Chemotherapy Combination for Pancreatic Cancer

(NAPOLI 3 Trial)

No longer recruiting at 272 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ipsen

Must not be taking: CYP3A inhibitors, CYP2C8 inducers

Disqualifiers: CNS metastases, Second malignancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 12

Duration: Until progression or unacceptable toxicity

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a new combination of chemotherapy drugs for individuals with metastatic pancreatic cancer. It compares the addition of Irinotecan liposome injection to a mix of other cancer drugs against the standard treatment of nab-paclitaxel and gemcitabine. Participants must have metastatic pancreatic cancer that has not yet been treated in this advanced stage. The study seeks to find ways to extend survival for those facing this challenging condition. As a Phase 3 trial, it represents the final step before FDA approval, providing participants an opportunity to contribute to potentially groundbreaking treatment advancements.

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

The trial does not specify if you need to stop your current medications, but it does exclude those using strong inhibitors or inducers of certain enzymes (CYP3A, CYP2C8, and UGT1A1). It's best to discuss your current medications with the trial team.

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

Research has shown that the combination of nab-paclitaxel and gemcitabine is generally safe for treating pancreatic cancer. This combination has received approval for use, indicating thorough testing. Common side effects include tiredness and low blood counts, but these are usually manageable.

In studies, a treatment using irinotecan liposome injection with oxaliplatin and 5-FU/LV (a mix of chemotherapy drugs) showed promising results. Patients tolerated it well, with side effects similar to other cancer drugs, such as nausea and low white blood cell counts.

Both treatments have demonstrated sufficient safety in past studies to warrant further testing. Serious side effects are uncommon, but they can occur. It is important to discuss with a doctor what to expect and whether these treatments are suitable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for pancreatic cancer because they involve unique combinations that may offer new hope to patients. Unlike the standard chemotherapy options, the combination of nab-paclitaxel and gemcitabine is administered on a more frequent schedule, which could enhance its effectiveness against cancer cells. Additionally, the combination of irinotecan liposome injection, oxaliplatin, and 5-FU/LV offers a novel approach by utilizing liposomal technology to improve drug delivery and potency. These innovative strategies aim to combat the cancer more aggressively and potentially improve patient outcomes.

What evidence suggests that this trial's treatments could be effective for metastatic pancreatic cancer?

In this trial, participants will receive one of two treatment combinations. Studies have shown that the combination of nab-paclitaxel and gemcitabine, one of the treatment arms, can extend the lives of patients with advanced pancreatic cancer. This combination reduces the risk of cancer progression or death by 31%. The other treatment arm includes irinotecan liposome injections with oxaliplatin and 5-FU/LV, a mix of cancer-fighting drugs. Research suggests this combination is promising, as previous trials found it effective and manageable for those with advanced pancreatic cancer. Both treatment options in this trial offer hope for improving survival rates in pancreatic cancer patients. ^{1 2 4 5 6}

Who Is on the Research Team?

Ipsen Medical Director

Principal Investigator

Ipsen

Are You a Good Fit for This Trial?

This trial is for adults with a recent diagnosis of metastatic pancreatic cancer who haven't been treated for it before. They should have measurable tumors, be in good physical condition (ECOG 0 or 1), and have normal blood counts, liver and kidney function. People can't join if they've had only localized disease, certain other cancers within the last two years, or used strong drug inhibitors/inducers recently.

Inclusion Criteria

I have at least one cancer spot that can be measured on a scan.

My kidneys work well enough, with a creatinine clearance rate of at least 30 mL/min.

My pancreatic cancer is confirmed and untreated in its advanced stage.

Exclusion Criteria

My body has low or no DPD enzyme activity.

I have a history of cancer spreading to my brain or spinal cord.

Concurrent illnesses that would be a relative contraindication to trial participation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive either Irinotecan liposome injection with 5-FU/LV and oxaliplatin or nab-paclitaxel with gemcitabine in 28-day cycles until progression or unacceptable toxicity

Until progression or unacceptable toxicity

3 visits per cycle (in-person)

Follow-up

Participants are monitored for overall survival and progression-free survival every 8 weeks after the first dose, and every 2 months after the end of treatment

Up to 893 days

Every 8 weeks, then every 2 months

What Are the Treatments Tested in This Trial?

Interventions

• 5Fluorouracil
• Gemcitabine
• Irinotecan Liposomal Injection
• Leucovorin
• Nab-paclitaxel
• Oxaliplatin

Trial Overview The study tests Irinotecan liposome injection combined with 5-fluorouracil/Leucovorin and Oxaliplatin against Nab-paclitaxel plus Gemcitabine treatment to see which is better at improving survival rates in patients with untreated metastatic pancreatic cancer.

How Is the Trial Designed?

Group I: Irinotecan liposome injection + Oxaliplatin + 5-FU/LV Experimental Treatment 4 Interventions

Irinotecan liposome injection, oxaliplatin, 5 FU/LV, will be administered on Days 1 and 15 of each 28-day cycle (until progression or unacceptable toxicity).

Group II: Nab-paclitaxel + Gemcitabine Active Control 2 Interventions

Nab-paclitaxel and gemcitabine will be administered on Days 1, 8 and 15 of each 28-day cycle (until progression or unacceptable toxicity).

5Fluorouracil is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Efudex for:

• Actinic keratosis
• Basal cell carcinoma

Approved in Canada as Efudex for:

• Actinic keratosis
• Basal cell carcinoma

Approved in United States as Adrucil for:

• Anal Cancer
• Breast Cancer
• Cervical Cancer
• Colorectal Cancer
• Nasopharyngeal Carcinoma
• Pancreatic Cancer
• Stomach Cancer

Approved in European Union as Fluorouracil for:

• Actinic keratosis
• Basal cell carcinoma
• Anal Cancer
• Breast Cancer
• Cervical Cancer
• Colorectal Cancer
• Nasopharyngeal Carcinoma
• Pancreatic Cancer
• Stomach Cancer

Who Is Running the Clinical Trial?

Ipsen

Lead 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. clinicaltrials.gov clinicaltrials.gov/study/NCT04083235

NCT04083235 | A Study to Assess the Effectiveness and ... The purpose of this study is to look at the efficacy and safety of Irinotecan liposome injection in combination with other approved drugs used for cancer ...

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/PMC7745557/

A phase II study of liposomal irinotecan with 5-fluorouracil ... A phase II study of liposomal irinotecan with 5-fluorouracil, leucovorin and oxaliplatin in patients with resectable pancreatic cancer: the nITRO trial.

4. nature.com nature.com/articles/s41392-024-01948-4

Irinotecan hydrochloride liposome HR070803 in ... HR070803 in combination with 5-FU/LV has shown promising efficacy and manageable safety in advanced or metastatic PDAC in the second-line setting.

5. mayo.edu mayo.edu/research/clinical-trials/cls-20503767

Clinical Trials The purpose of this study is to look at the effectiveness and safety of Irinotecan liposome injection in combination with other approved drugs used for cancer ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04083235?term=NCT04083235&viewType=Table&rank=1

A Study to Assess the Effectiveness and Safety ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...