Pancreatic CancerPhase 4NCT03891979
Gut Microbiome Modulation to Enable Efficacy of Checkpoint-based Immunotherapy in Pancreatic Adenocarcinoma
A Phase 4 study testing Pembrolizumab, Ciprofloxacin 500mg PO BID days 1-29 and Metronidazole 500mg PO TID days 1-29 in people with Pancreatic Cancer, run by NYU Langone Health at 1 site in United States.
Trial summary
A multi-institutional, single arm pilot study of antibiotics and pembrolizumab for the treatment of surgically resectable pancreatic cancer. The primary purpose of this study is to determine the change in immune activation in pancreatic tumor tissue following treatment with antibiotics and pembrolizumab. Read more about this study
- Who is it for?
- Ages 18 months to 100 years
- Conditions the study is for
- Pancreatic Cancer
- What is being tested?
- Pembrolizumab, Ciprofloxacin 500mg PO BID days 1-29 and Metronidazole 500mg PO TID days 1-29
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Jun 2019to 1 Jun 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 18 months to 100 years
- All sexes
- No healthy volunteers
- Child, 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 I and II disease (per AJCC 8th ed)
- Resectable pancreatic cancer as defined by NCCN Guidelines 1.2018 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
- Patients must agree to pre-treatment biopsy and definitive surgical resection
Show all 26Show fewer
- ECOG performance status of 0 or 1
- No prior treatment for diagnosis of pancreatic cancer
- Normal organ and marrow function
- Absolute neutrophil count (ANC) ≥1500/µL
- Platelets ≥100 000/µL
- Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La
- Renal Creatinine OR Measured or calculated by creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR
- ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN
- Hepatic 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
- Coagulation 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
- ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal.
- Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
- Creatinine clearance (CrCl) should be calculated per institutional standard. 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 (see Appendix 1), not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) as defined in Appendix 1 OR
- A WOCBP who agrees to follow the contraceptive guidance in Appendix 1 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 instructions for method(s) of contraception (see Appendix 1) for the duration of treatment with study treatment(s) and for a total of 180 days posttreatment 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 (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
- 4. Medical history and concurrent disease as below:
- Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study treatment administration except for adrenal replacement steroid doses > 10 mg daily prednisone equivalent in the absence of active autoimmune disease.
- Note: Treatment with a short course of steroids (< 5 days) up to 7 days prior to initiating study treatment is permitted. Participants with asthma that require intermittent use intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study.
Show all 34Show fewer
- Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity.
- Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:
- Myocardial infarction or stroke/transient ischemic attack within the past 6 months
- Uncontrolled angina within the past 3 months
- Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
- History of other clinically significant heart disease (eg, cardiomyopathy, congestive heart failure with New York Heart Association functional classification III to IV, pericarditis, significant pericardial effusion, or myocarditis)
- Cardiovascular disease-related requirement for daily supplemental oxygen therapy.
- 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. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, euthyroid participants with a history of Grave's disease (participants with suspected autoimmune thyroid disorders must be negative for thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin prior to first dose of study treatment), psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll after discussing with the Principal Investigator.
- Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. *Note: for those participants who will be undergoing planned splenectomy, vaccinations against S. pneumoniae, N. meningitidis, H. influenzae type b and influenza virus should be administered at least 2 weeks after the surgical intervention.
- Known human immunodeficiency virus (HIV), known active hepatitis A, or known hepatitis B or C infection.
- 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
- Pregnant or lactating women
- A WOCBP who has a positive urine pregnancy test within 72 hours or no pregnancy test prior to registration (see Appendix 1). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Note: in the event that >72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
- WOCBP who are unwilling or unable to use an acceptable method to minimize the risk of pregnancy (see Appendix 1) 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 as described in section 20.
- 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 that required steroids or has current pneumonitis.
- 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.
About this study
Official title: A Pilot Study of Gut Microbiome Modulation to Enable Efficacy of Checkpoint-based Immunotherapy in Pancreatic Adenocarcinoma
A multi-institutional, single arm pilot study of antibiotics and pembrolizumab for the treatment of surgically resectable pancreatic cancer. The primary purpose of this study is to determine the change in immune activation in pancreatic tumor tissue following treatment with antibiotics and pembrolizumab.
- Conditions
- Pancreatic Cancer
- Being tested
- Pembrolizumab, Ciprofloxacin 500mg PO BID days 1-29, Metronidazole 500mg PO TID days 1-29
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Pembrolizumab will be given for two doses every 3 weeks starting on day 8 (ie days 8 and 29). Antibiotics will continue throughout the entire four week pre-operative period.
Ciprofloxacin 500mg PO BID days 1-29; Metronidazole 500mg PO TID days 1-29; Pembrolizumab 200mg IV days 8 and 29.
Ciprofloxacin 500mg PO BID days 1-29Drug
Antibiotics will continue throughout the entire four week pre-operative period.
Metronidazole 500mg PO TID days 1-29Drug
Antibiotics will continue throughout the entire four week pre-operative period.
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab + Antibiotics | Experimental | Pembrolizumab will be given for two doses every 3 weeks starting on day 8 (ie days 8 and 29). Antibiotics will continue throughout the entire four week pre-operative period. Receives: Drug: Pembrolizumab; Drug: Ciprofloxacin 500mg PO BID days 1-29; Drug: Metronidazole 500mg PO TID days 1-29 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in immune activation in pancreatic tumor tissue following treatment with antibiotics and pembrolizumab measured by activation of HLA-DR,
activation is defined as an increase of 20% or more over baseline in percentage of T cells expressing the marker.
