NALIRIFOX for Small Bowel Cancer

Recruiting at 4 trial locations

Overseen By Tiago Biachi de Castria, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Tiago Biachi de Castria

Must not be taking: CYP3A inhibitors, CYP2C8 inducers

Disqualifiers: CNS metastases, Gastrointestinal disorders, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

Duration: 24 weeks

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called NALIRIFOX for individuals with small bowel cancer that has spread. NALIRIFOX combines 5-fluorouracil, Leucovorin, Nanoliposomal irinotecan, and Oxaliplatin. The goal is to evaluate how effectively this drug combination controls cancer and improves patient outcomes. Participants will receive the treatment through an IV on specific days of a 28-day cycle, with the option to continue with a modified treatment based on their response. Suitable candidates have confirmed small bowel adenocarcinoma that has not been treated in the metastatic setting and have one or more measurable metastatic lesions. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires participants to stop using strong inhibitors or inducers of certain enzymes (CYP3A, CYP2C8, and UGT1A1) at least 1-2 weeks before joining. If you're on these medications, you may need to stop them, but it's best to discuss with your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research on NALIRIFOX has revealed important safety findings. NALIRIFOX combines four drugs: nanoliposomal irinotecan, oxaliplatin, leucovorin, and 5-fluorouracil (5-FU). Studies indicate that this combination is generally well-tolerated, though it can have side effects, like many cancer treatments.

One study found that patients experienced side effects such as nausea, tiredness, and diarrhea, which were often manageable with standard care. Another study noted that the safety profile aligned with expectations for these types of cancer drugs, meaning most side effects were known and controllable.

While no treatment is without risk, existing research suggests that NALIRIFOX is reasonably safe for patients. It is important to discuss potential risks and benefits with a doctor before joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for small bowel cancer?

Unlike the standard chemotherapy regimens for small bowel cancer, which often include combinations like FOLFOX or FOLFIRI, NALIRIFOX introduces a unique formulation with nanoliposomal irinotecan that enhances drug delivery to tumors. This liposomal delivery system potentially increases the effectiveness of irinotecan by improving its absorption and targeting, while reducing side effects. Researchers are excited because this approach could offer a more efficient and tolerable treatment option, potentially leading to better outcomes for patients with small bowel cancer.

What evidence suggests that NALIRIFOX might be an effective treatment for small bowel cancer?

This trial will evaluate NALIRIFOX, a combination of four cancer-fighting drugs, for its potential to treat small bowel cancer. Studies have shown that NALIRIFOX can shrink tumors and extend the lives of patients with advanced cancers. In one study, patients taking NALIRIFOX experienced tumor reduction and manageable side effects. Another study found that even at lower doses, the treatment remained effective for some cancer types. These findings suggest NALIRIFOX might benefit small bowel cancer, but further research is needed to confirm its effectiveness for this specific condition. ^{1 2 3 6 7}

Who Is on the Research Team?

Tiago Biachi de Castria, MD, PhD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced small bowel cancer that can't be surgically removed. Participants must have measurable disease, adequate organ function, and no prior chemotherapy for metastatic disease. They cannot join if they've had recent surgery or radiation, significant heart disease, another active cancer, or known allergies to the drugs being tested.

Inclusion Criteria

Subjects infected with HIV must meet specific criteria.

Electrocardiogram (ECG) without any clinically significant findings.

I have taken a pregnancy test recently and it was negative.

Exclusion Criteria

My cancer started in the ampulla or appendix.

Pregnant or breastfeeding.

I have a serious stomach or intestine condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NALIRIFOX treatment on Day 1 and Day 15 of each 28-day cycle for up to 6 cycles

24 weeks

12 visits (in-person)

De-escalated Maintenance

Based on response, participants may continue with NALIRIFOX minus oxaliplatin until progression or intolerable toxicity

Until progression or intolerable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• 5 fluorouracil
• Leucovorin
• Nanoliposomal irinotecan
• Oxaliplatin

Trial Overview The study tests a combination of four IV drugs (NALIRIFOX): nanoliposomal irinotecan, oxaliplatin, leucovorin, and 5-FU given every two weeks in a 28-day cycle. After six cycles of full treatment, patients may receive maintenance therapy without oxaliplatin if their doctor agrees.

