Neoadjuvant Chemotherapy for Pancreatic Cancer

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Wake Forest University Health Sciences

Must not be taking: Investigational agents

Disqualifiers: Prior chemotherapy, Recent malignancy, Infections, 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

64 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new sequence of chemotherapy drugs for people with pancreatic cancer. It examines the effects—both positive and negative—of administering Gemcitabine (Gemzar) and nab-Paclitaxel (Abraxane) first, followed by mFOLFIRINOX (modified FOLFIRINOX). While these are standard treatments, they are not typically used in this order. The researchers aim to determine if this sequence can improve outcomes for those with borderline resectable or locally advanced pancreatic adenocarcinoma. Participants must have a confirmed diagnosis of pancreatic adenocarcinoma and meet specific health criteria. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

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

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

Research has shown that using Gemcitabine, Nab-paclitaxel, and mFOLFIRINOX together is generally safe for treating pancreatic cancer. Studies have compared these treatments to evaluate their effectiveness and safety. Both Nab-paclitaxel with Gemcitabine and mFOLFIRINOX have proven effective for advanced pancreatic cancer and have received FDA approval for this use.

Although these drugs are potent, they can cause side effects such as tiredness, nausea, and low blood cell counts. These side effects are common with chemotherapy and can usually be managed. These treatments have been used for a long time, providing a solid understanding of their safety.

Overall, the treatments are considered well-tolerated. Testing the order of these treatments in the trial is a crucial step to further explore their potential benefits and risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for pancreatic cancer involve chemotherapy regimens like FOLFIRINOX and gemcitabine with nab-paclitaxel. However, this new approach combines both these regimens in a unique sequence to maximize effectiveness. Researchers are excited because it starts with gemcitabine and nab-paclitaxel to shrink the tumor, then switches to mFOLFIRINOX, a potent combo of drugs, aiming for better tumor reduction before surgery. This strategic sequencing could potentially improve outcomes by hitting the cancer with a broader spectrum of chemotherapy agents.

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

In this trial, participants will receive a treatment regimen starting with Gemcitabine and nab-Paclitaxel, followed by mFOLFIRINOX, to evaluate its effectiveness for treating pancreatic cancer. Research has shown that starting with Gemcitabine and nab-Paclitaxel, followed by mFOLFIRINOX, can help patients live longer and increase the chances of successful surgery after treatment. The FDA has already approved Gemcitabine and nab-Paclitaxel for advanced pancreatic cancer, confirming their effectiveness together. FOLFIRINOX, another approved treatment, is also associated with better survival and more successful surgeries for some patients. While using these treatments in this specific order is new, each has proven benefits, making this approach promising for patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Ravi K Paluri, MD

Principal Investigator

Wake Forest Baptist Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with borderline resectable or locally advanced pancreatic adenocarcinoma. Participants must be in good physical condition (ECOG 0-1), have adequate organ and marrow function, and not have had prior chemotherapy for pancreatic cancer. They should understand the study and consent to participate.

Inclusion Criteria

I am fully active or can carry out light work.

My blood and organ functions meet the required levels for the trial.

I can understand and am willing to sign the consent form.

Exclusion Criteria

I haven't had cancer in the last 3 years, except for certain skin, cervical, or low-risk prostate cancers.

Patients receiving any other investigational anti-neoplastic agents

I have had chemotherapy with gemcitabine, nab-paclitaxel, or FOLFIRINOX for pancreatic cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive Gemcitabine - Abraxane (nab-Paclitaxel) followed by mFOLFIRINOX

8 weeks

Weekly visits for chemotherapy administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine
• mFOLFIRINOX
• Nab paclitaxel

Trial Overview The trial tests a sequence of chemotherapy treatments: Gemcitabine - Abraxane followed by mFOLFIRINOX, which are FDA-approved individually but not as a combined treatment for this type of cancer. The effect of this sequence on patients' conditions is being studied.

How Is the Trial Designed?

