Using NALIRIFOX to treat locally advanced pancreatic cancer

A Phase II Study of Liposomal Irinotecan (Nal-IRI) With 5 Fluorouracil, Leucovorin, and Oxaliplatin (NALIRIFOX) in Patients With Locally Advanced Pancreatic Cancer

This study is testing if the NALIRIFOX treatment can help people with locally advanced pancreatic cancer before surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: The First Affiliated Hospital with Nanjing Medical University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT06467565 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial evaluates the effectiveness of NALIRIFOX as induction therapy for patients with locally advanced pancreatic ductal adenocarcinoma. Participants will receive the NALIRIFOX regimen every two weeks in four-week cycles, with imaging assessments conducted after the first two cycles to monitor tumor response. If there is no disease progression, treatment will continue until surgical resection or other specified endpoints are met. Following 24 weeks of treatment, patients will transition to a maintenance regimen of capecitabine or S-1.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with histologically confirmed locally advanced pancreatic ductal adenocarcinoma who have not received prior chemotherapy or immunotherapy.

Not a fit: Patients with resectable pancreatic tumors or those who have previously undergone chemotherapy or targeted therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve surgical outcomes and overall survival for patients with locally advanced pancreatic cancer.

How similar studies have performed: While there have been studies on various treatments for pancreatic cancer, the specific use of NALIRIFOX in this context is relatively novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years old, ≤ 70 years old, male or female;
2. Understand the objectives and benefits and risks of the clinical trial, voluntarily participate in and sign the informed consent form;
3. ECOG score 0-1;
4. The subject had histopathologically or cytologically confirmed type of pancreatic ductal adenocarcinoma
5. Local progression according to the 2022 CSCO guidelines;
6. Initial subjects with locally advanced pancreatic cancer who have not undergone resection of pancreatic tumor (except open exploration or internal drainage surgery), chemotherapy, targeted, or immunotherapy.
7. At least one measurable pancreatic lesion per RECIST 1.1 criteria;
8. Expected survival time ≥ 3 months.
9. Heart, lung, liver, kidney and other major organ functions are basically normal.
10. Hematology tests should meet the following criteria (no blood transfusion, no use of blood products, granulocyte colony-stimulating factor, or other hematopoietic growth factors within 7 days prior to hematology):

    1. White blood cell count ≥ 3.0 × 109/L and neutrophil count ≥ 1.5 × 109/L.
    2. Platelet count ≥ 100 × 109/L.
    3. Hemoglobin ≥ 90 g/L.
    4. If component blood transfusions (red blood cells, platelets, etc.) are received at screening, reexamination of hematology must be performed at 1-week intervals before further screening can be considered.
11. Blood chemistry tests should meet the following criteria:

    1. Plasma total bilirubin ≤ 1.5 × upper limit of normal.
    2. ALT, AST, or ALP ≤ 2.5 × upper limit of normal;
    3. Creatinine clearance ≥30 mL/min calculated by the Cockcroft-Gault formula (Cockcroft-Gault formula: male Ccr = \[(140-age) × body weight (kg)\]/\[0.818 × Scr (μmol/L)\] or Ccr = (140-age) × body weight (kg)/72 × Scr (mg/dl), and female Ccr calculated as male × 0.85);
12. The subject had no symptoms of cardiac insufficiency (NYHA functional class ≤ II) at baseline and had no obvious abnormalities or abnormalities in electrocardiograms that were not clinically significant.
13. Good compliance, voluntary compliance with this clinical trial protocol and follow-up by the investigator during the study.
14. Subjects of childbearing potential voluntarily take highly effective contraceptive measures in the trial.
15. Females must be non-lactating.

Exclusion Criteria:

1. Known allergy or intolerance to the ingredients or excipients of this investigational product.
2. Any metastatic lesions.
3. Patients with unresolved acute or chronic infection
4. Other malignancies within 5 years (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix);
5. Active hepatitis.
6. Patients with portal hypertension or cavernous transformation of the portal vein; patients with gastrointestinal bleeding caused by tumor involving the digestive tract; patients with intra-abdominal fistula or abscess due to tumor involvement of digestive tract; the tumor encircles the celiac trunk or SMA and causes significant vascular wall involvement (worm-like changes);
7. Presence of third space effusion that cannot be controlled by drainage or other means (e.g., moderate-large pleural effusion, moderate-large pericardial effusion, ascites); a small amount of pleural effusion or ascites that is not clinically symptomatic and does not require clinical intervention should be strictly controlled before enrollment.
8. Mental illness or mental disorder, poor compliance, unable to cooperate with treatment
9. Patients with severe organic diseases or major organ failure, such as decompensated heart and lung failure, which lead to intolerance to chemotherapy.
10. Abnormal coagulation (INR \> 1.5, APTT \> 1.5 ULN), bleeding tendency (e.g., active ulcer lesions in the stomach, occult blood in stool (+ +), melena and/or hematemesis within 3 months, hemoptysis) or near the location of the lesion to major vessels.
11. Patients with Grade I or higher coronary heart disease, arrhythmia (including QTc prolongation \> 450 ms in males and \> 470 ms in females), taking arrhythmic drugs, or associated underlying heart disease and cardiac insufficiency.
12. Patients with renal insufficiency, previous renal disease, and positive urine protein (urine protein test 2 + or more, or 24-hour urineprotein quantitation \> 1.0 g).
13. Organ transplant recipients.
14. There are drug addicts and other adverse drug addicts, long-term alcoholics and AIDS and other infectious diseases.
15. Long-term use of corticosteroids or immunosuppressants.
16. Those who have received vaccines (including live and live attenuated vaccines) within 4 weeks prior to enrollment, such as measles, mumps, rubella, varicella, yellow fever, rabies, BCG, and typhoid (oral) vaccines, etc., or who plan to be vaccinated during study dosing; Allowing all types of COVID-19 vaccines.
17. Subjects with active hepatitis B or hepatitis C (HBV DNA ≥ 1 × 104 copies or ≥ 2000 IU/mL regardless of drug control; hepatitis C infection, HCV RNA ≥ 15 IU/mL); or HIV antibody positive (testing is not required if there is no clinical evidence of possible HIV infection); or syphilis antibody (TPPA) positive.
18. Breast feeding, known pregnancy, positive serum pregnancy test or unwillingness to use a reliable method of birth control, during therapy and for 6 months following the last dose of nal-IRI. Females of Childbearing Potential must either agree to use and be able to take effective contraceptive birth control measures (Pearl Index \< 1) or agree to use effective contraception during treatment and for at least 7 months after last application of program treatment. Males with female partners of reproductive potential should use condoms during treatment and for 4 months after the last dose. A female subject is considered to be of childbearing potential unless she is age ≥ 50 years and naturally amenorrhoeic for ≥ 2 years, or unless she is surgically sterile. Males must agree not to father a child (including not donating sperm) during the course of the trial and for at least 6 months after last administration of study drugs.
19. In the opinion of the investigator, the subject is unable to complete the entire trial process or other circumstances that are not suitable for participation in this trial.
20. Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1. Subjects are ineligible if:

    * they are unable to discontinue the use of strong inhibitors of CYP3A, CYP2C8 and UGT1A1 at least 1 week prior to first dosing
    * they are unable to discontinue the use of strong CYP3A and CYP2C8 inducers at least 2 weeks prior to first dosing.

Where this trial is running

Nanjing, Jiangsu

• The First Affiliated Hospital with Nanjing Medical University — Nanjing, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Rong K Jiang, MD

Conditions Pancreatic Ductal Adenocarcinoma