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

• ClinicalTrials.gov Identifier: NCT04193904
• Recruitment Status: Active, not recruiting
• First Posted: December 10, 2019
• Last Update Posted: July 6, 2022
• Sponsor: 4D pharma plc
• Information provided by (Responsible Party): 4D pharma plc

Study Description

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 15 participants
• Allocation: N/A
• 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: January 2023
• Estimated Study Completion Date: October 2023

Arms and Interventions

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.

Outcome Measures

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 optional 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 ]
   Optional 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 ]
   Optional 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

Eligibility Criteria

• 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
• Potentially resectable pancreatic cancer defined as no extra-pancreatic disease, no evidence of tumor extension to the celiac axis, common hepatic artery and superior mesenteric artery, and no evidence of deformity of the superior mesenteric vein or superior mesenteric portal vein confluence
• No evidence of distant metastases either prior to or after induction chemotherapy
• 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 tumor
• 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
• Residual or ongoing ≥Grade 3 toxicity from chemotherapy
• Contraindication to IV contrast that can't be managed with pre-medication
• 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 start of study treatment
• Has a known inability for intake of oral capsules

Contacts and Locations

Locations

United States, Texas

MD Anderson Cancer Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

4D pharma plc

Investigators

• Principal Investigator: Cullen M Taniguchi, MD; M.D. Anderson Cancer Center

More Information

• Responsible Party: 4D pharma plc
• ClinicalTrials.gov Identifier: NCT04193904
• Other Study ID Numbers: MRx0518-I-003
• First Posted: December 10, 2019
• Last Update Posted: July 6, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases