Chemotherapy Combinations for Advanced Pancreatic Cancer

Recruiting at 762 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

176 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial compares two treatment combinations: gemcitabine hydrochloride and nab-paclitaxel, or fluorouracil, leucovorin calcium, and liposomal irinotecan in older patients with pancreatic cancer that has spread to other places in the body (metastatic). Drugs used in chemotherapy, such as gemcitabine hydrochloride, nab-paclitaxel, fluorouracil, leucovorin calcium, and liposomal irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This study may help doctors find out which treatment combination is better at prolonging life in older patients with metastatic pancreatic cancer.

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.

What data supports the effectiveness of the drug combinations for advanced pancreatic cancer?

The combination of nab-paclitaxel (a form of paclitaxel) and gemcitabine has shown substantial clinical activity and increased survival in patients with advanced pancreatic cancer. Additionally, liposomal irinotecan combined with 5-fluorouracil (5-FU) and leucovorin has been approved for use in patients with metastatic pancreatic cancer, showing improved survival compared to 5-FU and leucovorin alone. ^{1 2 3 4 5}

Is the chemotherapy combination for advanced pancreatic cancer safe for humans?

The chemotherapy combinations involving liposomal irinotecan, 5-fluorouracil, leucovorin, gemcitabine, and nab-paclitaxel have been shown to be generally well-tolerated in patients with advanced pancreatic cancer, according to several studies. These treatments have been evaluated for safety in clinical trials and real-world settings, indicating they are safe for human use in this context. ^{3 5 6 7 8}

What makes this drug combination unique for treating advanced pancreatic cancer?

This drug combination is unique because it uses nanoparticle formulations of paclitaxel and irinotecan, which can improve drug delivery and effectiveness. Additionally, combining these with gemcitabine and fluorouracil has shown increased survival rates compared to using gemcitabine alone. ^{1 3 9 10 11}

Research Team

Efrat Dotan

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

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.

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

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. Sweden pubmed.ncbi.nlm.nih.gov

[Nanoparticles for cancer therapy]. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

A case of pathological complete response with liposomal irinotecan + 5-FU/LV for unresectable locally advanced pancreatic cancer. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Long-Term Survival of a Patient With Peritoneal Carcinomatosis From Pancreatic Cancer Maintained by Nanoliposomal Irinotecan as Third-Line Chemotherapy. [2022]

5. England pubmed.ncbi.nlm.nih.gov

NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: Final overall survival analysis and characteristics of long-term survivors. [2022]

6. England 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. [2022]

7. England 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. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Nursing Implications of Chemotherapy Agents and Their Associated Side Effects in Patients With Pancreatic Cancer. [2017]

9. Germany pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Carfilzomib and Paclitaxel Co-Loaded Protein Nanoparticles an Effective Therapy Against Pancreatic Adenocarcinomas. [2022]

11. United States 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. [2023]