What side effects are associated with this type of intervention?

Common treatments for pancreatic cancer, such as FOLFIRINOX and Pembrolizumab, have notable side effects. FOLFIRINOX can cause neutropenia, fatigue, diarrhea, and neuropathy. Pembrolizumab, an immune checkpoint inhibitor, may lead to immune-related adverse effects like pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. Combining these treatments could increase the risk of both chemotherapy-related and immune-related side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for pancreatic cancer, including combination chemotherapy regimens like FOLFIRINOX, which consists of leucovorin, fluorouracil, oxaliplatin, and irinotecan. This regimen is often used for patients with advanced pancreatic cancer due to its efficacy in improving survival rates. Additionally, immune checkpoint inhibitors like Pembrolizumab have been explored in various cancers, including pancreatic cancer, although their use in this specific context is still under investigation. The combination of chemotherapy and immune checkpoint inhibition, as studied in the trial involving Neoadjuvant FOLFIRINOX combined with Pembrolizumab, represents a promising area of research aimed at enhancing treatment efficacy for resectable pancreatic cancer.

What other types of research exist?

Promising novel alternatives to Neoadjuvant FOLFIRINOX combined with Pembrolizumab for pancreatic cancer patients include: 1) Aflibercept plus FOLFIRI, which has shown significant improvements in overall survival and progression-free survival in metastatic colorectal cancer and may be explored for pancreatic cancer. 2) Combinations of immune checkpoint inhibitors such as nivolumab or ipilimumab with chemotherapy or other targeted therapies. 3) Personalized treatment approaches based on genetic profiling and biomarkers to tailor therapy to individual patient characteristics. Patients should discuss these options with their oncologist to determine the most appropriate treatment plan.

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Chemotherapy

Chemotherapy + Immunotherapy for Pancreatic Cancer

Q: What is the mechanism of action of this treatment?

The FOLFIRINOX regimen combines four chemotherapy agents: folinic acid (leucovorin), fluorouracil (5-FU), irinotecan, and oxaliplatin. These agents work synergistically to inhibit DNA synthesis and repair, leading to cancer cell death. Folinic acid enhances the effectiveness of fluorouracil, which disrupts DNA and RNA synthesis. Irinotecan inhibits topoisomerase I, preventing DNA unwinding necessary for replication, while oxaliplatin forms cross-links in DNA, obstructing replication and transcription. Pembrolizumab, an immune checkpoint inhibitor, targets the PD-1 receptor on T-cells, preventing cancer cells from evading immune detection. This combination is significant for pancreatic cancer patients as it not only directly attacks cancer cells but also enhances the immune system's ability to recognize and destroy them, potentially improving outcomes in a cancer type known for its poor prognosis.

Phase 2

Recruiting

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

Research Sponsored by Baylor College of Medicine

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

- No extension to superior mesenteric artery (SMA) and hepatic artery. Patent superior mesenteric vein/portal vein (SMV/PV) with < 180-degree abutment and no evidence of invasion.

Patient must not have received prior chemotherapy or radiation for pancreatic cancer.

Must not have

Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).

Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of chemotherapy and immune therapy for patients with a specific type of pancreatic cancer. The goal is to improve surgery outcomes by shrinking the tumor and boosting the body's ability to fight cancer.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include reactions related to the immune system attacking normal organs, infusion-related reactions from the drug entering your body, fatigue, nausea or vomiting due to chemo drugs, blood cell count changes increasing infection risk.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer has not spread to major arteries or veins near my liver.

Select...

I have not had chemotherapy or radiation for pancreatic cancer.

Select...

My liver is functioning properly.

Select...

My main abdominal veins are open and not blocked.

Select...

My kidney function is within the required range.

Select...

I am over 18 and have a type of pancreatic cancer that can potentially be surgically removed.

Select...

I am fully active or restricted in physically strenuous activity but can do light work.

Select...

My kidney function, measured by creatinine or GFR, is within the required range.

Select...

My cancer has not spread to the celiac axis or hepatic artery.

Select...

My cancer has not spread to distant parts of my body.

Select...

I agree to follow the study's rules for using contraception and not donate sperm for a specified time after the last dose.

Select...

I am a male.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have been treated with specific immune therapy drugs before.

Select...

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

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I experience significant numbness, pain, or weakness in my hands or feet.

Select...

I have or had lung inflammation not caused by infection, treated with steroids.

Select...

I have received an organ or tissue transplant from another person.

Select...

I do not have any active infections needing treatment.

Select...

My cancer is advanced but hasn't spread widely and isn't one of the excluded types.

Select...

I am HIV positive.

Select...

I am willing and able to follow the study's procedures.

Select...

