Pembrolizumab + Chemotherapy for Pancreatic Cancer

Overseen By Katherine Vandris

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: Corticosteroids, Immunosuppressives, Probiotics, others

Disqualifiers: Autoimmune disease, Cardiovascular disease, HIV, 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: 6

Duration: 3 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of antibiotics and pembrolizumab, a type of immunotherapy, to evaluate their effectiveness after chemotherapy in treating surgically removable pancreatic cancer. The researchers aim to determine if this new approach can help patients better combat their cancer post-surgery. Individuals with confirmed pancreatic adenocarcinoma, who have not yet received treatment and are eligible for surgery, might be suitable candidates for this study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on medications for autoimmune diseases or require systemic treatment with corticosteroids, you may not be eligible to participate. It's best to discuss your specific medications with the trial team.

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

Research shows that pembrolizumab is generally well-tolerated. The FDA has already approved it for other uses, indicating its safety is well-understood. Studies have found that even in patients who have tried many other treatments, pembrolizumab's side effects are usually manageable and not severe.

Ciprofloxacin and metronidazole are antibiotics with well-known safety records. Ciprofloxacin might cause mild side effects like nausea or diarrhea. Metronidazole can also cause mild side effects, such as a metallic taste in the mouth or an upset stomach.

Overall, these treatments have been shown to be safe in other situations. However, discussing any concerns with the study team is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pembrolizumab with chemotherapy for pancreatic cancer because it introduces an innovative way to enhance the body's immune response against cancer. Unlike standard treatments, such as gemcitabine or FOLFIRINOX, which primarily target cancer cells directly, pembrolizumab is an immunotherapy that works by blocking the PD-1 pathway. This pathway can be used by cancer cells to hide from the immune system, so blocking it helps the immune system recognize and attack cancer more effectively. Additionally, the inclusion of antibiotics like ciprofloxacin and metronidazole may help manage infections and improve patient outcomes during treatment. This multi-faceted approach could potentially improve survival rates and offer new hope for patients with surgically resectable pancreatic cancer.

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

Research has shown that pembrolizumab, a type of immune therapy, could be promising for treating pancreatic cancer. In some patients with rare types of this cancer, the average time before the disease worsened was 12 months, and about 80% of these patients survived for at least one year. Another study found that patients treated with pembrolizumab lived for an average of over four months. While these results are hopeful, they can vary, and pembrolizumab might work better for some patients than others. Participants in this trial will receive pembrolizumab following chemotherapy, along with antibiotics, to evaluate its effectiveness in surgically resectable pancreatic cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Deirdre Cohen, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for adults over 18 with resectable pancreatic cancer who haven't had prior treatments. They must have normal organ function, no contact between the tumor and certain arteries or veins, and an ECOG performance status of 0 or 1. Participants need to consent to biopsies and surgery, use contraception if necessary, and not have autoimmune diseases, significant heart disease, recent major surgeries without recovery, active infections requiring treatment within the last month, HIV/Hepatitis A/B infection history or other conditions that would exclude them.

Inclusion Criteria

I agree to undergo initial, during-treatment, and final surgical biopsies.

My pancreatic cancer can be surgically removed.

My organ and bone marrow functions are normal.

Exclusion Criteria

I have HIV or active Hepatitis A or B.

I will not need cancer treatment or surgery other than the study.

My cancer is at a stage where surgery might not remove it all, or it has spread.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive chemotherapy with 5-Fluorouracil, Leucovorin, Irinotecan, and Oxaliplatin

8 weeks

5 visits (in-person)

Treatment

Participants receive antibiotics and pembrolizumab following chemotherapy

3 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ciprofloxacin
• Metronidazole
• Pembrolizumab

Trial Overview The study tests a combination of antibiotics (Metronidazole and Ciprofloxacin) with Pembrolizumab immunotherapy following FOLFIRINOX chemotherapy in patients with operable pancreatic cancer. It's a single-arm pilot study where all participants receive the same treatment sequence including surgical resection of their tumors.

How Is the Trial Designed?

Group I: Participants who had Chemotherapy Following Pancreatic Adenocarcinoma Experimental Treatment 6 Interventions

Participants to be given antibiotics and pembrolizumab, following chemotherapy for the treatment of surgically resectable pancreatic cancer.

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Published Research Related to This Trial

Ciprofloxacin demonstrated superior antibacterial activity compared to norfloxacin and nalidixic acid, being 2-8 times more effective than norfloxacin and 100 times more effective than nalidixic acid against a range of clinically important bacteria, based on tests with approximately 300 clinical isolates.

In mouse protection studies, ciprofloxacin was significantly more effective than other antibiotics like ampicillin and trimethoprim-sulfamethoxazole, showing rapid bactericidal action and excellent efficacy against Pseudomonas infections, with no observed cross-resistance to beta-lactam antibiotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The in vitro and in vivo activity of ciprofloxacin. Zeiler, HJ., Grohe, K.[2022]

In a study involving 671 patients with complicated intra-abdominal infections, ciprofloxacin/metronidazole (CIP/MTZ) showed similar effectiveness to imipenem/cilastatin (IMI) with overall success rates of 82% for CIP/MTZ IV and 82% for IMI IV.

