Chemotherapy + Immunotherapy for Pancreatic Cancer

Recruiting at 2 trial locations

Overseen By Benjamin Musher

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Baylor College of Medicine

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: HIV, Cardiovascular disease, Autoimmune, 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

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a combination of chemotherapy and immunotherapy for treating surgically removable pancreatic cancer. The treatment involves using FOLFIRINOX (a mix of cancer-fighting drugs) and Pembrolizumab (an immune booster) before and after surgery. It targets patients with pancreatic cancer that hasn't spread and is confirmed as removable by a doctor. Participants should not have received previous treatments like chemotherapy or radiation for their pancreatic cancer. 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 protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or have received certain treatments like live vaccines recently, you may need to adjust your medications. It's best to discuss your specific situation with the trial team.

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

Previous studies have used FOLFIRINOX to treat pancreatic cancer. It has shown effectiveness but 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 with medical assistance.

Pembrolizumab, an immunotherapy, is already approved for conditions like melanoma. Although researchers are still studying it for pancreatic cancer, early safety data suggest it is generally well-tolerated. Some individuals might experience side effects like tiredness or skin reactions, which are common with this type of treatment.

The trial under consideration combines both treatments. While each has its side effects, they have been used in other settings, and medical teams know how to manage these reactions. Participants will be closely monitored to ensure safety. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for pancreatic cancer?

Researchers are excited about combining Folfirinox with Pembrolizumab for pancreatic cancer because it represents a novel approach by integrating chemotherapy with immunotherapy. Folfirinox, a powerful chemotherapy regimen, is already known for its effectiveness against pancreatic cancer, but when paired with Pembrolizumab, an immune checkpoint inhibitor, it may enhance the body's immune response to attack cancer cells more effectively. Unlike conventional treatments that rely solely on chemotherapy, this combination aims to boost the immune system's ability to recognize and fight cancer, potentially leading to better outcomes. This dual approach could offer new hope for patients by possibly improving survival rates and reducing recurrence compared to standard chemotherapy alone.

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

Studies have shown that FOLFIRINOX can effectively treat pancreatic cancer. One study found that patients receiving FOLFIRINOX lived a median of 11.1 months, compared to 6.8 months for those treated with gemcitabine. Tumor shrinkage or disappearance occurred at a higher rate with FOLFIRINOX, at 47.8%.

In this trial, participants will receive a combination of FOLFIRINOX and pembrolizumab. Although pembrolizumab, an immunotherapy drug, has shown mixed results when used alone, combining it with FOLFIRINOX could be promising, particularly for patients who might benefit from the added immunotherapy. ^{2 5 6 7 8}

Who Is on the Research Team?

Ernest R. Camp, M.D., M.S.C.R., F.A.C.S.

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for adults with a specific type of pancreatic cancer that can potentially be removed by surgery. They should not have had previous chemotherapy or radiation, must be in good physical condition (ECOG PS 0-1), and have normal organ function. Women of childbearing age must test negative for pregnancy and agree to use contraception.

Inclusion Criteria

My liver is functioning properly.

My main abdominal veins are open and not blocked.

- Absolute neutrophil count (ANC) ≥1500/μL

Exclusion Criteria

I have been treated with specific immune therapy drugs before.

I am not on high-dose steroids or other drugs that weaken my immune system.

I have a history of Hepatitis B or active Hepatitis C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive 6 cycles of FOLFIRINOX and 2 cycles of Pembrolizumab before surgical resection

12 weeks

Surgery

Surgical resection of the pancreatic tumor

1 week

Adjuvant Chemotherapy

Participants receive 5-Fluorouracil based chemotherapy for up to 6 cycles with 7 more cycles of Pembrolizumab

54 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Folfirinox
• Pembrolizumab

Trial Overview The study is testing the combination of Folfirinox (a mix of chemotherapy drugs) with Pembrolizumab, an immunotherapy drug, given before surgery to remove the cancer. This Phase II trial will compare results against past data from similar patients who didn't receive this combo treatment.

How Is the Trial Designed?

