Chemotherapy Combinations for Advanced Pancreatic Cancer

Not currently recruiting at 782 trial locations

Overseen By Sandra Zagorski

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: ECOG-ACRIN Cancer Research Group

Must not be taking: CYP3A4 inhibitors, UGT1A1 inhibitors

Disqualifiers: Severe cognitive impairment, Frail, 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: Unknown

Duration: Varies, up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two chemotherapy combinations to determine which better helps older patients with advanced pancreatic cancer live longer. One group receives gemcitabine and nab-paclitaxel, while the other receives fluorouracil (also known as 5-Fluorouracil or 5-FU), leucovorin, and liposomal irinotecan. Researchers aim to discover which combination more effectively stops cancer cells from growing and spreading. Individuals recently diagnosed with metastatic pancreatic cancer who have not yet received treatment might be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial requires that you avoid taking any medications or substances that strongly affect certain liver enzymes (CYP3A4 and UGT1A1) while participating. If you are on such medications, you may need to stop or switch them.

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

Research shows that the combination of gemcitabine and nab-paclitaxel is generally well-tolerated by patients with pancreatic cancer. Studies have found this treatment effective, with manageable side effects for many patients. While some side effects may occur, they are usually considered acceptable given the treatment's benefits.

Similarly, the combination of fluorouracil, leucovorin, and liposomal irinotecan has a strong safety record. Previous studies indicate that this treatment is a viable option, even for patients with advanced cancer, and is generally well-tolerated. Again, while side effects can happen, the overall safety is considered satisfactory.

Healthcare providers closely monitor side effects for both treatment options and are prepared to manage them effectively. Participants in trials for these treatments can expect a reasonable level of safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for advanced pancreatic cancer because they combine chemotherapy drugs in innovative ways that could improve effectiveness. Arm A uses a combination of gemcitabine and nab-paclitaxel, which enhances the delivery of chemotherapy by using nab-paclitaxel to help gemcitabine penetrate tumors more effectively. Arm B combines fluorouracil with leucovorin and liposomal irinotecan, the latter of which is specially formulated to stay in the body longer, potentially increasing the drug's impact on cancer cells. These combinations aim to tackle the cancer more aggressively and could offer new hope for patients who may not respond well to existing treatments.

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

In this trial, participants will receive one of two chemotherapy combinations for advanced pancreatic cancer. Studies have shown that combining gemcitabine and nab-paclitaxel can extend patients' lives. Specifically, one study found that patients lived about 8.5 months on average with both drugs, compared to 6.7 months with just gemcitabine, suggesting the combination may improve survival.

The trial also tests a combination of fluorouracil, leucovorin, and liposomal irinotecan. Research indicates that patients receiving this combination lived about 7.8 months on average. Additionally, it helped control the disease in 56% of patients, with more than half experiencing a slowing of their cancer. Both drug combinations offer potential benefits for treating advanced pancreatic cancer. ^{1 4 6 7 8}

Who Is on the Research Team?

Efrat Dotan

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for older English-speaking patients with newly diagnosed, untreated metastatic pancreatic cancer. They must have adequate blood counts, organ function, and controlled HIV or hepatitis if present. Men must agree to avoid fathering children during the study. Patients should not be 'frail' as per geriatric assessment and cannot take certain drugs that affect chemotherapy metabolism.

Inclusion Criteria

I had hepatitis C but am cured, or I'm being treated with no detectable virus.

My kidney function is within the safe range for the study.

Your white blood cell count should be at least 1,500 per microliter of blood.

Exclusion Criteria

You do not live in the United States.

I haven't had any cancer except for skin cancer in the last 5 years.

I have chronic hepatitis B but it's not under control even with treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either gemcitabine and nab-paclitaxel or fluorouracil, leucovorin, and liposomal irinotecan. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Varies, up to 2 years

Bi-weekly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 3 months for 2 years

Quarterly visits

What Are the Treatments Tested in This Trial?

Interventions

• Fluorouracil
• Gemcitabine
• Liposomal Irinotecan
• Nab-paclitaxel

Trial Overview

The trial compares two chemotherapy combinations: gemcitabine hydrochloride with nab-paclitaxel versus fluorouracil with leucovorin calcium and liposomal irinotecan. It aims to determine which combination better prolongs life in older patients with metastatic pancreatic cancer.

How Is the Trial Designed?

Group I: Arm B (fluorouracil, leucovorin, liposomal irinotecan) Experimental Treatment 6 Interventions

Patients receive fluorouracil IV over 46 hours starting on day 1. Patients also receive leucovorin IV over 90-120 minutes and liposomal irinotecan IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm A (gemcitabine, nab-paclitaxel) Experimental Treatment 5 Interventions

Patients receive gemcitabine IV over 30 minutes and nab-paclitaxel IV over 30 minutes on day 1. Cycles repeat every 14 days 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?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Nanoparticles show great potential in cancer therapy and diagnosis, but there is a significant gap between experimental research and clinical application, with only a few formulations currently in use.