Measured: 12 Weeks
Change in immune activation in pancreatic tumor tissue following treatment with antibiotics and pembrolizumab measured by activation of
activation is defined as an increase of 20% or more over baseline in percentage of T cells expressing the marker.
Measured: 12 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2019
- Study start25 Jun 2019
- Primary completion1 Jun 2020
- Study completion1 Jun 2020
Why it stopped: Suspended due to Primary Investigator's decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Deidre Cohen, Principal investigator, New York Langone Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03891979
- Sponsor's protocol ID
- 18-00137
- Status last verified
- Jun 2020
- First submitted
- 25 Mar 2019
- Last updated
- 26 Jun 2020
- Results posted
- No
- Data monitoring committee
- No
- 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).
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Gut Microbiome Modulation to Enable Efficacy of Checkpoint-based Immunotherapy in Pancreatic Adenocarcinoma
- ClinicalTrials.gov ID
- NCT03891979
- Acronym / sponsor ID
- 18-00137
- Conditions
- Pancreatic Cancer
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Suspended due to Primary Investigator's decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Study start
- 25 Jun 2019 (actual)
- Primary completion
- 1 Jun 2020 (actual)
- Study completion
- 1 Jun 2020 (actual)
- First posted
- 27 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A multi-institutional, single arm pilot study of antibiotics and pembrolizumab for the treatment of surgically resectable pancreatic cancer. The primary purpose of this study is to determine the change in immune activation in pancreatic tumor tissue following treatment with antibiotics and pembrolizumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab + Antibiotics | Experimental | Drug: Pembrolizumab, Drug: Ciprofloxacin 500mg PO BID days 1-29, Drug: Metronidazole 500mg PO TID days 1-29Pembrolizumab will be given for two doses every 3 weeks starting on day 8 (ie days 8 and 29). Antibiotics will continue throughout the entire four week pre-operative period. |
Who may qualify
- Ages
- 18 months to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (26 listed)
- 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 I and II disease (per AJCC 8th ed)
- Resectable pancreatic cancer as defined by NCCN Guidelines 1.2018 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
Key exclusion criteria (34 listed)
- 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 (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
- Note: Treatment with a short course of steroids (< 5 days) up to 7 days prior to initiating study treatment is permitted. Participants with asthma that require intermittent use intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study.
- Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabPembrolizumab will be given for two doses every 3 weeks starting on day 8 (ie days 8 and 29). Antibiotics will continue throughout the entire four week pre-operative period. Ciprofloxacin 500mg PO BID days 1-29; Metronidazole 500mg PO TID days 1-29; Pembrolizumab 200mg IV days 8 and 29. | Drug | Pembrolizumab + Antibiotics |
| Ciprofloxacin 500mg PO BID days 1-29Antibiotics will continue throughout the entire four week pre-operative period. | Drug | Pembrolizumab + Antibiotics |
| Metronidazole 500mg PO TID days 1-29Antibiotics will continue throughout the entire four week pre-operative period. | Drug | Pembrolizumab + Antibiotics |
Primary outcome
Change in immune activation in pancreatic tumor tissue following treatment with antibiotics and pembrolizumab measured by activation of HLA-DR,
Time frame: 12 Weeks
activation is defined as an increase of 20% or more over baseline in percentage of T cells expressing the marker.
Change in immune activation in pancreatic tumor tissue following treatment with antibiotics and pembrolizumab measured by activation of
Time frame: 12 Weeks
activation is defined as an increase of 20% or more over baseline in percentage of T cells expressing the marker.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2020.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Related trials for Pancreatic Cancer
Active, not recruitingPhase 2
Cisplatin and Etoposide Versus Temozolomide and Capecitabine in Patients With Advanced Poorly Differentiated (G3) Non-Small Cell Gastrointestinal Neuroendocrine Carcinomas
Gastric Neuroendocrine Carcinoma, Intestinal Neuroendocrine Carcinoma
RecruitingPhase 1/2
Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12V Variant of Mutated RAS in HLA-A*11:01 Patients
Pancreatic Cancer, Gastric Cancer
RecruitingPhase 1
Metarrestin (ML-246) in Subjects With Metastatic Solid Tumors
Advanced Solid Tumors, Metastatic Pancreatic Cancer
Active, not recruitingPhase 2
Combination Immunotherapy Plus Standard-of-Care Chemotherapy Versus Standard-of-Care Chemotherapy for the Treatment of Locally Advanced or Metastatic Pancreatic Cancer
Pancreatic Cancer
Active, not recruitingPhase 2
A Phase 2 Study of T-DXd in Patients With Selected HER2 Expressing Tumors
Part 1: Bladder, Biliary Tract, Cervical, Endometrial, Ovarian, Pancreatic Cancer, Rare Tumors, Any Tumor Type Excluding Breast, Gastric, Colorectal Cancer, Part 2: HER2 Expressing/Amplified Solid Tumors Excluding Breast, Gastric, Colorectal Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Deidre Cohen principal investigator
New York Langone Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pembrolizumab, Ciprofloxacin 500mg PO BID days 1-29 and Metronidazole 500mg PO TID days 1-29 in people with Pancreatic Cancer, run by NYU Langone Health 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 26 inclusion and 34 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: withdrawn, as of the sponsor's last update on 26 Jun 2020. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in immune activation in pancreatic tumor tissue following treatment with antibiotics and pembrolizumab measured by activation of HLA-DR, (time frame: 12 Weeks). 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?
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 26 Jun 2020; AzTrials last refreshed its copy on 3 Nov 2026.