Group I: Neoadjuvant Folfirinox and Pembrolizumab followed by sx for patients with pancreatic cancer Experimental Treatment 2 Interventions

Patients will receive 6 cycles of Folfirinox (Oxaliplatin 85 mg/m2, Leucovorin 400 mg/m2, Irinotecan 150 mg/m2, 5-Fluorouracil 2,400 mg/m2) with 2 cycles of Pembrolizumab 400 mg before surgical resection. Following surgery patients will receive 5-Fluorouracil based chemotherapy for up to 6 cycles with 7 more cycles of Pembrolizumab. Patients will receive a total of 9 doses of Q6week cycles of Pembrolizumab.

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?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a study of 243 patients with advanced pancreatic adenocarcinoma treated with FOLFIRINOX, the relative dose intensity (RDI) of the treatment agents did not significantly correlate with disease control or objective response, suggesting that dose reductions may not compromise treatment effectiveness.

The median cumulative multi-drug RDI was 80%, and including RDI in predictive models did not enhance the ability to forecast disease control, indicating that oncologists can safely adjust doses without fearing a loss of therapeutic benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX relative dose intensity and disease control in advanced pancreatic adenocarcinoma. Vary, A., Lebellec, L., Di Fiore, F., et al.[2022]

The combination of panitumumab and bevacizumab with FOLFIRI chemotherapy significantly improved treatment outcomes for patients with metastatic colorectal cancer, showing a response rate of 40.1% compared to 30.1% for FOLFIRI alone.

Patients receiving the FOLFIRI+PB combination had a median overall survival of 13.9 months, which is longer than the 10.7 months observed in the FOLFIRI-only group, indicating enhanced efficacy of the combined treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of second-line treatment with folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) in combination of panitumumab and bevacizumab for patients with metastatic colorectal cancer. Xie, S., Han, G., Fan, Z., et al.[2021]

FOLFIRINOX (FFX) has been shown to significantly improve median overall survival, progression-free survival, and objective response rates in patients with metastatic pancreatic cancer compared to gemcitabine, as established in the PRODIGE 4/ACCORD 11 study.

Despite initial concerns about its toxicity, FFX has been widely adopted in clinical practice, leading to new research opportunities and discussions about managing its side effects and optimizing treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreatic cancer and FOLFIRINOX: a new era and new questions. Marsh, Rde W., Talamonti, MS., Katz, MH., et al.[2023]

FOLFIRINOX, a combination chemotherapy regimen, has been shown to significantly improve overall survival and progression-free survival in patients with metastatic pancreatic cancer compared to the traditional treatment with gemcitabine, based on results from the PRODIGE 4/ACCORD 11 trial.

While FOLFIRINOX is associated with higher toxicity rates, including febrile neutropenia and diarrhea, its rapid adoption in clinical practice highlights its effectiveness, and further studies are needed to explore its benefits in other treatment settings like second-line therapy and adjuvant chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status on the place of FOLFIRINOX in metastatic pancreatic cancer and future directions. Lambert, A., Gavoille, C., Conroy, T.[2021]

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]

The sequential treatment of nab-paclitaxel/gemcitabine followed by FOLFIRINOX in metastatic pancreatic cancer showed a high objective response rate of 64.9% and acceptable toxicity, with no deaths reported during the study.

Patients experienced manageable side effects, primarily neutropenia and venous thromboembolism, while achieving a median progression-free survival of 10.5 months and overall survival of 15.1 months, indicating the treatment's potential effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential first-line treatment with nab-paclitaxel/gemcitabine and FOLFIRINOX in metastatic pancreatic adenocarcinoma: GABRINOX phase Ib-II controlled clinical trial. Assenat, E., de la Fouchardière, C., Portales, F., 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 study of 1102 patients with metastatic pancreatic cancer, FOLFIRINOX treatment resulted in a median overall survival of 9.27 months, significantly longer than the 6.87 months observed with gemcitabine plus nab-paclitaxel (P < 0.001).

Patients receiving FOLFIRINOX also experienced 17.3% fewer posttreatment hospitalizations and 20% lower posttreatment costs compared to those treated with gemcitabine plus nab-paclitaxel, indicating better safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of FOLFIRINOX vs Gemcitabine Plus Nab-Paclitaxel as First-Line Chemotherapy for Metastatic Pancreatic Ductal Adenocarcinoma. Klein-Brill, A., Amar-Farkash, S., Lawrence, G., et al.[2023]

In a study of 100 patients with metastatic pancreatic cancer, only 26% met the eligibility criteria for FOLFIRINOX treatment, highlighting the challenges in patient selection for this therapy.

The most common reasons for exclusion from FOLFIRINOX were poor performance status, older age, elevated bilirubin levels, and inadequate renal function, indicating a need for more tolerable treatment options for the majority of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Defining Eligibility of FOLFIRINOX for First-Line Metastatic Pancreatic Adenocarcinoma (MPC) in the Province of British Columbia: A Population-based Retrospective Study. Ho, MY., Kennecke, HF., Renouf, DJ., et al.[2018]

In a pilot study of 20 patients with advanced pancreatic ductal adenocarcinoma (PDAC), chemotherapy with FOLFIRINOX or gemcitabine/nab-paclitaxel led to heterogeneous changes in circulating T-cell populations, particularly affecting PD-1+ CD4+/CD8+ T cells.

An increase in TIM-3+/CD8+ T cells was linked to significantly worse clinical outcomes, with median progression-free survival of 6 months compared to 14 months for those with stable or decreased levels, suggesting that monitoring these immune changes could provide important prognostic information.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alterations in regulatory T cells and immune checkpoint molecules in pancreatic cancer patients receiving FOLFIRINOX or gemcitabine plus nab-paclitaxel. Sams, L., Kruger, S., Heinemann, V., et al.[2022]

In a study of 41 pancreas cancer patients treated with pembrolizumab, the median overall survival was 7.2 months, which is considered favorable compared to the benchmark of over 4 months.

Patients with specific genetic markers (dMMR, MSI-H, TMB-H, or Lynch syndrome) had a significantly lower risk of death, indicating that these biomarkers may help identify patients who could benefit more from pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab near the end of life in patients with metastatic pancreatic cancer: a multi-site consecutive series to examine survival and patient treatment burden. Storandt, MH., Tran, N., Martin, N., 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]

Citations

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

FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in ... Detailed outcomes data are summarized in Table 2. The objective response rate was 47.8% in the FOLFIRINOX group, compared to 37.1% in the ...

2. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2795978

Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as ... This randomized clinical trial examines 5-year outcomes and prognostic factors for overall survival for treatment with modified FOLFIRINOX ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1011923

FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic ... Results. The median overall survival was 11.1 months in the FOLFIRINOX group as compared with 6.8 months in the gemcitabine group (hazard ratio for death, 0.57; ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3816713/

Outcomes with FOLFIRINOX for Borderline Resectable and ... A randomized trial of FOLFIRINOX versus gemcitabine in metastatic pancreatic cancer showed improved median survival from 6.8 to 11.1 months[25]. Further studies ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)33892-X/fulltext

Effectiveness and costs of FOLFIRINOX in the treatment ... Median overall survival was 9,87 months (CI 95%: 8,378- 11,362 months). Time till progression was 6.41 months (range: 0,67- 20,27 months). The rate of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9087258/

Efficacy and safety of FOLFIRINOX as second-line ... FOLFIRINOX is recommended as a second-line chemotherapy regimen for patients with pancreatic cancer that have failed on gemcitabine-based first-line therapy.

7. ascopubs.org ascopubs.org/doi/10.1200/jco.2012.30.15_suppl.e14614

Safety and efficacy of modified FOLFIRINOX in pancreatic ... We present our experience with mFOLFIRINOX in patients with locally advanced or metastatic pancreatic cancer. Methods: After obtaining IRB ...

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)46893-2/fulltext

Safety and efficacy of modified FOLFIRINOX in patients ... Background: FOLFIRINOX (FFX) has been regarded as one of the standard treatments for patients with metastatic pancreatic cancer (MPC).