Notable examples of nanoparticle therapies include nanoparticle-albumin-bound paclitaxel and liposomal irinotecan, both of which are approved for treating pancreatic cancer, demonstrating their efficacy in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nanoparticles for cancer therapy]. Löhr, M., van der Wijngaart, W., Fagerberg, B.[2019]

In a phase 3 trial involving 861 patients with metastatic pancreatic cancer, the combination of nab-paclitaxel and gemcitabine significantly improved overall survival (8.5 months) compared to gemcitabine alone (6.7 months), with a hazard ratio for death of 0.72, indicating a 28% reduction in the risk of death.

The combination therapy also resulted in better progression-free survival (5.5 months vs. 3.7 months) and a higher overall response rate (23% vs. 7%), although it was associated with increased rates of adverse events like neutropenia and neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. Von Hoff, DD., Ervin, T., Arena, FP., et al.[2022]

In a real-world study of 86 patients with metastatic pancreatic adenocarcinoma who received nal-IRI plus 5-FU/LV after gemcitabine therapy, the median overall survival was 9.4 months, indicating that this treatment is effective in this patient population.

The treatment was generally well-tolerated, with the most common severe side effects being neutropenia (37.2%) and nausea (10.5%), suggesting a manageable safety profile similar to findings from the NAPOLI-1 trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world efficacy and safety of liposomal irinotecan plus fluorouracil/leucovorin in patients with metastatic pancreatic adenocarcinoma: a study by the Korean Cancer Study Group. Yoo, C., Im, HS., Kim, KP., et al.[2022]

A study of 5465 patients with advanced pancreatic cancer in Ontario showed that the introduction of new chemotherapy regimens, GEMNAB and FOLFIRINOX, significantly improved overall survival rates over time, with median survival increasing from 5.6 months to 7.6 months between 2008 and 2018.

FOLFIRINOX was found to provide better overall survival compared to GEMNAB, particularly in younger and healthier patients, while GEMNAB still showed improved survival compared to the older standard treatment, gemcitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer. Raphael, MJ., Raskin, W., Habbous, S., et al.[2023]

In a study of 128 patients with metastatic pancreatic adenocarcinoma, nal-IRI combined with 5-FU/LV showed a median overall survival of 4.9 months and a median progression-free survival of 2.4 months when used as a third-line or later treatment after standard therapies.

Patients with better performance status (ECOG 0) had significantly longer survival rates, indicating that nal-IRI plus 5-FU/LV may be particularly effective for those in good health or with favorable prior treatment responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real-world analysis of nanoliposomal-irinotecan with 5-fluorouracil and folinic acid as third- or later-line therapy in patients with metastatic pancreatic adenocarcinoma. Chun, JW., Woo, SM., Lee, SH., et al.[2022]

Recent treatment regimens for advanced pancreatic cancer, including gemcitabine, FOLFIRINOX, and nab-paclitaxel, have shown varying levels of efficacy, highlighting the importance of understanding their unique safety profiles.

Nurses play a crucial role in patient education and symptom management, as each treatment regimen has different adverse events that need to be identified and managed effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nursing Implications of Chemotherapy Agents and Their Associated Side Effects in Patients With Pancreatic Cancer. Hronek, JW., Reed, M.[2017]

The combination of nab-paclitaxel, gemcitabine, and capecitabine was found to be well tolerated in a phase I study with 15 patients, establishing a maximum-tolerated dose (MTD) but showing only modest antitumor activity in metastatic pancreatic cancer.

Despite the regimen being generally safe, with a low incidence of severe hematologic toxicities, only 14.3% of patients had a partial response, indicating that optimizing dose intensity may be crucial for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. Ko, AH., Truong, TG., Kantoff, E., et al.[2022]

Citations

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Tumor response rates to liposomal irinotecan + 5-FU/LV were partial response in 3%, stable disease in 23%, and progressive disease in 74%, with ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11871866/

Outcomes of Liposomal Irinotecan With 5‐FU and ...

In this study, the median overall survival (OS) was significantly longer in the liposomal irinotecan plus 5-FU/LV group compared to the 5-FU/LV ...

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ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e16260

Survival outcomes of liposomal irinotecan in patients with ...

The median overall survival (mOS) was 5.9 (95% CI 3.5 – 8.2) months, and the 6-month OS rate was 48.7%. The median interval between the ...

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asco.org

asco.org/abstracts-presentations/ABSTRACT320565

Efficacy and safety of liposomal irinotecan plus fluorouracil ...

Objective response rate of nal-IRI + 5-FU/LV was 2.9% (1 partial response) and stable disease was achieved in 31.4% (n = 11). With median follow-up duration of ...

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sciencedirect.com

sciencedirect.com/science/article/pii/S2949819825000196

Nanoliposomal irinotecan with fluorouracil and folinic acid ...

The median OS was 7.8 months; median progression-free survival was 3.7 months; median overall response rate was 11%; and median disease control rate was 56%.

6.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e16263

A pilot study of liposomal irinotecan plus 5-FU/LV ...

Administration of paricalcitol in combination with liposomal irinotecan and 5-FU/LV is well tolerated in patients with advanced pancreatic cancer.

7.

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 ...

8.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S104084282400129X

Safety and efficacy of liposomal irinotecan as the second- ...

Second-line treatments based on nal-IRI exhibited significantly improved PFS, OS, and ORR compared to other available treatments in advanced pancreatic cancer.