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A Study of Live Biotherapeutic Product MRx0518 With Hypofractionated Radiation Therapy in Resectable Pancreatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04193904
Recruitment Status : Recruiting
First Posted : December 10, 2019
Last Update Posted : January 3, 2020
Sponsor:
Information provided by (Responsible Party):
4D pharma plc

Brief Summary:

This is a single center, open-label, phase I study to evaluate the safety and preliminary efficacy of MRx0518 with preoperative hypofractionated radiation in 15 patients with resectable pancreatic cancer.

Subjects will take MRx0518 daily for one week prior to the start of radiation therapy, throughout radiation and until surgical resection of the tumour.


Condition or disease Intervention/treatment Phase
Pancreatic Cancer Drug: MRx0518 Radiation: Hypofractionated Preoperative Radiation Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Safety and Preliminary Efficacy Study of the Oral Live Biotherapeutic MRx0518 With Hypofractionated Preoperative Radiation for Resectable Pancreatic Cancer
Actual Study Start Date : December 20, 2019
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: MRx0518 with hypofractionated preoperative radiation
Subjects will take one capsule of MRx0518 twice daily from one week prior to radiation therapy until surgical resection (6 to 9 weeks approx.) Radiation therapy will be delivered as 30Gy/10 fractions over 2 weeks.
Drug: MRx0518
MRx0518 is a live biotherapeutic product consisting of a lyophilised formulation of a proprietary strain of bacterium. The study dosing regimen is one capsule two times per day for the duration of the treatment period.

Radiation: Hypofractionated Preoperative Radiation
Radiation will be delivered as 30Gy/10 fractions over two weeks.




Primary Outcome Measures :
  1. To assess the safety of MRx0518 in combination with hypofractionated preoperative radiation through the collection of adverse events [ Time Frame: Up to 1 year post completion of radiation ]
    Adverse events will be assessed as per CTCAE v5.0


Secondary Outcome Measures :
  1. Major pathologic response [ Time Frame: At time of surgery ]
    Major pathologic response is defined as <5% viable cells in resected tumour specimen

  2. Tumour infiltrating lymphocytes (TILs) [ Time Frame: Baseline to Surgery ]
    Changes in TILs from baseline biopsy to resected tumour specimen will be assessed.

  3. Overall Survival (OS) [ Time Frame: 12 months post radiation ]
    OS is defined as the duration from the start of study treatment until death due to any cause

  4. Progression Free Survival (PFS) [ Time Frame: 12 months post radiation ]
    PFS is defined as the duration from the start of study treatment until disease progression or death

  5. Local Control [ Time Frame: 6 months post radiation ]
    Local control is defined as absence of progression at the primary site and will be assessed with imaging

  6. Distant Control [ Time Frame: 6 months post radiation ]
    Distant control is defined as absence of progression at any site other than the primary site and will be assessed with imaging

  7. Margin status [ Time Frame: At time of surgery ]
    The margin status of the tumour at the time of surgery will be assessed


Other Outcome Measures:
  1. Changes to microbiome [ Time Frame: Baseline to 6 months post completion of radiation ]
    The microbiome profile of faecal, urine, tumour and duodenum samples will be analysed for changes using the MicroDx platform

  2. Tumour immune infiltration [ Time Frame: Baseline to Surgery ]
    Biopsies and resection specimens will be assessed for changes in tumour immune infiltrates

  3. Landscape of immune and stromal cells [ Time Frame: Baseline to Surgery ]
    Biopsy and resection specimens will be catalogued for the landscape of immune and stromal cells

  4. Changes in Circulating Tumour Cells [ Time Frame: Baseline to 6 months post completion of radiation ]
    Blood samples will be assessed for presence of circulating tumour cells, circulating tumour DNA and/or circulating immune cells

  5. Genomic changes [ Time Frame: Baseline to 6 months post completion of radiation ]
    Whole exome sequencing and transcriptome sequencing from tumour and blood samples will be performed



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient has signed informed consent and is willing to comply with the protocol
  • Cytologic or biopsy confirmed adenocarcinoma of the pancreas
  • TNM stage: Tx, T1-4, N0-1 or Nx, M0
  • Meets criteria for resectable disease per 2019 NCCN guidelines for pancreatic cancer
  • No evidence of distant metastases either prior to or after induction chemotherapy
  • Patient should have a metal stent in place if duodenal stent is required
  • Able to comply with instructions required for radiation therapy
  • Age 18 years or older
  • Completion of 2-6 months of standard induction chemotherapy (mFOLFIRINOX, gemcitabine and nab-paclitaxel or other)
  • Eastern Cooperative Oncology Group Score 0, 1 or 2
  • Adequate haematologic function (absolute neutrophil count ≥1500mm3; haemoglobin ≥8.0 g/dL; platelet count ≥50000mm3)
  • Adequate renal and liver function (creatinine ≤ 1.5 x upper limit of normal; total bilirubin ≤ 1.5 x upper limit of normal; aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x upper limit of normal; alkaline phosphatase ≤ 2.5 x upper limit of normal

Exclusion Criteria:

  • Prior radiation therapy to the abdomen that would overlap with the treatment field
  • Prior surgical resection of pancreatic tumour
  • Receiving any approved or investigational anti-cancer agent other than those provided for in this study
  • Uncontrolled or active gastric or duodenal ulcer disease within 30 days of dosing
  • Direct invasion of the duodenum or stomach by the primary tumour
  • Residual or ongoing ≥Grade 3 toxicity from chemotherapy
  • Contraindication to IV contrast
  • Concurrent participation in another interventional clinical trial or use of another investigational agent within 30 days of consent (concurrent non-interventional trials are eligible)
  • Uncontrolled intercurrent illness including but not limited to, symptomatic congestive heart failure, unstable angina pectoris, renal failure, cardiac arrhythmia, stroke, or psychiatric illness that would limit compliance with treatment
  • Second primary malignancy within the last 5 years, unless treated definitively and/or low risk in the judgement of the treating investigator
  • Known history of HIV or active hepatitis B/C (patients who have been vaccinated for hepatitis B and do not have history of infection are eligible)
  • Known intolerance or hypersensitivity to study drug
  • Subjects who are allergic to amoxicillin/clavulanic acid, erythromycin and imipenem
  • Female subjects who are breastfeeding
  • Women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control for the entire study and for 30 days after last dose of MRx0518. A negative pregnancy test must be obtained within 14 days prior to start of treatment
  • Male subjects who are unwilling or unable to use an acceptable method of birth control for the entire study period and for 30 days after last dose of MRx0518
  • Serious infection requiring systemic therapy
  • Use of systemic antibiotics within 2 weeks of study treatment
  • Has a known inability for intake of oral capsules

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04193904


Contacts
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Contact: Clinical Operations +44(0)1138950130 clinicaltrials@4dpharmaplc.com

Locations
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United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Cullen M Taniguchi, MD         
Sponsors and Collaborators
4D pharma plc
Investigators
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Principal Investigator: Cullen M Taniguchi, MD M.D. Anderson Cancer Center

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Responsible Party: 4D pharma plc
ClinicalTrials.gov Identifier: NCT04193904    
Other Study ID Numbers: MRx0518-I-003
First Posted: December 10, 2019    Key Record Dates
Last Update Posted: January 3, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases