Clinical Trials /

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

NCT04193904

Description:

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.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Live Biotherapeutic Product MRx0518 With Hypofractionated Radiation Therapy in Resectable Pancreatic Cancer
  • Official Title: A Safety and Preliminary Efficacy Study of the Oral Live Biotherapeutic MRx0518 With Hypofractionated Preoperative Radiation for Resectable Pancreatic Cancer

Clinical Trial IDs

  • ORG STUDY ID: MRx0518-I-003
  • NCT ID: NCT04193904

Conditions

  • Pancreatic Cancer

Interventions

DrugSynonymsArms
MRx0518MRx0518 with hypofractionated preoperative radiation

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
MRx0518 with hypofractionated preoperative radiationExperimentalSubjects 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.
  • MRx0518

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Adverse events will be assessed as per CTCAE v5.0

Secondary Outcome Measures

Measure:Major pathologic response
Time Frame:At time of surgery
Safety Issue:
Description:Major pathologic response is defined as <5% viable cells in resected tumour specimen
Measure:Tumour infiltrating lymphocytes (TILs)
Time Frame:Baseline to Surgery
Safety Issue:
Description:Changes in TILs from baseline biopsy to resected tumour specimen will be assessed.
Measure:Overall Survival (OS)
Time Frame:12 months post radiation
Safety Issue:
Description:OS is defined as the duration from the start of study treatment until death due to any cause
Measure:Progression Free Survival (PFS)
Time Frame:12 months post radiation
Safety Issue:
Description:PFS is defined as the duration from the start of study treatment until disease progression or death
Measure:Local Control
Time Frame:6 months post radiation
Safety Issue:
Description:Local control is defined as absence of progression at the primary site and will be assessed with imaging
Measure:Distant Control
Time Frame:6 months post radiation
Safety Issue:
Description:Distant control is defined as absence of progression at any site other than the primary site and will be assessed with imaging
Measure:Margin status
Time Frame:At time of surgery
Safety Issue:
Description:The margin status of the tumour at the time of surgery will be assessed

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:4D pharma plc

Last Updated

December 10, 2019