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Pancreatic CancerPhase 2NCT05462496

Modulation of the Gut Microbiome With Pembrolizumab Following Chemotherapy in Resectable Pancreatic Cancer

A Phase 2 study testing Biopsy, FOLFIRINOX and Ciprofloxacin in people with Pancreatic Cancer, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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

Who is it for?
Ages 19 years and older
Conditions the study is for
Pancreatic Cancer
What is being tested?
Biopsy, FOLFIRINOX and Ciprofloxacin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteUnited States
Study dates
16 Mar 2023to Apr 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed pancreatic adenocarcinoma. Histologies other than adenocarcinoma, or any mixed histologies, will NOT be eligible. *Note: histology must be confirmed prior to study treatment, however, participants may be consented to study based on imaging results consistent with pancreatic adenocarcinoma and then undergo diagnostic and research biopsy simultaneously.
  • Clinical stage T1-3, N0-2, M0 (per AJCC 8th ed)
  • Resectable pancreatic cancer as defined by NCCN Guidelines 2.2021 and based on pancreatic protocol dual-phase CT imaging. Multi-detector computed tomography (MDCT) angiography, performed by acquiring thin, preferably sub-millimeter, axial sections using a dual-phase pancreatic protocol, with images obtained in the pancreatic and portal venous phase of contrast enhancement, is required.
  • No arterial tumor contact (celiac axis [CA], superior mesenteric artery [SMA], or common hepatic artery [CHA])
  • No tumor contact with the superior mesenteric vein (SMV) or portal vein (PV) or ≤180° contact without vein contour irregularity
  • Age > 18 years
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  • Patients must agree to pre-treatment biopsy(which may have been collected on a universal consent), on-treatment biopsy, and definitive surgical resection
  • ECOG performance status of 0 or 1
  • No prior treatment for diagnosis of pancreatic cancer
  • Normal organ and marrow function as defined below:
  • Absolute neutrophil count (ANC) ≥1500/µL
  • Platelets ≥100 000/µL
  • Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L (Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks. )
  • Creatinine ≤1.5 × ULN OR Measured or calculated creatinine clearance (Creatinine clearance (CrCl) should be calculated per institutional standard., GFR can also be used in place of creatinine or CrCl) ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN; ; GFR=glomerular filtration rate; ULN=upper limit of normal .
  • Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN AST (SGOT) and ALT (SGPT) ≤2.5 × ULN; ALT (SGPT) =alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT) =aspartate aminotransferase (serum glutamic oxaloacetic transaminase);
  • International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
  • Note: This table includes eligibility-defining laboratory value requirements for treatment; laboratory value requirements should be adapted according to local regulations and guidelines for the administration of specific chemotherapies.
  • Ability to understand and sign a written informed consent document. Participant must have willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.
  • A female participant is eligible to participate if she is not pregnant , not breastfeeding, and at least one of the following conditions applies:
  • Not a woman of childbearing potential (WOCBP) OR
  • A WOCBP who agrees to follow the study contraceptive guidance during the treatment period and for at least 120 days plus 30 days (a menstruation cycle) after the last dose of study treatment.
  • Males who are sexually active with WOCBP must agree to follow study instructions for method(s) of contraception for the duration of treatment with study treatment(s) and for a total of 180 days post treatment completion. In addition, male participants must be willing to refrain from sperm donation during this time.

Who cannot join

  • Borderline resectable, locally advanced or distant metastatic disease
  • Any medical condition which makes definitive surgical resection of the pancreatic cancer contraindicated due to high risk of morbidity/mortality
  • Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
  • Medical history and concurrent disease as below:
  • -Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg
  • Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity.
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  • Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:
  • Evidence of uncontrolled, active infection, requiring parenteral or oral anti-bacterial, anti-viral or anti-fungal therapy ≤ 28 days prior to screening on study.
  • Participants with a condition requiring chronic systemic oral treatment with either antibiotics or anti-fungals
  • Any uncontrolled inflammatory GI disease including Crohn's Disease and ulcerative colitis.
  • Participants with active, known, or suspected autoimmune disease.
  • Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. *Note: for those participants who will be undergoing planned splenectomy, vaccinations against S. pneumoniae, N. meningitidis, H. influenzae type b and influenza virus may be administered per standard practice.
  • Use of probiotics ≤ 28 days prior to screening on study.
  • Known human immunodeficiency virus (HIV), known active Hepatitis A, or known Hepatitis B
  • History of acute diverticulitis within the last 6 months or current chronic diarrhea
  • Expected to require any other form of antineoplastic or surgical therapy while on study.
  • Pre-existing peripheral neuropathy > Grade 1, as defined by CTCAE v5.0.
  • Pregnant or lactating women.
  • A WOCBP who has a positive urine pregnancy test within 72 hours or no pregnancy test prior to registration.
  • WOCBP who are unwilling or unable to use an acceptable method to minimize the risk of pregnancy for the entire study period and 120 days plus 30 days (a menstruation cycle) after the last dose of study treatment. WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements, but still must undergo pregnancy testing.
  • Sexually active fertile men not using effective birth control if their partners are WOCBP.
  • History of primary immunodeficiency.
  • Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • History of organ allograft or allogeneic bone marrow transplant.
  • Any prior radiation therapy, immunotherapy, or biologic ('targeted') therapy for treatment of the patient's pancreatic tumor. Biliary stent is allowed.
  • Treatment for other invasive carcinomas within the last two years who are at greater than 5% risk of recurrence at time of eligibility screening. Carcinoma in-situ and basal cell carcinoma/ squamous cell carcinoma of the skin are allowed.
  • Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
  • Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment, without complete recovery.
  • History of allergy to study treatments or any of its components.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Deirdre Cohen, MD contact

