin 400 mg/m2 will be administered over 30 minutes IV.

Also known as: Wellcovorin, folinic acid

NALIRIFOX and De-escalated maintenance

Eligibility Criteria

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

You may qualify if:

• Subject has been informed about the nature of the study, and has agreed to participate in the study, and signed the ICF prior to participation in any study-related activities. Also, as determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of ≤ 1 within 28 days prior to registration.
• Histological or cytologically confirmed small bowel adenocarcinoma per AJCC staging manual, 8th edition that has not been previously treated in the metastatic setting. Subjects with only localized disease or disease which will likely become resectable after chemotherapy (per investigator discretion) are NOT eligible. NOTE: Subjects may have received one cycle of FOLFOX without biologic therapy prior to screening for this trial.
• Mismatch repair proficient (MMRp) and/or microsatellite stable (MSS) disease per institutional standard of care testing. NOTE: Testing should be performed prior to receipt of one cycle of FOLFOX.
• Subject has one or more metastatic lesion(s) measurable by CT scan (or MRI, if the subject is allergic to CT contrast media) according to RECIST Version 1.1 criteria. Lesions in a prior radiation field must have progressed subsequent to radiotherapy to be considered measurable.
• Demonstrate adequate organ function as defined below. All screening labs to be obtained within 28 days prior to registration.
• Platelets (Plt) ≥ 100,000 cells/mm3
• Absolute Neutrophil Count (ANC) ≥ 1,500 cells/mm3; without the use of hemopoietic growth factors
• Hemoglobin (Hgb) ≥ 9 g/dL
• Calculated creatinine clearance ≥ 30 mL/min; Cockcroft-Gault formula for actual body weight should be used for calculation. For subjects with a body mass index (BMI) \> 30 kg/m2, adjusted body weight should be used instead
• Total bilirubin ≤ 1.5 × ULN
• Aspartate aminotransferase (AST) ≤ 2 × ULN; \< 5× with liver metastases
• Alanine aminotransferase (ALT) ≤ 2 × ULN; \< 5× with liver metastases
• Albumin ≥ 2.5 gm/dL

You may not qualify if:

• Adenocarcinoma originating in the ampulla or appendix. NOTE: Duodenal tumors that involve the ampulla but originate in the duodenum are eligible. In addition, ampullary cancers that demonstrate an intestinal phenotype based on H\&E and/or IHC (excluding biliary phenotype) are eligible.
• Neuroendocrine or any other histology different than adenocarcinoma.
• Prior treatment with irinotecan.
• Prior treatment of small bowel adenocarcinoma (SBA) in the metastatic setting with surgery, radiotherapy, chemotherapy or investigational therapy:
• Palliative radiotherapy is permitted but lesions in a prior radiation field must have progressed subsequent to radiotherapy to be considered measurable.
• Placement of biliary stent/tube is permitted.
• Palliative surgery (for example to treat obstruction)
• Clinically significant gastrointestinal disorder including hepatic disorders, bleeding, inflammation, occlusion, diarrhea \> Grade 1, malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, or bowel obstruction.
• Pregnant or breastfeeding. NOTE: breast milk cannot be stored for future use while the mother is being treated on study.
• Subjects with an active malignancy in the last 2 years. The following subjects may be eligible: Subjects with prior history of in-situ cancer or basal or squamous cell skin cancer. Subjects with a history of other malignancies but have been continuously disease free for at least 2 years without treatment prior to registration.
• Known hypersensitivity to any of the components of nanoliposomal irinotecan, other liposomal products, or any components of 5-FU, LV or oxaliplatin.
• Concurrent illnesses that would be a relative contraindication to trial participation such as active cardiac or liver disease, including:
• Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before registration
• High cardiovascular risk, including, but not limited to, recent coronary stenting or myocardial infarction in the past year prior to registration
• New York Heart Association (NYHA) Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure

Sponsors & Collaborators

• Tiago Biachi de Castria: lead
• Ipsen: collaborator
• H. Lee Moffitt Cancer Center and Research Institute: collaborator

Study Sites (7)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

RECRUITING

Parkview Research Center

Fort Wayne, Indiana, 46845, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Atlantic Health System

Morristown, New Jersey, 07960, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

RECRUITING

MeSH Terms

Interventions

irinotecan sucrosofate; Oxaliplatin; Fluorouracil; Leucovorin

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Tiago Biachi de Castria, MD, PhD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tiago Biachi de Castria, MD, PhD

CONTACT

8137452559; tiago.biachi@moffitt.org

LeaEtta Hyer

CONTACT

3176345842; lhyer@hoosiercancer.org

Study Design

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

Model Details: Subjects will receive treatment on Day 1 and Day 15 of each 28-day cycle consisting of the following: nanoliposomal irinotecan at 50 mg/m2, followed by oxaliplatin 60 mg/m2, followed by leucovorin at 400 mg/m2 30 minutes after completion of oxaliplatin, followed by 5-FU 2400 mg/m2 60 minutes after leucovorin completion. Patients will receive up to 6 cycles of NALIRIFOX then based on response and per physician discretion, de-escalated maintenance treatment with NALIRIFOX minus oxaliplatin may continue. Subjects will continue de-escalated maintenance treatment until progression per RECIST 1.1, intolerable toxicity or physician/subject choice to discontinue.

Study Record Dates

• First Submitted: February 14, 2025
• First Posted: February 19, 2025
• Study Start: June 30, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2028
• Last Updated: July 28, 2026

Record last verified: 2026-07

Locations

US (7)