A Study of Live Biotherapeutic Product MRx0518 With Hypofractionated Radiation Therapy in Resectable Pancreatic Cancer
Phase 1
Terminated
- Conditions
- Pancreatic Cancer
- Interventions
- Radiation: Hypofractionated Preoperative Radiation
- Registration Number
- NCT04193904
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 13
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description MRx0518 with hypofractionated preoperative radiation 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. MRx0518 with hypofractionated preoperative radiation MRx0518 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.
- Primary Outcome Measures
Name Time Method To assess the safety of MRx0518 in combination with hypofractionated preoperative radiation through the collection of adverse events Up to 1 year post completion of radiation Adverse events will be assessed as per CTCAE v5.0
- Secondary Outcome Measures
Name Time Method Major pathologic response At time of surgery Major pathologic response is defined as \<5% viable cells in resected tumour specimen
Local Control 6 months post radiation Local control is defined as absence of progression at the primary site and will be assessed with imaging
Distant Control 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
Overall Survival (OS) 12 months post radiation OS is defined as the duration from the start of study treatment until death due to any cause
Margin status At time of surgery The margin status of the tumour at the time of surgery will be assessed
Tumour infiltrating lymphocytes (TILs) Baseline to Surgery Changes in TILs from optional baseline biopsy to resected tumour specimen will be assessed.
Progression Free Survival (PFS) 12 months post radiation PFS is defined as the duration from the start of study treatment until disease progression or death
Trial Locations
- Locations (1)
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States