NALIRIFOX (Nal-IRI Plus 5-FU/LV Plus Oxaliplatin) as First-Line Treatment for Patients With Advanced Small Intestine and Appendiceal Cancers

NCT ID: NCT07060014

Last Updated: 2025-07-11

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-18
• Study Completion Date: 2026-12-31

Brief Summary

This study will evaluate the safety and efficacy of NALIRIFOX per NAPOLI-3 regimen as first-line chemotherapy for patients with advanced small intestine and appendiceal cancers. Female or male patients aged 18 years, or older, with histopathologically or cytologically confirmed advanced mucinous or non-mucinous appendix cancer or advanced small intestine cancer will be eligible for participation in the study.

Detailed Description

This study will evaluate the safety and efficacy of NALIRIFOX per NAPOLI-3 regimen as first-line chemotherapy for patients with advanced small intestine and appendiceal cancers. Female or male patients aged 18 years, or older, with histopathologically or cytologically confirmed advanced mucinous or non-mucinous appendix cancer or advanced small intestine cancer will be eligible for participation in the study. Approximately, 22 patients will be enrolled in the study. The study drugs will be administered per the regimen defined in the NAPOLI-3 clinical trial, NCT04083235. Patients will be treated with NALIRIFOX (liposomal irinotecan 50 mg/m2 + 5-FU 2400 mg/m2 + LV 400 mg/m2 + oxaliplatin 60 mg/m2) every 2 weeks for 12 months.

Conditions

Advanced Small Intestine Cancer; Appendiceal Cancers

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

nal-IRI plus 5-FU/LV plus NALIRIFOX

Patients in this arm will receive NALIRIFOX

Group Type: EXPERIMENTAL

Patients will be treated with NALIRIFOX (liposomal irinotecan 50 mg/m2 + 5-FU 2400 mg/m2 + LV 400 mg/m2 + oxaliplatin 60 mg/m2, IV) every 2 weeks for 12 months

Intervention Type: DRUG

The study drugs will be administered per the regimen defined in the NAPOLI-3 clinical trial. Patients will be treated with NALIRIFOX (liposomal irinotecan 50 mg/m2 + 5-FU 2400 mg/m2 + LV 400 mg/m2 + oxaliplatin 60 mg/m2, IV) every 2 weeks for 12 months.

Historical Control Arm

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Patients will be treated with NALIRIFOX (liposomal irinotecan 50 mg/m2 + 5-FU 2400 mg/m2 + LV 400 mg/m2 + oxaliplatin 60 mg/m2, IV) every 2 weeks for 12 months

The study drugs will be administered per the regimen defined in the NAPOLI-3 clinical trial. Patients will be treated with NALIRIFOX (liposomal irinotecan 50 mg/m2 + 5-FU 2400 mg/m2 + LV 400 mg/m2 + oxaliplatin 60 mg/m2, IV) every 2 weeks for 12 months.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male or female ≥18 years of age.

2. Histopathologically or cytologically confirmed advanced mucinous or non-mucinous appendix cancer or advanced small intestine cancer.

3. Measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

4. Eastern Cooperative Oncology Group performance status of 0 or 1.

5. Life expectancy ≥6 months.

6. Patients of childbearing potential must agree to use an adequate method of contraception during the study and for 30 days after the last dose of study treatment.

Exclusion Criteria

• 1. Hematology laboratory values of:

1. Absolute neutrophil count ≤1500 cells/mm3

2. Platelets ≤100,000 cells/mm3

3. Hemoglobin ≤9 g/dL

4. White blood count ≤3000 cells/mm3. 2. Hepatic laboratory values of aspartate transaminase or alanine aminotransferase:

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1. >5 × upper limits of normal (ULN) if the documented history of hepatic metastases; or

2. >2.5 × ULN if no liver metastases are present. 3. Total bilirubin >1.5 × ULN or >1.5 mg/dL. 4. Prothrombin time (PT) or international normalized ratio (INR) >1.5 × ULN. Note: Patients receiving therapeutic doses of anticoagulant therapy may be considered eligible if PT and INR are within the acceptable institutional therapeutic limits.

5. Serum creatinine or serum urea >1.5 × ULN. 6. Estimated glomerular filtration rate <50 mL/min. 7. Positive pregnancy test, pregnancy, or breastfeeding (female patients only). 8. Any other clinically significant laboratory abnormality that would compromise patient safety or the outcome of the study.

9. Any clinically significant and/or uncontrolled cardiac-related abnormality that would compromise patient safety or the outcome of the study including, but not limited to:

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1. Arrhythmia

2. Bradycardia

3. Tachycardia

4. Symptomatic valvular disease

5. Symptomatic congestive heart failure is classified by the New York Heart Association as Class III or IV

6. Unstable angina pectoris. 10. Myocardial infarction within the past 6 months. 11. Active bleeding diathesis. 12. Current complaints of persistent constipation or history of chronic constipation, bowel obstruction, or fecaloma within the past 6 months.

13. Receiving chronic treatment with corticosteroids ≥5 mg of prednisone per day (or equivalent) or another immunosuppressive agent (s) 14. Known history and/or uncontrolled hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV)-1 or HIV-2.

15. History of galactose intolerance, deficiency of Lapp lactase, or glucose-galactose malabsorption.

16. History of malignancy or active treatment for malignancy (i.e., radiation or chemotherapy, including monoclonal antibodies) within 5 years. Note: Patients with squamous or basal cell carcinomas of the skin, carcinomas in situ of the cervix or uterus, ductal breast cancer in situ, resected low-grade prostate cancer, or other malignancies that in the opinion of the investigator are considered cured may participate.

17. Receipt of live, attenuated vaccine (e.g., intranasal influenza, measles, mumps, rubella, varicella) or close contact with someone who has received a live, attenuated vaccine within the past 1 month. Note: Influenza vaccine will be allowed if administered >21 days.

18. Receipt of any investigational agent or study treatment within the past 30 days.

19. Receipt of any protein or antibody-based therapeutic agents (e.g., growth hormones or monoclonal antibodies) within the past 3 months.

20. Allergies reaction to irinotecan or liposomal irinotecan.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Methodist Hospital Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Maen Abdelrahim, MD, PhD, Pharm.B

Chief Gastrointestinal Medical Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Abdullah Esmail, MD

Role: STUDY_DIRECTOR

Houston Methodist Nael Cancer Center

Locations

Houston Methodist Hospital

Houston, Texas, United States

Countries

United States

Central Contacts

Maen Abdelrahim, MD,PhD

Role: CONTACT

mabdelrahim@houstonmethodist.org

713-441-1240

Abdullah Esmail, MD

Role: CONTACT

AEsmail@houstonmethodist.org

Facility Contacts

Jennifer Garrett, RN

Role: primary

jmgarrett@houstonmethodist.org

346-238-4516

Abdullah Esmail, MD

Role: backup

aesmail@houstonmethodist.org

Other Identifiers

PRO00038285

Identifier Type: -

Identifier Source: org_study_id