How Is the Trial Designed?

Group I: NALIRIFOX and De-escalated maintenance Experimental Treatment 4 Interventions

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.

Who Is Running the Clinical Trial?

Tiago Biachi de Castria

Lead Sponsor

Trials

1

Recruited

40+

H. Lee Moffitt Cancer Center and Research Institute

Collaborator

Trials

576

Recruited

145,000+

Ipsen

Industry Sponsor

Trials

358

Recruited

74,600+

David Loew

Ipsen

Chief Executive Officer since 2020

BA in Business Administration and MBA from the University of St. Gallen, Switzerland

Sandra Silvestri

Ipsen

Chief Medical Officer since 2023

MD, PhD

Published Research Related to This Trial

A phase II study involving 43 patients with advanced gastrointestinal tumors showed that capecitabine combined with either irinotecan or oxaliplatin is effective in treating colorectal and other GI cancers, demonstrating significant clinical activity as both first-line and salvage therapy.

The combination therapies exhibited an excellent safety profile, with manageable grade 3/4 toxicities primarily limited to diarrhea, and no severe myelosuppression observed, indicating that these regimens are safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of capecitabine/irinotecan and capecitabine/oxaliplatin in advanced gastrointestinal cancers. Jordan, K., Kellner, O., Kegel, T., et al.[2019]

The combination of FOLFOXIRI (oxaliplatin, irinotecan, fluorouracil, and leucovorin) with the biologic agent panitumumab has shown improved outcomes in metastatic colorectal cancer (mCRC) patients, based on randomized clinical trial results.

While FOLFOXIRI combined with bevacizumab has extensive data from large trials, its true benefit is still uncertain as it hasn't been tested in a randomized setting, highlighting the need for further research to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFOXIRI plus biologics in advanced colorectal cancer. García-Alfonso, P., Torres, G., García, G., et al.[2020]

The mFOLFOXIRI regimen, a combination of 5-fluorouracil, oxaliplatin, and irinotecan, was found to be safe for patients with advanced colorectal cancer, with no treatment-related deaths reported despite some serious adverse events like intestinal perforation and neutropenia.

In terms of efficacy, the regimen showed a promising overall response rate of 63.8% in patients with metastatic colorectal cancer, with significantly better outcomes for those who completed more than four cycles of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Analysis on safety and preliminary efficacy of dose-modified regimen of 5-fluorouracil plus oxaliplatin and irinotecan (FOLFOXIRI) in advanced colorectal cancer]. Cai, Y., Deng, R., Hu, H., et al.[2018]

Liposomal irinotecan (Irinophore C™) demonstrated significant efficacy as a single agent in treating colorectal cancer, delaying tumor growth more effectively than the combination with 5-fluorouracil (5-FU).

The combination of IrC™ and 5-FU resulted in increased toxicity and altered pharmacokinetics of 5-FU, suggesting that while IrC™ is a promising treatment, its use with 5-FU may complicate treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of colorectal cancer using a combination of liposomal irinotecan (Irinophore C™) and 5-fluorouracil. Hare, JI., Neijzen, RW., Anantha, M., et al.[2021]

In a phase II study involving 24 patients with metastatic or recurrent small bowel adenocarcinoma, the mFOLFOX6 chemotherapy regimen demonstrated a 1-year progression-free survival (PFS) rate of 23.3%, indicating some efficacy as a first-line treatment.

The treatment was generally well tolerated, with no treatment-related deaths reported, although significant side effects included neutropenia (38%) and anemia/peripheral neuropathy (25%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of 5-fluorouracil/L-leucovorin/oxaliplatin (mFOLFOX6) in Japanese patients with metastatic or unresectable small bowel adenocarcinoma. Horimatsu, T., Nakayama, N., Moriwaki, T., et al.[2022]

In a study of 36 patients with advanced colorectal cancer who had previously been treated with fluoropyrimidines, the combination of irinotecan and oxaliplatin showed a 42% overall response rate, indicating significant antitumor activity.

The treatment was generally well-tolerated, with manageable side effects; severe hematologic toxicity was rare, and the most common nonhematologic issues were nausea and diarrhea, suggesting that this regimen could be a viable option for patients with progressive disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined irinotecan and oxaliplatin plus granulocyte colony-stimulating factor in patients with advanced fluoropyrimidine/leucovorin-pretreated colorectal cancer. Scheithauer, W., Kornek, GV., Raderer, M., et al.[2018]

The study established the maximum tolerated dose (MTD) for the combination treatment NALIRIFOX in patients with metastatic pancreatic ductal adenocarcinoma, with 32 out of 56 patients receiving the MTD, indicating a manageable safety profile despite some patients experiencing severe treatment-related adverse events.

Patients treated with NALIRIFOX showed a median progression-free survival of 9.2 months and overall survival of 12.6 months, suggesting that this treatment regimen may be effective for this difficult-to-treat cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line liposomal irinotecan with oxaliplatin, 5-fluorouracil and leucovorin (NALIRIFOX) in pancreatic ductal adenocarcinoma: A phase I/II study. Wainberg, ZA., Bekaii-Saab, T., Boland, PM., et al.[2021]

In a study of 20 patients with advanced small bowel adenocarcinoma, chemotherapy combining 5-fluorouracil (5-FU) with platinum compounds showed a 21% overall response rate, with median progression-free survival of 8 months and overall survival of 14 months, indicating moderate efficacy and tolerability.

The combination of 5-FU and irinotecan demonstrated promising results, with 50% of patients achieving disease stabilization and one patient experiencing a complete biological response, suggesting that this combination warrants further investigation as a first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination chemotherapy in advanced small bowel adenocarcinoma. Locher, C., Malka, D., Boige, V., et al.[2022]

Chemotherapy agents like fluorouracil and oxaliplatin can cause significant side effects in colorectal cancer treatment, but strategies like therapeutic drug monitoring and chronomodulation have shown promise in reducing these adverse effects in clinical trials.

Supportive measures, including specific medications and schedule adjustments, are essential for managing side effects such as myelosuppression and nausea, emphasizing the need for individualized patient care and teamwork among healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of chemotherapy-induced adverse effects in the treatment of colorectal cancer. Jansman, FG., Sleijfer, DT., de Graaf, JC., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06835387

NCT06835387 | Study of NALIRIFOX in Advanced ... 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 ...

2. ascopubs.org ascopubs.org/doi/10.1200/OA-25-00047

Phase II Study of Liposomal Irinotecan in Combination With ... We investigated the efficacy, safety, and tolerability of liposomal irinotecan in combination with oxaliplatin, leucovorin, and fluorouracil as ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9434681/

A real-world analysis of nanoliposomal-irinotecan with 5- ... The aim of this study was to evaluate the effectiveness and safety of nal-IRI with 5-FU/LV for use beyond second-line treatment after standard frontline ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT433568

Results of a phase II, open-label pilot study evaluating ... A phase II, open-label, pilot study evaluating the safety and activity of liposomal irinotecan (Nal-IRI) in combination with 5-FU and oxaliplatin (NALIRIFOX) in ...

5. targetedonc.com targetedonc.com/view/nalirifox-dose-reductions-maintain-efficacy-in-pancreatic-cancer

NALIRIFOX Dose Reductions Maintain Efficacy in ... During a live event, Kashif Ali, MD, discussed outcomes from the NAPOLI 3 trial in terms of efficacy, tolerability, and dose modification.

6. asco.org asco.org/abstracts-presentations/ABSTRACT390940

A randomized, open-label phase 3 study of liposomal ... NAPOLI-3: A randomized, open-label phase 3 study of liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin (NALIRIFOX) versus nab-paclitaxel + ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0959804924008505

Liposomal irinotecan, oxaliplatin, and S-1 as first-line ... NASOX exhibited a manageable safety profile and encouraging efficacy outcomes consistent with NALIRIFOX, showing potential to replace infusional 5-fluorouracil ...