Group I: Neoadjuvant Chemotherapy (Gemcitabine and nab-Paclitaxel and mFOLFIRNIOX) Experimental Treatment 4 Interventions

* Gemcitabine (1000 mg/m2 weekly, on day 1,8 and 15 OR 1000 mg/m2 weekly, on day 1 and 15 over 30 minutes after nab-paclitaxel infusion. * nab-Paclitaxel (125 mg/m2 weekly, on days 1,8, and 15 OR on days 1 and 15 as a 30-40 minute infusion administered first) for one month and then transition to mFOLFIRNIOX for one month 1 Cycle = 4 weeks: Day 1,8,15 in a 28 day cycle; 3 consecutive weeks (weeks 1, 2, and 3) of chemotherapy with 1 week off, OR 1 Cycle = 4 weeks: Day 1, 15 in a 28 day cycle; Every other week (weeks 1 and 3) of chemotherapy with 2nd and 4th week off * mFOLFIRINOX: Oxaliplatin, 85 mg/m² IV once every two weeks over 2 hours on Day 1 Irinotecan, 150 mg/m² IV once every two weeks over 90 minutes on Day 1 5-FU, 2,400 mg/m² IV once every two weeks over 46-48 hours administered via infusion Leucovorin, 400 mg/m2 IV every two weeks over 90 minutes on Day 1 1. Cycle = 4 weeks, administration on Day 1 and Day 15 of each mFOLIRINOX cycle

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

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 46 patients with resectable pancreatic ductal adenocarcinoma (PDAC) treated with modified FOLFIRINOX, pharmacokinetic-guided dosing of 5-Fluorouracil (5-FU) and Irinotecan (CPT-11) was associated with significantly longer progression-free survival.

Patients with a 5-FU area under the curve (AUC) above 28 mcg·h/mL and CPT-11 AUC below 10 mcg·h/mL had a reduced risk of disease progression, suggesting that tailored chemotherapy dosing can enhance treatment efficacy in PDAC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic drug monitoring of neoadjuvant mFOLFIRINOX in resected pancreatic ductal adenocarcinoma. Vilalta-Lacarra, A., Aldaz, A., Sala-Elarre, P., et al.[2023]

Modified FOLFIRINOX (mFOLFIRINOX) showed moderate efficacy in treating locally advanced or metastatic pancreatic cancer, with a response rate of 30.8% and a disease control rate of 69.2% in 13 patients after previous treatments failed.

The treatment was associated with a median overall survival of 176 days and significant adverse effects, including neutropenia in 38.5% of patients, indicating that while mFOLFIRINOX can be beneficial, it also carries risks that need to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified FOLFIRINOX for Locally Advanced and Metastatic Pancreatic Cancer Patients Resistant to Gemcitabine and S-1 in Japan: A Single Institutional Experience. Umemura, A., Nitta, H., Sasaki, A., et al.[2022]

In a study of 18 patients with locally advanced pancreatic cancer (LAPC), neoadjuvant therapy using FOLFIRINOX resulted in a promising R0 resection rate of 44%, indicating that a significant portion of patients became eligible for surgical removal of their tumors after treatment.

The treatment showed high efficacy with a 1-year overall survival rate of 100% and a progression-free survival rate of 83%, although it was associated with notable chemotherapy-related toxicities, including neutropenia and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. Hosein, PJ., Macintyre, J., Kawamura, C., 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]

In a comparison of two chemotherapy regimens for metastatic pancreatic cancer, FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GN), both treatments showed equivalent overall survival of 11.1 months and similar progression-free survival rates, indicating comparable efficacy.

However, the safety profiles differed: GN was associated with more frequent grade 3/4 anemia, while FFX led to higher rates of grade 3/4 vomiting and diarrhea, suggesting that while both treatments are effective, their side effects vary significantly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Equivalent Efficacy but Different Safety Profiles of Gemcitabine Plus Nab-Paclitaxel and FOLFIRINOX in Metastatic Pancreatic Cancer. Rapposelli, IG., Casadei-Gardini, A., Vivaldi, C., et al.[2022]

In a phase II trial involving 48 patients with gemcitabine-refractory unresectable pancreatic cancer, modified FOLFIRINOX demonstrated promising efficacy with an objective response rate of 18.8% and a disease control rate of 62.5%.

The treatment was associated with manageable safety concerns, primarily neutropenia (64.6% of patients), but most non-hematologic adverse events were mild, indicating that while effective, careful monitoring for hematologic toxicities is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase II trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer. Chung, MJ., Kang, H., Kim, HG., et al.[2020]

The modified FOLFIRINOX regimen is effective and well-tolerated for patients with advanced nonmetastatic pancreatic cancer, showing a high rate of surgical resection (72% attempted, 51.1% accomplished) with manageable toxicity, primarily diarrhea in 14% of patients.

Patients who underwent surgical resection after treatment with mFOLFIRINOX experienced a median progression-free survival of 18 months, significantly longer than the 8 months for those who did not have surgery, indicating a potential survival benefit from this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas. Blazer, M., Wu, C., Goldberg, RM., et al.[2022]

In a meta-analysis of eight studies, Folfirinox demonstrated higher rates of surgical resection and R0 resection, as well as improved progression-free survival (PFS) and overall survival (OS) compared to gemcitabine plus nab-paclitaxel (GNP) for patients with borderline resectable or locally advanced pancreatic cancer.

Importantly, Folfirinox did not lead to an increase in severe toxicity rates compared to GNP, suggesting it is a safer option while providing better efficacy in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of neoadjuvant Folfirinox and Gemcitabine plus Nab-Paclitaxel for borderline resectable and locally advanced pancreatic cancer: a systematic review and meta-analysis. Dong, LP., Liu, YM., Lu, WJ., et al.[2022]

In a study of 54 patients with advanced pancreatic cancer, S-IROX showed a higher disease control rate (73.7%) compared to modified FOLFIRINOX (mFFX) (62.2%), indicating it may be more effective as a second-line treatment after gemcitabine plus nab-paclitaxel.

Both S-IROX and mFFX had similar overall survival rates (14.2 months for S-IROX and 11.5 months for mFFX) and tolerability, with no significant differences in severe side effects, suggesting both regimens are viable options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective comparative study of S-IROX and modified FOLFIRINOX for patients with advanced pancreatic cancer refractory to gemcitabine plus nab-paclitaxel. Saito, K., Nakai, Y., Takahara, N., et al.[2022]

In a meta-analysis of 16 studies involving 3813 patients with metastatic pancreatic cancer, both GEM-NAB and FOLFIRINOX showed similar overall survival rates, despite FOLFIRINOX having a numerically longer median overall survival.

GEM-NAB was associated with lower rates of nausea and severe neutropenia compared to FOLFIRINOX, while FOLFIRINOX had lower rates of neurotoxicity and anemia, indicating that the choice between these treatments may depend on the patient's tolerance to side effects rather than a clear efficacy advantage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Gemcitabine plus Nab-Paclitaxel and FOLFIRINOX in the First-Line Setting of Metastatic Pancreatic Cancer: A Systematic Review and Meta-Analysis. Pusceddu, S., Ghidini, M., Torchio, M., et al.[2020]

Modified FOLFIRINOX (mFOLFIRINOX) is the most effective chemotherapy regimen for patients with pancreatic cancer in the adjuvant setting, showing a 98.9% probability of improving disease-free survival (DFS) and 89.6% for overall survival (OS).

Gemcitabine plus nab-paclitaxel (GEM-NAB) is a strong alternative to mFOLFIRINOX, with a higher likelihood of being the second most effective regimen compared to gemcitabine plus capecitabine (GEM-CAP), although both can be considered for patients unable to tolerate mFOLFIRINOX.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of modified FOLFIRINOX, gemcitabine plus capecitabine and gemcitabine plus nab-paclitaxel as adjuvant treatment for resected pancreatic cancer: a Bayesian network meta-analysis. de Jesus, VHF., Riechelmann, RP.[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]

Citations

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Modified FOLFIRINOX vs Gemcitabine/Nab-Paclitaxel in ... In the ITT population, median overall survival was 8.5 months in the mFOLFIRINOX group vs 9.7 months in the gemcitabine/nab-paclitaxel group (HR ...

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FOLFIRINOX vs Gemcitabine Plus Nab-Paclitaxel for ... Using cross-institutional clinical analysis, we found that treatment with FOLFIRINOX was associated with more than 2 months of survival ...