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

Trial Summary

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.

What data supports the effectiveness of the drug Gemcitabine, Gemzar, mFOLFIRINOX, modified FOLFIRINOX, mFOLFIRINOX, FOLFIRINOX, Nab paclitaxel, Abraxane for pancreatic cancer?

Research shows that both gemcitabine-nab-paclitaxel and FOLFIRINOX improve survival in patients with advanced pancreatic cancer compared to using gemcitabine alone. Modified FOLFIRINOX has also been effective as a second-line treatment for pancreatic cancer when other treatments like gemcitabine have failed. ^{1 2 3 4 5}

Is neoadjuvant chemotherapy for pancreatic cancer safe for humans?

Gemcitabine, nab-paclitaxel, and FOLFIRINOX are used in treating pancreatic cancer and have different safety profiles. Gemcitabine with nab-paclitaxel may cause more anemia, while FOLFIRINOX may lead to more vomiting and diarrhea. Both treatments are generally considered safe but have distinct side effects. ^{1 5 6 7 8}

How is the drug combination of Gemcitabine, mFOLFIRINOX, and Nab paclitaxel unique for treating pancreatic cancer?

This drug combination is unique because it uses a multi-agent approach, combining Gemcitabine, mFOLFIRINOX, and Nab paclitaxel, which has shown improved outcomes compared to single-agent treatments like Gemcitabine alone. The modified FOLFIRINOX regimen is particularly notable for its ability to potentially shrink tumors enough to make surgical removal possible, even in cases where the cancer was initially considered inoperable. ^{2 9 10 11 12}

What is the purpose of this trial?

The objective of this research is to find out what effects (good and bad), the sequence of Gemcitabine - Abraxane (nab-Paclitaxel) followed by mFOLFIRINOX, the standard chemotherapy for pancreatic cancer, has on participants and their condition. Gemcitabine - Abraxane (nab-Paclitaxel) and mFOLFIRINOX has been approved by the US Food and Drug Administration (FDA) as first line treatment for advanced pancreatic cancer. The sequence of Gemcitabine - Abraxane (nab-Paclitaxel) followed by mFOLFIRINOX has not been approved by the FDA for treatment of pancreatic cancer.

Research Team

Ravi K Paluri, MD

Principal Investigator

Wake Forest Baptist Comprehensive Cancer Center

Eligibility Criteria

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

Patients receiving any other investigational anti-neoplastic agents

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

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 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]

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]

References

1. United States 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. [2022]

2. Greece 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. [2022]

3. England 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. [2022]

4. 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]

5. China pubmed.ncbi.nlm.nih.gov

Multicenter phase II trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer. [2020]

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

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

7. Switzerland pubmed.ncbi.nlm.nih.gov

Equivalent Efficacy but Different Safety Profiles of Gemcitabine Plus Nab-Paclitaxel and FOLFIRINOX in Metastatic Pancreatic Cancer. [2022]

8. Switzerland 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. [2020]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Therapeutic drug monitoring of neoadjuvant mFOLFIRINOX in resected pancreatic ductal adenocarcinoma. [2023]

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

Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas. [2022]

11. England pubmed.ncbi.nlm.nih.gov

A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. [2022]

12. Italy 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. [2022]