Neoadjuvant Therapy for Pancreatic Cancer

Not currently recruiting at 1 trial location

Overseen By Davendra Sohal, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Cincinnati

Must not be taking: Investigational agents

Disqualifiers: Uncontrolled illness, Pregnant, Breastfeeding, others

Stay on Your Current Meds You can continue your current medications while participating

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a treatment given before surgery can facilitate the removal of pancreatic cancer. The study tests two chemotherapy options, Folfirinox and Gemcitabine, to determine if they shrink tumors for more effective surgery. Suitable participants have been diagnosed with pancreatic cancer and have not yet begun any treatment. As a Phase 2 trial, the research focuses on measuring 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 if you need to stop taking your current medications. It is best to discuss this with the trial team or your doctor.

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

Research has shown that Folfirinox, a combination of chemotherapy drugs, is generally well-tolerated by people with pancreatic cancer. Studies indicate that it does not introduce any new safety issues when combined with other medications. However, some patients may experience side effects such as tiredness or low blood cell counts.

Gemcitabine, another chemotherapy drug for pancreatic cancer, is considered safe. Its side effects can include flu-like symptoms and low blood counts, but these are usually manageable.

Both treatments have established safety records in cancer care. While side effects can occur, they are often expected and are closely monitored by doctors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Folfirinox and Gemcitabine as neoadjuvant therapies for pancreatic cancer because these treatments are administered before surgery to potentially shrink tumors, making surgical removal more effective. Unlike the standard treatment options, which often start with surgery followed by chemotherapy, neoadjuvant therapy might enhance surgical outcomes and improve survival rates. Additionally, Folfirinox is known for its potent combination of chemotherapy drugs that work together to aggressively target cancer cells, while Gemcitabine is recognized for its ability to inhibit DNA replication, slowing tumor growth. By using these treatments upfront, there is hope for better managing the disease and enhancing patients' quality of life.

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

Research has shown that Folfirinox, included in this trial's neoadjuvant therapy, works well for some pancreatic cancer patients. Studies indicate it can extend survival for those whose cancer can be surgically removed. Comparisons with other treatments have found it safe and effective in certain situations.

For Gemcitabine, also part of the neoadjuvant therapy in this trial, evidence suggests it can prolong life. Patients receiving Gemcitabine after surgery have experienced better long-term outcomes. It is used before surgery to shrink tumors, making the procedure easier and more successful. Both treatments have shown promising results in improving surgical success for pancreatic cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Davendra P. Sohal

Principal Investigator

University of Cincinnati

Are You a Good Fit for This Trial?

This trial is for adults with confirmed pancreatic carcinoma or adenocarcinoma who haven't had prior treatment for it. They must be in good health otherwise, not have other serious illnesses that could affect the study, and agree to use contraception. People with controlled HIV or cured hepatitis are eligible, but pregnant women and those unable to follow the study plan can't join.

Inclusion Criteria

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

I am fully active and can carry on all my pre-disease activities without restriction.

I had cancer before, but it was treated over 2 years ago and won't affect this study.

Exclusion Criteria

You are not currently taking any other experimental medications. If you have taken experimental medications in the past but are not currently taking them, the decision to include you will be made by the Principal Investigator.

Pregnant women or women who are breastfeeding are excluded from this study.

I do not have any health conditions that would stop me from receiving standard cancer treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive FOLFIRINOX regimen, with potential switch to gemcitabine and nab-paclitaxel based on interim assessment

16 months

Regular visits for chemotherapy administration and assessment

Radiation Therapy

Radiation therapy may be used prior to surgery based on pre-operative scan findings

As needed prior to surgery

Surgical Resection

Participants undergo surgical resection if deemed resectable after neoadjuvant therapy

Surgery scheduled post-therapy

Follow-up

Participants are monitored for safety, effectiveness, and survival after treatment

5 years

Regular follow-up visits for monitoring

What Are the Treatments Tested in This Trial?

Interventions

• Folfirinox
• Gemcitabine
• Pancreatectomy
• Radiation Therapy

Trial Overview

The trial tests if neoadjuvant therapy (treatment given before main treatment) increases the chance of successfully removing pancreatic tumors through surgery. It involves a combination of chemotherapy drugs like Gemcitabine and Folfirinox, along with radiation therapy before a pancreatectomy.

