Clinical trial NCT04193904: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Pancreatic Cancer
Lead sponsor: 4D pharma plc
Sponsor class: INDUSTRY
First posted: 2019-12-10
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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
* 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

Primary outcomes:
measure: To assess the safety of MRx0518 in combination with hypofractionated preoperative radiation through the collection of adverse events
timeFrame: Up to 1 year post completion of radiation
Secondary outcomes:
measure: Major pathologic response
timeFrame: At time of surgery
measure: Tumour infiltrating lymphocytes (TILs)
timeFrame: Baseline to Surgery
measure: Overall Survival (OS)
timeFrame: 12 months post radiation
measure: Progression Free Survival (PFS)
timeFrame: 12 months post radiation
measure: Local Control
timeFrame: 6 months post radiation
measure: Distant Control
timeFrame: 6 months post radiation
measure: Margin status
timeFrame: At time of surgery
Other outcomes:
measure: Changes to microbiome
timeFrame: Baseline to 6 months post completion of radiation
measure: Tumour immune infiltration
timeFrame: Baseline to Surgery
measure: Landscape of immune and stromal cells
timeFrame: Baseline to Surgery
measure: Changes in Circulating Tumour Cells
timeFrame: Baseline to 6 months post completion of radiation
measure: Genomic changes
timeFrame: Baseline to 6 months post completion of radiation
Locations:
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Cullen M Taniguchi, MD
role: PRINCIPAL_INVESTIGATOR
References: