NALIRIFOX for Appendiceal and Small Intestine Cancers

Overseen By Abdullah Esmail, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: The Methodist Hospital Research Institute

Must not be taking: Corticosteroids, Immunosuppressants, others

Disqualifiers: Cardiac abnormalities, Constipation, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called NALIRIFOX, a combination chemotherapy regimen, to determine its safety and effectiveness for individuals with advanced cancers of the appendix or small intestine. The goal is to establish it as a first-line treatment for these specific cancers. Individuals diagnosed with advanced appendix or small intestine cancer, whose symptoms impact daily life, might be suitable candidates. Participants will receive NALIRIFOX, and their progress will be compared to a group of past patients who did not receive this treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on corticosteroids or immunosuppressive agents, you may need to stop or adjust them, as the trial excludes those on certain doses of these medications.

Is there any evidence suggesting that NALIRIFOX is likely to be safe for humans?

Research has shown that NALIRIFOX, a combination of chemotherapy drugs including nal-IRI, 5-FU/LV, and oxaliplatin, has generally been safe in past studies. For example, one study found that when nal-IRI was combined with another drug, S-1, patients with advanced pancreatic cancer tolerated it well. Most side effects, such as nausea and tiredness, were manageable.

Another study examined a similar treatment using nal-IRI with 5-FU/LV and found that patients handled the drug fairly well. Common side effects were mild to moderate, including diarrhea and low blood counts. While these side effects are typical with chemotherapy, proper care generally made them manageable.

Since this trial is in an early phase, it primarily focuses on safety. Researchers are still gathering information on how well NALIRIFOX is tolerated specifically for small intestine and appendiceal cancers. However, past studies provide initial evidence that the treatment can be safely administered under medical supervision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about NALIRIFOX for appendiceal and small intestine cancers because it combines nal-IRI (liposomal irinotecan) with 5-FU/LV, targeting cancer cells more effectively. This combination is unique because nal-IRI is designed to improve delivery and retention of the chemotherapy drug irinotecan specifically in tumors, potentially enhancing its effectiveness compared to traditional regimens like FOLFIRI or FOLFOX. Unlike standard treatments, NALIRIFOX aims to provide a more focused attack on cancer cells, which could lead to better outcomes and fewer side effects.

What evidence suggests that NALIRIFOX might be an effective treatment for appendiceal and small intestine cancers?

Research has shown that NALIRIFOX, a combination of three drugs, has potential in treating certain cancers. In a previous study, this treatment helped patients with pancreatic cancer live longer compared to other treatments. This trial will evaluate NALIRIFOX for its effectiveness in treating cancers of the small intestine and appendix. The treatment targets cancer cells with drugs that stop them from growing and spreading. While NALIRIFOX has demonstrated some effectiveness in fighting cancer, more research is needed to confirm its benefits for small intestine and appendix cancers. ^{1 2 3 4 6}

Who Is on the Research Team?

Abdullah Esmail, MD

Principal Investigator

Houston Methodist Nael Cancer Center

Are You a Good Fit for This Trial?

Adults with advanced small intestine or appendiceal cancers, either mucinous or non-mucinous types, are eligible for this trial. They must have a confirmed diagnosis and be ready to start first-line chemotherapy.

Inclusion Criteria

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

Life expectancy ≥6 months

My cancer originates from the appendix or small intestine.

Exclusion Criteria

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

I haven't had cancer or cancer treatment in the last 5 years.

Hematology laboratory values of: Absolute neutrophil count ≤1500 cells/mm3, Platelets ≤100,000 cells/mm3, Hemoglobin ≤9 g/dL, White blood count ≤3000 cells/mm3

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NALIRIFOX (liposomal irinotecan, 5-FU, LV, and oxaliplatin) every 2 weeks for 12 months

12 months

Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NALIRIFOX

Trial Overview The trial is testing NALIRIFOX as the initial treatment regimen. This includes liposomal irinotecan, fluorouracil (5-FU), leucovorin (LV), and oxaliplatin administered intravenously every two weeks over a year.

How Is the Trial Designed?

Group I: nal-IRI plus 5-FU/LV plus NALIRIFOX Experimental Treatment 1 Intervention

Patients in this arm will receive NALIRIFOX

Group II: Historical Control Arm Active Control 1 Intervention

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07060014

NALIRIFOX (Nal-IRI Plus 5-FU/LV Plus Oxaliplatin) as First ... 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 ...

2. smartpatients.com smartpatients.com/trials/NCT07060014

NALIRIFOX (Nal-IRI Plus 5-FU/LV Plus Oxaliplatin) as First- ... 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 ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0959804925002059

Phase 1/2 study of liposomal irinotecan plus S-1 for ... The phase 3 NAPOLI-1 trial showed that the liposomal irinotecan (nal-IRI) plus fluorouracil/folinic acid (5-FU/LV) regimen improved OS compared ...

4. ctv.veeva.com ctv.veeva.com/study/nalirifox-nal-iri-plus-5-fu-lv-plus-oxaliplatin-as-first-line-treatment-for-patients-with-advanced

NALIRIFOX (Nal-IRI Plus 5-FU/LV Plus Oxaliplatin) as First ... This study will evaluate the safety and efficacy of NALIRIFOX per NAPOLI-3 regimen as first-line chemotherapy for patients with advanced ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7774735/

nal‐IRI+5‐FU/LV versus 5‐FU/LV in post‐gemcitabine ... In the nal‐IRI+5‐FU/LV arm, 61% of grade ≥3 TEAEs were judged as treatment‐related, versus 21% in the 5‐FU/LV arm, with decreased neutrophil ...

6. withpower.com withpower.com/trial/phase-1-appendiceal-cancers-6-2025-16307

NALIRIFOX for Appendiceal and Small Intestine Cancers 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 ...