(212) 824-9331

Deirdre.Cohen@mssm.edu

Rashmi Unawane contact

rashmi.unawane@mssm.edu

United States1 site, 1 recruiting

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

    Katherine Vandris, Katherine.Vandris@mssm.edu

    Deirdre Cohen, MD, Deirdre.Cohen@mssm.edu

    Recruiting

Other trials in United States

About this study

Official title: Pilot Study of Gut Microbiome Modulation to Enable Efficacy of Neoadjuvant Checkpoint-based Immunotherapy Following Chemotherapy in Pancreatic Adenocarcinoma

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

Read the detailed description

Phase: Pilot Study Objectives

Primary Objectives:

  • To determine the change in immune activation in pancreatic tumor tissue following treatment with antibiotics, pembrolizumab.

Secondary Objectives:

  • To establish the safety and feasibility of pre-operative antibiotics in combination with pembrolizumab following chemotherapy
  • To describe the preliminary anti-tumor activity of pre-operative therapy with antibiotics, pembrolizumab, and chemotherapy in subjects with resectable pancreatic cancer

Exploratory Objectives:

  • To determine immunophenotypic changes in the pancreatic tumor microenvironment following depletion of the microbiome using antibiotics and inhibition of PD-1 with pembrolizumab and to correlate these changes with tumor response as measured by histologic regression.
  • To determine changes in systemic immunogenicity as measured in PBMCs harvested from blood following depletion of the microbiome using antibiotics and inhibition of PD-1 with pembrolizumab and to correlate these changes with tumor response as measured by histologic regression.
  • To determine changes in the microbiome as measured in tumor and stool following treatment with chemotherapy, antibiotics, and pembrolizumab and to correlate these changes with tumor response as measured by histologic regression.
  • To correlate changes in immune activation with changes in microbiome abundance and composition.

Methodology: Multi-center, open label, single arm pilot study Endpoint

Primary endpoint:

  • Achievement of immune response, defined as activation of one or more of the following T cell markers: HLA-DR, CD38, CD25, KI67, and CD69; activation is defined as an increase of 20% or more over baseline in percentage of T cells expressing the marker.

Secondary Endpoints:

  • Adverse events graded according to the NCI's Common Terminology Criteria for Adverse Events (CTCAE v5.0).
  • R0 resection rate and histologic regression score
  • Histologic regression score
  • Overall response rate (ORR)
  • Overall survival rate (OS)

Exploratory Endpoints:

  • Immune changes within blood and tissue following treatment and correlate with clinical endpoints
  • Microbiome changes in tissue and stool following treatment and correlate with clinical and immunologic endpoints

Study Duration 5 years Participant Duration 6 months Enrollment Period 2 years Duration of IP administration 1 week

Study Centers/Sites Multicenter:

  1. Mount Sinai Health System, Tisch Cancer Institute
  2. TBD
  3. TBD Number of participants: 25 participants with 11 accrued at Mount Sinai Health over 2 years Description of Study Agent/Procedure: Ciprofloxacin 500 mg PO BID days 63-84. Metronidazole 500 mg PO TID days 63-84. Pembrolizumab 200 mg IV day 70. 5-Fluorouracil 2400 mg/m2 IV 46-48 hours infusion days 1, 15, 28, 42, 56. Leucovorin 400 mg/m2IV days 1, 15, 28, 42, 56. Irinotecan 150 mg/m2IV days 1, 15, 28, 42, 56. Oxaliplatin 85mg/m2IV days 1, 15, 28, 42, 56. Key Procedures: Tumor biopsy, surgical resection, blood draws, and stool collection.

Statistical Analysis: The primary efficacy endpoint is the achievement of immune response, defined as activation of one or more of the following markers: HLA-DR, CD38, CD25, KI67, and CD69; activation is defined as an increase of 20% or more over baseline in percentage of cells expressing the marker. With 25 patients, a 95% exact confidence interval around the immune response rate will be no more than 0.46 units wide.

Being tested
Biopsy, FOLFIRINOX, Ciprofloxacin, Metronidazole, Pembrolizumab
Keywords
Pancreatic cancer, antibiotics, resectable, microbiome, pembrolizumab, chemotherapy
Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BiopsyProcedure or surgery

    Pre-treatment tumor biopsy

  • FOLFIRINOXDrug

    Also called Chemotherapy

    Patients will receive FOLFIRINOX chemotherapy every 2 weeks for 5 cycles. One cycle of mFOLFIRINOX = 14 days.