Switching from intravenous to oral therapy with CIP/MTZ was highly effective, achieving a 96% success rate in patients who could tolerate oral feeding, indicating that oral therapy can be a viable option for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a randomized trial comparing sequential intravenous/oral treatment with ciprofloxacin plus metronidazole to imipenem/cilastatin for intra-abdominal infections. The Intra-Abdominal Infection Study Group. Solomkin, JS., Reinhart, HH., Dellinger, EP., et al.[2019]

Ciprofloxacin demonstrated significant anti-inflammatory effects in a mouse model of chemical colitis, reducing clinical signs and inflammation compared to saline and ceftazidime treatments.

The study found that ciprofloxacin not only lowered levels of pro-inflammatory cytokines like IL-1beta and TNFalpha but also showed less activation of NFkappaB, suggesting it may be beneficial for treating inflammatory bowel diseases beyond its antibacterial properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulatory effects of ciprofloxacin in TNBS-induced colitis in mice. Lahat, G., Halperin, D., Barazovsky, E., et al.[2018]

Ciprofloxacin is an effective antibiotic for treating a variety of infections, including osteomyelitis, gonorrhea, and infections of the urinary and gastrointestinal tracts, with data from 2,018 patients showing its broad-spectrum activity against multiple bacteria.

In controlled trials, ciprofloxacin demonstrated comparable or superior safety and efficacy compared to other antibiotics like trimethoprim-sulfamethoxazole and ampicillin, with mild adverse reactions and rare emergence of resistance, making it a reliable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety, and potential economic benefits of oral ciprofloxacin in the treatment of infections. Sanders, WE.[2019]

Pefloxacin demonstrated strong in-vitro antimicrobial activity against various medically important bacteria, with low minimum inhibitory concentrations (MIC90) indicating effectiveness, particularly against Enterobacteriaceae and Staphylococci.

Ciprofloxacin was found to be the most active among the newer fluorinated quinolones tested, while older non-fluorinated quinolones were only effective against Enterobacteriaceae at concentrations that could be achieved in urine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In-vitro activity of pefloxacin compared with six other quinolones. Ligtvoet, EE., Wickerhoff-Minoggio, T.[2019]

Different quinolone antibiotics have varying absorption rates and bioavailability, with pefloxacin, ofloxacin, and fleroxacin showing nearly 100% bioavailability, while norfloxacin, ciprofloxacin, and enoxacin have incomplete absorption.

Ciprofloxacin is particularly effective against Pseudomonas aeruginosa, offering the best therapeutic ratio, while dosing adjustments are necessary for ofloxacin in patients with renal failure, highlighting the importance of considering patient-specific factors in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacokinetics and tissue penetration of the fluoroquinolones. Bergeron, MG.[2004]

PD127,391, a new 4-quinolone antibiotic, demonstrated broad antimicrobial activity, particularly excelling against gram-positive bacteria, including multidrug-resistant strains, and was highly effective against gram-negative bacteria like Pseudomonas aeruginosa.

In comparison to ciprofloxacin, PD127,391 was significantly more potent against gram-positive isolates and showed superior efficacy against resistant organisms, with all tested bacteria inhibited at concentrations no higher than 2 micrograms/ml.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro activity of PD127,391, a new quinolone against bacterial isolates from cancer patients. Rolston, KV., Ho, DH., LeBlanc, B., et al.[2018]

Citations

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Efficacy of immune checkpoint inhibitors in microsatellite ... This retrospective analysis suggests that ICIs are effective and well tolerated in patients with MSI/dMMR advanced PDAC.

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Rare Pancreatic Cancer Patients Show Strong Response ... The median progression-free survival was 12 months, and most patients were still alive at follow-up, with survival rates of 80% at one year and ...

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Pembrolizumab near the end of life in patients with ... This multisite study examined consecutive pancreas cancer patients, who received pembrolizumab from 2004 through 2022. Median overall survival of > 4 months ...

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Clinical outcomes of immunotherapy in metastatic ... The median overall survival was 7.9 months, and the median progressive-free survival was 4.6 months. The pooled overall response rate was ...

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The Role of Immunotherapy in Pancreatic Cancer - PMC Collectively, these authors concluded that combining CTLA-4 inhibitors with gemcitabine was safe and tolerable. Unfortunately, the responses and clinical ...

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NCT02826486 | Study Assessing Safety and Efficacy of ... This study will assess the efficacy and safety of BL-8040 in combination with pembrolizumab (Keytruda®) and BL-8040/ Pembrolizumab in combination with liposomal ...

8. onclive.com onclive.com/view/bxcl701-plus-pembrolizumab-is-safe-and-generates-early-antitumor-activity-in-advanced-pdac

BXCL701 Plus Pembrolizumab is Safe and Generates ... Benjamin A. Weinberg, MD, FACP, discusses the potential role of BXCL701 plus pembrolizumab in advanced pancreatic ductal adenocarcinoma.

9. oncologynewscentral.com oncologynewscentral.com/pancreatic-cancer/fda-actions-survival-data-and-more-pancreatic-cancer-news-rapid-roundup

FDA Actions, Survival Data, and More: Pancreatic Cancer ... The drug showed promising clinical activity and a manageable safety profile in heavily pretreated patients, according to new data. Further ...

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Treatment Innovations in Pancreatic Cancer The anti–PD-1 antibody pembrolizumab was US Food and Drug Administration (FDA) approved in 2017 for the treatment of advanced, microsatellite ...