How Is the Trial Designed?

Group I: Neoadjuvant therapy Experimental Treatment 4 Interventions

All patients will receive Neoadjuvant therapy.

Folfirinox is already approved in United States, European Union for the following indications:

Approved in United States as FOLFIRINOX for:

• Pancreatic cancer

Approved in European Union as FOLFIRINOX for:

• Pancreatic cancer

Who Is Running the Clinical Trial?

University of Cincinnati

Lead Sponsor

Trials

442

Recruited

639,000+

Published Research Related to This Trial

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 study of 25 patients with borderline resectable or locally unresectable pancreatic cancer, FOLFIRINOX treatment led to a 33% R0 resection rate, indicating successful surgical removal of tumors after neoadjuvant therapy.

The regimen showed promising biological activity, with 24% of patients achieving significant pathologic responses, suggesting that FOLFIRINOX could be an effective neoadjuvant treatment option for this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes with FOLFIRINOX for borderline resectable and locally unresectable pancreatic cancer. Boone, BA., Steve, J., Krasinskas, AM., et al.[2022]

In a study of 342 patients with metastatic pancreatic cancer, the FOLFIRINOX chemotherapy regimen significantly improved overall survival (11.1 months) compared to gemcitabine (6.8 months), indicating it is a more effective first-line treatment option.

While FOLFIRINOX showed a higher objective response rate (31.6% vs. 9.4% for gemcitabine), it also resulted in more adverse events, including a 5.4% incidence of febrile neutropenia, highlighting the need to balance efficacy with safety in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. Conroy, T., Desseigne, F., Ychou, M., et al.[2023]

Patients with metastatic pancreatic cancer treated with Folfirinox (FFX) had a significantly longer overall survival (14 months) compared to those treated with gemcitabine/nab-paclitaxel (GN) (9 months), indicating that FFX may be a more effective first-line treatment.

The study suggests that using FFX followed by GN after FFX failure is more feasible, with a higher proportion of patients able to receive GN after FFX treatment, leading to a median overall survival of 19 months compared to 9.5 months for the reverse sequence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Folfirinox versus gemcitabine/nab-paclitaxel as first-line therapy in patients with metastatic pancreatic cancer: a comparative propensity score study. Williet, N., Saint, A., Pointet, AL., et al.[2022]

The introduction of FOLFIRINOX and gemcitabine plus nab-paclitaxel therapy significantly improved treatment outcomes for metastatic pancreatic cancer, with response rates increasing from 7.8% to 28.4% after these therapies were introduced.

Patients treated with the newer therapies experienced longer median progression-free survival (3.1 months to 5.4 months) and median overall survival (6.7 months to 10.2 months), indicating a substantial benefit in daily clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement of Treatment Outcomes for Metastatic Pancreatic Cancer: A Real-world Data Analysis. Sasaki, T., Kanata, R., Yamada, I., 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 92 patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (PDAC) treated with FOLFIRINOX and radiation, 16% achieved a complete pathological response, indicating the treatment's effectiveness in the neoadjuvant setting.

The study identified a tumour-to-tumour bed ratio of 11.6% as a significant predictor of overall survival, suggesting that this quantitative measure may be more reliable than traditional pathology parameters for assessing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreatic ductal adenocarcinoma: tumour regression grading following neoadjuvant FOLFIRINOX and radiation. Neyaz, A., Tabb, ES., Shih, A., et al.[2023]

In a study of 18 patients with metastatic pancreatic cancer, the maximum tolerated dose (MTD) for second-line chemotherapy using FOLFIRINOX was determined to be 100 mg/m² of irinotecan, with a response rate of 22.2% and a disease control rate of 61.1%.

The most common severe side effect was neutropenia, affecting 66.7% of patients, indicating that while FOLFIRINOX can be marginally effective after gemcitabine failure, it carries significant risks of toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of FOLFIRINOX as second-line chemotherapy for metastatic pancreatic cancer after gemcitabine-based chemotherapy failure. Kobayashi, N., Shimamura, T., Tokuhisa, M., et al.[2022]

In a study involving 342 patients with metastatic pancreatic adenocarcinoma, FOLFIRINOX demonstrated a significantly better overall survival compared to gemcitabine, with a net chance of a better outcome of 24.7 (P<.001).

