Chemotherapy for Pancreatic Neuroendocrine Carcinoma

No longer recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Roswell Park Cancer Institute

Must not be taking: Steroids, Investigational therapy

Disqualifiers: CNS metastases, DPD deficiency, HIV, 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: 1

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of chemotherapy drugs to evaluate their effectiveness against a specific type of aggressive cancer that originates in the pancreas or other parts of the digestive system and has spread despite treatment. The drugs under investigation, including liposomal irinotecan, leucovorin, and fluorouracil (also known as 5-Fluorouracil or 5-FU), aim to halt or slow the growth and spread of cancer cells. Suitable candidates for this trial are those with advanced pancreatic or gastrointestinal neuroendocrine cancer who have not responded to previous treatments. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants, providing an opportunity to contribute to potentially effective cancer therapies.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research has shown that the combination of liposomal irinotecan, leucovorin, and fluorouracil is generally safe. Studies suggest this treatment can be an option even for patients who have difficulty with daily activities. Patients with advanced pancreatic cancer usually tolerate this combination well in terms of side effects. Like most cancer treatments, it may still cause tiredness or nausea. However, the treatment is considered safe for patients with advanced conditions, meaning that while some side effects might occur, they typically do not outweigh the potential benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment combination of liposomal irinotecan, leucovorin, and fluorouracil for pancreatic neuroendocrine carcinoma because it offers a novel delivery system and mechanism of action. Unlike standard chemotherapy options, like streptozocin and everolimus, this treatment uses liposomal irinotecan, which enhances the delivery of the drug directly to the tumor cells, potentially increasing effectiveness while minimizing side effects. The treatment's schedule, with administration on days 1 and 15 over a 28-day cycle, is designed to optimize patient convenience and reduce toxicity, offering a promising new approach in the fight against this challenging cancer.

What evidence suggests that this treatment might be an effective treatment for neuroendocrine cancer?

This trial will evaluate a combination treatment of liposomal irinotecan, leucovorin, and fluorouracil for pancreatic neuroendocrine carcinoma. Research has shown that liposomal irinotecan, also known as Onivyde, can help treat metastatic pancreatic cancer, with studies finding it can extend patient survival. Fluorouracil, another drug in this trial, has effectively slowed the growth of metastatic pancreatic neuroendocrine tumors. Leucovorin, when combined with other chemotherapy drugs, has also proven effective in treating advanced pancreatic cancer. Together, these drugs stop cancer cells from growing and spreading, offering hope in treating high-grade neuroendocrine cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Renuka V. Iyer

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with advanced high grade neuroendocrine cancer of the GI tract, pancreas, or unknown origin that's resistant to treatment and has spread. They must have certain blood cell counts, organ function levels within set limits, a life expectancy of at least 12 weeks, agree to use contraception if applicable, and not be pregnant. Participants need measurable disease per RECIST criteria and can't have untreated brain metastases or certain serious health conditions.

Inclusion Criteria

Your liver enzymes (AST and ALT) are not too high. If you have liver metastases, the enzymes can be a little higher, but not too much.

Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

Your hemoglobin level is at least 9 grams per deciliter.

Exclusion Criteria

Any condition which in the Investigator?s opinion deems the participant an unsuitable candidate to receive study drug.

I do not have any serious illnesses that would stop me from following the study's requirements.

I have stable brain metastases, not on steroids for 7 days, and no carcinomatous meningitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive liposomal irinotecan, leucovorin, and fluorouracil intravenously on days 1 and 15 of each 28-day cycle

Up to 3 years

Visits on days 1 and 15 of each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

30 days, then every 2 months

What Are the Treatments Tested in This Trial?

Interventions

• Fluorouracil
• Leucovorin
• Liposomal Irinotecan

Trial Overview The study tests liposomal irinotecan combined with fluorouracil and leucovorin in patients whose cancer hasn't responded to other treatments. It aims to see if this combination can stop tumor growth by blocking enzymes needed for cell growth and spreading. The trial includes quality-of-life assessments as well.

How Is the Trial Designed?

Group I: Treatment (liposomal irinotecan, leucovorin, fluorouracil) Experimental Treatment 4 Interventions

Patients receive liposomal irinotecan IV over 90 minutes, leucovorin IV over 30 minutes, and fluorouracil IV over 46 hours on days 1 and 15. Courses repeat every 28 days for in the absence of disease progression or unacceptable toxicity.

Fluorouracil is already approved in United States, European Union, Canada for the following indications:

Approved in United States as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Skin cancer

Approved in European Union as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Approved in Canada as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

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

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8797514/

Long-term treatment with streptozocin/5-fluorouracil ... We report about 3 therapy-naïve patients with metastatic G2 (Ki67 10%–15%) pNETs treated with STZ/5-FU, that achieved sustained disease control for longer than ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0305737225000210

The efficacy of streptozotocin in managing pancreatic ... This review observed a median DCR of 87.5 % and a median ORR of 40 % for the triplet chemotherapy regimen of STZ, 5-FU, and doxorubicin. For doublet ...

3. ar.iiarjournals.org ar.iiarjournals.org/content/41/4/2071

Efficacy of FOLFOX Chemotherapy in Metastatic ... This retrospective study aimed to analyze the outcome of metastatic enteropancreatic NETs patients treated with FOLFOX.

4. journals.lww.com journals.lww.com/md-journal/fulltext/2022/01280/long_term_treatment_with.12.aspx

Long-term treatment with streptozocin/5-fluorouracil... We report about 3 therapy-naïve patients with metastatic G2 (Ki67 10%–15%) pNETs treated with STZ/5-FU, that achieved sustained disease control for longer than ...

5. mdpi.com mdpi.com/2077-0383/12/2/717

Chemotherapy in Well Differentiated Neuroendocrine ... This narrative review aims to summarize available evidence about the use of chemotherapy in the setting of G1-2 NETs and G3 NETs.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40034960/

Outcomes of Liposomal Irinotecan With 5-FU and ... Liposomal irinotecan plus 5-FU/LV regimen is a feasible second-line treatment option for PDAC patients with borderline performance status, with a safety ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03736720

NCT03736720 | Liposomal Irinotecan, Fluorouracil and ... This phase II trial studies how well liposomal irinotecan, leucovorin, and fluorouracil work in treating patients with high grade neuroendocrine cancer of ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.4_suppl.646

A randomised, phase II trial of liposomal irinotecan (nal-IRI) ... nal-IRI/5-FU/folinic acid, but not docetaxel, met the primary endpoint of 6 month (mo) progression-free survival (PFS) rate in pts with progressive PD-EP-NEC.

9. esmogastro.org esmogastro.org/article/S2949-8198(25)00019-6/fulltext

Nanoliposomal irinotecan with fluorouracil and folinic acid in ... NFF has an appropriate efficacy and safety profile for patients with unresectable pancreatic cancer. •. NFF is a candidate for second- or later- ...

10. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1250136/full

Clinical outcomes of liposomal irinotecan in advanced ... This real-world study aimed to evaluate the efficacy and safety of nal-IRI plus 5FU-LV in advanced PAC patients who progressed on conventional IRI-containing ...