Pembrolizumab + Chemotherapy for Pancreatic Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Deirdre Cohen, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

A multi-institutional, single arm pilot study of antibiotics and pembrolizumab, following chemotherapy for the treatment of surgically resectable pancreatic cancer.

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.

What data supports the effectiveness of the drug Pembrolizumab + Chemotherapy for Pancreatic Cancer?

Ciprofloxacin, a component of the treatment, has shown effectiveness in treating various bacterial infections and has potential anti-inflammatory effects, which might contribute to its role in combination therapies. Additionally, ciprofloxacin combined with metronidazole has been effective in treating complicated intra-abdominal infections, suggesting its potential benefit in complex treatment regimens. ^{1 2 3 4 5}

What makes the drug Pembrolizumab unique for treating pancreatic cancer?

Pembrolizumab is an immunotherapy drug that works by helping the immune system recognize and attack cancer cells, which is different from traditional chemotherapy that directly kills cancer cells. This combination of Pembrolizumab with chemotherapy is a novel approach for pancreatic cancer, aiming to enhance the effectiveness of treatment by using both the body's immune response and direct cancer cell targeting. ^{1 2 4 6 7}

Research Team

Deirdre Cohen, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

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.

Trial Timeline

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)

Treatment Details

Interventions

• Ciprofloxacin (Antibiotic)
• Metronidazole (Antibiotic)
• Pembrolizumab (PD-1 Inhibitor)

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.

Participant Groups

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+

Dr. Brendan Carr

Icahn School of Medicine at Mount Sinai

Chief Executive Officer since 2024

MD, MA, MS

Dr. Vicki LoPachin

Icahn School of Medicine at Mount Sinai

Chief Medical Officer

MD, FACP, MBA

Findings from Research

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]

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 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]

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]

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]

References

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

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

2. United States 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. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

In vitro activity of PD127,391, a new quinolone against bacterial isolates from cancer patients. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

The in vitro and in vivo activity of ciprofloxacin. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Immunomodulatory effects of ciprofloxacin in TNBS-induced colitis in mice. [2018]

6. England pubmed.ncbi.nlm.nih.gov

In-vitro activity of pefloxacin compared with six other quinolones. [2019]

7. Canada pubmed.ncbi.nlm.nih.gov

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