The analysis indicated that FOLFIRINOX has a favorable benefit-risk balance, meaning that the survival benefits outweigh the associated toxicities when compared to gemcitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An assessment of the benefit-risk balance of FOLFIRINOX in metastatic pancreatic adenocarcinoma. Péron, J., Roy, P., Conroy, T., et al.[2022]

In a study of 83 patients with metastatic pancreatic ductal adenocarcinoma, the FOLFIRINOX (FFX) regimen showed the best progression-free survival (PFS) of 9 months compared to 5 months for both gemcitabine-based regimens (GB) and gemcitabine monotherapy (Gem).

Overall survival (OS) was also highest for the FFX group at 14 months, indicating that FFX may be the most effective first-line treatment option for this condition, with male gender, ECOG performance status, and elevated neutrophil-to-lymphocyte ratio identified as independent predictors of survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Life Results of Palliative Chemotherapy in Metastatic Pancreatic Ductal Adenocarcinoma. Varzaru, B., Iacob, RA., Croitoru, AE., 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]

In a study of 274 pancreatic ductal adenocarcinoma (PDAC) patients, those who showed a significant biochemical response (CA 19-9 decrease ≥50%) after neoadjuvant chemotherapy had better overall survival (OS) and recurrence-free survival compared to those with less response, indicating the importance of monitoring this biomarker.

The study found no significant difference in survival outcomes between patients treated with the two chemotherapy regimens, FOLFIRINOX (FLX) and gemcitabine/nab-paclitaxel (GNP), suggesting that both are equally effective in improving survival rates in PDAC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival Outcomes Associated With Clinical and Pathological Response Following Neoadjuvant FOLFIRINOX or Gemcitabine/Nab-Paclitaxel Chemotherapy in Resected Pancreatic Cancer. Macedo, FI., Ryon, E., Maithel, SK., et al.[2022]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6695305/

Neoadjuvant FOLFIRINOX in Patients With Borderline ...

FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline ...

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S2468294224000169

Neoadjuvant treatment for pancreatic cancer

This review analyzes the evidence regarding controversial topics in neoadjuvant pancreatic cancer treatment and discusses further research efforts to enhance ...

3.

jamanetwork.com

jamanetwork.com/journals/jamaoncology/fullarticle/2820217

Perioperative Modified FOLFIRINOX for Resectable ...

In this study, perioperative modified FOLFIRINOX was safe and effective, with a clinically meaningful improvement in survival compared with historical controls.

4.

thelancet.com

thelancet.com/journals/langas/article/PIIS2468-1253(23)00405-3/abstract

Neoadjuvant FOLFIRINOX versus upfront surgery for ...

This phase 2 trial did not show a survival benefit from neoadjuvant FOLFIRINOX in resectable pancreatic ductal adenocarcinoma compared with ...

5.

ascopubs.org

ascopubs.org/doi/pdf/10.1200/JCO-24-01378

Neoadjuvant FOLF(IRIN)OX Chemotherapy for Resectable

PURPOSE Despite limited RCTs, neoadjuvant chemotherapy (NAC) shows promise for re- sectable pancreatic adenocarcinoma (rPAC). Few prospective ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7081111/

FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in ...

Pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis, with a 5-year overall survival (OS) rate of only 8%-9% for all stages taken ...

7.

ascopubs.org

ascopubs.org/doi/10.1200/jco.2013.31.15_suppl.e15176

Safety and efficacy of modified dose-attenuated ...

Safety and efficacy of modified dose-attenuated FOLFIRINOX chemotherapy in patients over 65 years with advanced pancreatic adenocarcinoma.

8.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1011923

FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic ...

Data are lacking on the efficacy and safety of a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin ...

9.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01383538

Study Details | NCT01383538 | FOLFIRINOX Plus IPI-926 ...

Recent evidence in a genetically engineered mouse model of pancreatic cancer demonstrated that IPI-926 can deplete tumor-associated stromal tissue and increase ...

10.

onclive.com

onclive.com/view/pelareorep-plus-mfolfirinox-atezolizumab-shows-acceptable-safety-in-metastatic-pdac

Pelareorep Plus mFOLFIRINOX ± Atezolizumab Shows ...

Pelareorep with mFOLFIRINOX, with/without atezolizumab, showed acceptable safety in metastatic PDAC patients, with no new safety signals ...