    Cycles of mFOLFIRINOX are delivered as follows*:

    • Oxaliplatin: 85 mg/m2 IV over 2 hours on Day 1, followed by,
    • Irinotecan: 150 mg/m2 IV over 90 minutes on Day 1, followed by,
    • Leucovorin**: 400 mg/m2 IV over 2 hours on Day 1, followed by,
    • 5FU: 2400 mg/m2 IV over 46-48 hours on Days 1-3

  • CiprofloxacinDrug

    Also called Antibiotic

    Ciprofloxacin and metronidazole will be initiated 7 days following 5th dose of FOLFIRINOX. Subjects will self-administer ciprofloxacin 500mg PO BID on days 1-21. Participants will be instructed to take the antibiotics with food to minimize stomach upset and to administer at the same time each day. Treatment with antibiotics will continue for 21 days unless there is unacceptable toxicity or disease progression. Subjects will record date, time and number of tablets they take on provided drug diaries.

  • MetronidazoleDrug

    Also called Antibiotic

    Ciprofloxacin and metronidazole will be initiated 7 days following 5th dose of FOLFIRINOX. Subjects will self-administer metronidazole 500mg PO every 8 hours on days 1-21. Participants will be instructed to take the antibiotics with food to minimize stomach upset and to administer at the same time each day. Treatment with antibiotics will continue for 21 days unless there is unacceptable toxicity or disease progression. Subjects will record date, time and number of tablets they take on provided drug diaries.

  • PembrolizumabDrug

    Also called Immunotherapy, Monoclonal antibody

    Pembrolizumab will be initiated 7 days post initiation of antibiotics. Subjects will receive a flat dose of pembrolizumab 200mg IV over 30 minutes.

  • Surgical ResectionProcedure or surgery

    Also called pancreaticoduodenectomy, pancreatectomy

    Following completion of 21 days of antibiotics, participant will undergo repeat imaging studies. If there is no progressive disease which renders participant surgically unresectable (based on NCCN guidelines 2.2021), subject will undergo definitive surgical resection.

Study groups in NCT05462496
Study groupRoleWhat they receive
Participants who had Chemotherapy Following Pancreatic AdenocarcinomaExperimentalParticipants to be given antibiotics and pembrolizumab, following chemotherapy for the treatment of surgically resectable pancreatic cancer.
Receives: Procedure: Biopsy; Drug: FOLFIRINOX; Drug: Ciprofloxacin; Drug: Metronidazole; Drug: Pembrolizumab; Procedure: Surgical Resection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Achievement of overall immune response

    Achievement of overall immune response, defined as activation of one or more of the following T cell markers: HLA-DR, CD38, CD25, KI67, and CD69; activation is defined as an increase of 20% or more over baseline in percentage of T cells expressing the marker. Comparison to be made between tissue biopsy taken following chemotherapy (and prior to antibiotics and pembrolizumab) and definitive surgical specimen.

    Measured: at day 43

  2. Achievement of overall immune response

    Achievement of overall immune response, defined as activation of one or more of the following T cell markers: HLA-DR, CD38, CD25, KI67, and CD69; activation is defined as an increase of 20% or more over baseline in percentage of T cells expressing the marker. Comparison to be made between tissue biopsy taken following chemotherapy (and prior to antibiotics and pembrolizumab) and definitive surgical specimen.

    Measured: day 102

Secondary outcomes (5)

  1. Adverse event incidence rate

    Adverse events will be graded according to the NCI's Common Terminology Criteria for Adverse Events (CTCAE v5.0)

    Measured: at 6 months

  2. R0 resection rate

    The R0 Resection Rate (percent) is defined as the percentage of resected specimen that have lateral and deep margins that are free of neoplasia under microscopic visualization.

    Measured: at 3-4 months

  3. Proportion of participants with histologic regression score 0, 1, or 2

    The histologic regression score is defined as the proportion of patients with Grade 0, 1 or 2 histologic tumor response (Grade 0: no viable tumor; Grade 1: <5% viable tumor cells; Grade 2: ≥5% viable tumor cells)

    Measured: at 3-4 months

  4. Overall response rate (ORR)

    The overall response rate (ORR) is defined as the proportion of patients who achieve complete response (CR) or partial response (PR) as per the RECIST 1.1 criteria.

    Measured: at 3-4 months

  5. Overall survival rate (OS)

    Overall survival rate (OS) is defined as the duration of time from initial pembrolizumab administration to the date of death from any cause. Subjects who are alive or lost to follow-up as of the data analysis cutoff date will be censored for OS. The censoring date will be determined from the subject's date of last examination or data analysis cutoff date, whichever event occurs first.

    Measured: at 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jul 2022
  2. Study start16 Mar 2023
  3. Primary completionAug 2027 (estimated)
  4. Study completionApr 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05462496
Sponsor's protocol ID
STUDY-21-01814
Status last verified
Oct 2024
First submitted
11 Jul 2022
Last updated
15 Oct 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biopsy, FOLFIRINOX and Ciprofloxacin in people with Pancreatic Cancer, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 15 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Deirdre Cohen, MD ((212) 824-9331, Deirdre.Cohen@mssm.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Achievement of overall immune response (time frame: at day 43). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05462496.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2024.

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