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

NCT04193904 | Terminated Phase 1 FDA Drug

• 1 other identifier: MRx0518-I-003
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• To assess the safety of MRx0518 in combination with hypofractionated preoperative radiation through the collection of adverse events

  Adverse events will be assessed as per CTCAE v5.0

  Up to 1 year post completion of radiation

Secondary Outcomes (7)

• Major pathologic response

  At time of surgery

• Tumour infiltrating lymphocytes (TILs)

  Baseline to Surgery

• Overall Survival (OS)

  12 months post radiation

• Progression Free Survival (PFS)

  12 months post radiation

• Local Control

  6 months post radiation

Other Outcomes (5)

• Changes to microbiome

  Baseline to 6 months post completion of radiation

• Tumour immune infiltration

  Baseline to Surgery

• Landscape of immune and stromal cells

  Baseline to Surgery

Study Arms (1)

MRx0518 with hypofractionated preoperative radiation

EXPERIMENTAL

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; Radiation: Hypofractionated Preoperative Radiation

Interventions

MRx0518 DRUG

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.

MRx0518 with hypofractionated preoperative radiation

Hypofractionated Preoperative Radiation RADIATION

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

MRx0518 with hypofractionated preoperative radiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• 4D pharma plc: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Cullen M Taniguchi, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2019
• First Posted: December 10, 2019
• Study Start: December 20, 2019
• Primary Completion: May 8, 2023
• Study Completion: May 8, 2023
• Last Updated: June 2, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)