I am allergic to the medication used in this study.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Determine if the neoadjuvant FOLFIRINOX chemotherapy followed by pembrolizumab followed by surgery will improve the overall response rate (ORR) for patients with localized, resectable adenocarcinoma of the pancreas.

Secondary study objectives

Determine if the addition of pembrolizumab to neoadjuvant mFOLFIRINOX leads to improved CD8+ T cell frequencies in resected tumor samples in comparison to archived matched controls from patients meeting the same I/E criteria as those in the study.

Estimate the effect of combination neoadjuvant therapy on the R0 resection rate

Estimate the effect of combined neoadjuvant therapy on relapse-free survival, time to recurrence and overall survival.

+1 more

Side effects data

From 2024 Phase 3 trial • 804 Patients • NCT03040999

64%

Radiation skin injury

63%

Stomatitis

58%

Anaemia

56%

Nausea

48%

Dry mouth

45%

Constipation

45%

Weight decreased

44%

Dysphagia

42%

Neutrophil count decreased

33%

Dysgeusia

33%

Vomiting

32%

Fatigue

31%

White blood cell count decreased

28%

Hypomagnesaemia

26%

Decreased appetite

25%

Hypothyroidism

25%

Hypokalaemia

24%

Lymphocyte count decreased

24%

Platelet count decreased

23%

Oropharyngeal pain

23%

Blood creatinine increased

22%

Diarrhoea

22%

Odynophagia

20%

Hypoacusis

20%

Alanine aminotransferase increased

20%

Hyponatraemia

19%

Tinnitus

19%

Oral candidiasis

19%

Asthenia

16%

Pyrexia

16%

Cough

15%

Aspartate aminotransferase increased

15%

Rash

14%

Insomnia

13%

Acute kidney injury

13%

Pharyngeal inflammation

13%

Pruritus

12%

Dysphonia

12%

Gamma-glutamyltransferase increased

11%

Pneumonia

11%

Dehydration

10%

Hyperthyroidism

10%

Hypoalbuminaemia

10%

Hypocalcaemia

10%

Headache

10%

Productive cough

Neck pain

Peripheral sensory neuropathy

Gastrooesophageal reflux disease

Hiccups

Hyperglycaemia

Hyperuricaemia

Dizziness

Hypophosphataemia

Urinary tract infection

Ear pain

Localised oedema

Hyperkalaemia

Erythema

Oral pain

Abdominal pain upper

Arthralgia

Anxiety

Febrile neutropenia

Dyspepsia

Saliva altered

Back pain

Oedema peripheral

Hypertension

Dyspnoea

Nasopharyngitis

Alopecia

Dry skin

Sepsis

Pneumonia aspiration

Trismus

Pneumonitis

Laryngeal oedema

Malnutrition

Pharyngeal haemorrhage

Cellulitis

Septic shock

Systemic infection

Clostridium difficile colitis

Cardiac arrest

Death

Bronchitis

Hepatitis

Immune-mediated hepatitis

Oesophagitis

General physical health deterioration

Hypophagia

Tumour haemorrhage

Cerebrovascular accident

Syncope

Acute respiratory failure

Aspiration

Colitis

Mouth haemorrhage

Hypersensitivity

Acute myocardial infarction

Abscess neck

Device related infection

Stoma site infection

Vascular device infection

Wound infection

Hypercalcaemia

Pulmonary embolism

Respiratory failure

100%

80%

60%

40%

20%

Study treatment Arm

Pembrolizumab + CRT Followed by Pembrolizumab

Placebo + CRT Followed by Placebo

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Neoadjuvant Folfirinox and Pembrolizumab followed by sx for patients with pancreatic cancerExperimental Treatment2 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~3150

Folfirinox

2018

Completed Phase 3

~760

0 / 22Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The FOLFIRINOX regimen combines four chemotherapy agents: folinic acid (leucovorin), fluorouracil (5-FU), irinotecan, and oxaliplatin. These agents work synergistically to inhibit DNA synthesis and repair, leading to cancer cell death. Folinic acid enhances the effectiveness of fluorouracil, which disrupts DNA and RNA synthesis. Irinotecan inhibits topoisomerase I, preventing DNA unwinding necessary for replication, while oxaliplatin forms cross-links in DNA, obstructing replication and transcription. Pembrolizumab, an immune checkpoint inhibitor, targets the PD-1 receptor on T-cells, preventing cancer cells from evading immune detection. This combination is significant for pancreatic cancer patients as it not only directly attacks cancer cells but also enhances the immune system's ability to recognize and destroy them, potentially improving outcomes in a cancer type known for its poor prognosis.

Promising new therapies in advanced pancreatic adenocarcinomas.