- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03934827
MRx0518 in Patients With Solid Tumours Waiting Surgical Removal of the Tumour (MICROBIOME)
A First in Human, Phase 1 Safety Study in Two Parts to Determine the Safety, Tolerability and Anti-cancer Immune-modulatory Effects of MRx0518 in Patients With Solid Tumour Awaiting Surgical Removal of the Tumour.
The primary objective is to determine the safety and tolerability of the novel compound, MRx0518 in patients with solid tumours at 30 days post-surgery.
20 participants will receive open label MRx0518 in a preliminary safety phase. After successful evaluation by the Independent Safety Monitoring Committee (IDMC), a further 100 participants will be recruited to receive MRx0518/Placebo.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a first in human, single centre study in two parts, which aims to determine the safety and tolerability of the novel biotherapeutic compound, MRx0518, to examine its use as an anti-cancer and immune system modulating agent in patients with a range of solid tumours, over 2 years.
MRx0518 is composed of a proprietary strain of bacterium (Enterococcus species) which is found in the gastrointestinal tract of approx. 25% of humans and is predicted, from preclinical studies, to produce beneficial effects in humans.
Patients who have been diagnosed with melanoma, breast, ovarian, uterine, prostate, urethra, bladder, renal, lung or head and neck cancer, who are amenable to surgical resection, will receive MRx0518 (part A) or MRx0518/placebo (part B) orally twice daily for 2-4 weeks until surgery to remove the tumour. In part A, 20 patients will receive open label MRx0518 as part of a preliminary safety assessment. Following surgery, patients will attend a 30 day, 6 month, 12 month and 24 month follow up visit.
Following successful evaluation of part A data by the Independent Data Monitoring Committee (IDMC) the study will continue to recruit a further 100 patients to Part B of the trial. Part B will be placebo controlled, in which patients will be randomised in a double blinded fashion in a 4:1 ratio of MRx0518:placebo. In total, 120 patients will be recruited into the study (20 from part A and 100 from part B).
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
London, United Kingdom
- Imperial College Healthcare NHS Trust
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 18 years of age or over
- Provide written (signed and dated) informed consent and be capable of understanding the study and co-operating with treatment and follow-up.
- Have radiologically, histologically or cytologically confirmed melanoma, breast, ovarian, uterine, prostate, urethra, bladder, renal, lung, or head and neck cancer* that is considered amenable to primary surgical resection and where primary surgery is planned but would not routinely have been performed until 2-4 weeks post initial biopsy.*New primary cancers or recurrences are permissible provided the patient has not received chemotherapy, radiotherapy or surgery for the last two years prior to screening.
- Have a life expectancy of greater than 12 weeks.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Have normal organ and marrow function.
- Women of child-bearing potential and men must agree to use adequate and highly effective contraception for at least 28 days prior to dosing until one complete menstrual cycle post dosing for women and 3 months after the last dose for men. Alternatively, true abstinence may be used, where this is in line with the preferred and usual lifestyle of the patient.
- Able to swallow and retain oral medication.
Exclusion Criteria:
- Patients who have had any anti-cancer therapy within the last 2 years.
- Patients with cancer affecting the gastrointestinal tract or those where bowel resection is considered to be highly likely to be required.
- Patients may not be receiving any other investigational agents or receiving concurrent anti-cancer therapy. In addition, all herbal (alternative) medicines are excluded.
- Patients not willing, or for whom it is not planned, to undergo primary surgery for their cancer 2-4 weeks after initiation of therapy with IMP.
- Patient who would otherwise have undergone primary surgery within 2 weeks of starting therapy with IMP.
- Patients who have rapidly progressive local disease, or local disease that, in the opinion of the investigator, is not amenable to surgical resection.
- Patients with known structural or valvular heart valve defects, gastrointestinal fistula, feeding tubes and inflammatory bowel disease or those who are immunosuppressed or receiving immunosuppressant medication (steroids up to an equivalent dose of 20mg of prednisolone daily is allowed as long as the dose has been stable for the last 6 months).
- Patients who smoke or use nicotine in any form including e-cigarettes and nicotine patches or sprays or have smoked/used nicotine in the 3 months prior to screening.
- Patients who consume more than 14 units of alcohol per week, on a regular basis.
- History of allergic reactions attributed to compounds of similar biologic composition to MRx0518.
- Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, including patients with active hepatitis B virus (HBV), active hepatitis C virus (HCV) who have a detectable viral load, and patients with Human Immunodeficiency Virus (HIV), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations, gastrointestinal disease that would limit compliance with study requirements.
- Any significant infection e.g. influenza, fever over 38°C, meningitis or an infection resulting in the subject seeking a consultation with a healthcare professional, within four weeks of starting IMP therapy.
- Pregnant women are excluded from this study because teratogenic or abortifacient effects are unknown. Furthermore, there is an unknown but potential risk for adverse events in nursing infants, secondary to treatment of the mother with MRx0518 so breastfeeding should be discontinued if the mother is treated with MRx0518.
- Patients with gastrointestinal disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis).
- Patients who have completed a course of antibiotics within the four weeks before dosing.
- Patients who are allergic to amoxicillin/clavulanic acid, erythromycin and imipenem
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Part A
Open label, preliminary phase 20 participants |
MRx0518 is a live biotherapeutic product consisting of a lyophilised formulation of a proprietary strain of bacterium.
The dosing regimen is one capsule orally twice daily for 2-4 weeks until surgery.
|
Experimental: Part B
Randomised, double blinded phase 100 participants |
MRx0518/placebo product consist of a lyophilised formulation of either a proprietary strain of bacterium or placebo.The dosing regimen is one capsule orally twice daily for 2-4 weeks until surgery.
Placebo capsules are manufactured to mimic MRx0518 capsules and contain the same excipients as the active biotherapeutic product.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety and tolerability of MRx0518 as determined through the collection of the number and severity of adverse vents (AEs) and serious adverse events (SAEs).
Time Frame: Baseline upto 30 days post surgery.
|
AEs and SAEs will be assessed by CTCAE v5.0
|
Baseline upto 30 days post surgery.
|
Safety and tolerability of MRx0518 determined by clinically significant changes in biochemistry, haematology and urinalysis laboratory results.
Time Frame: Baseline upto 30 days post surgery.
|
Assessed by clinically significant changes in biochemistry results (albumin, bilirubin, urea, creatinine, total protein, c reactive protein, calcium, chloride, sodium, phosphorus, potassium, bicarbonate, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl-transferase, globulin, lactate dehydrogenase, creatine kinase, cholesterol, triglycerides, uric acid, and fasting glucose); haematology results (haemoglobin, platelets, RBC, haematocrit, WBC, neutrophils, lymphocytes, monocytes, eosinophils, basophils) and urinalysis results (occult blood, glucose, protein, ketones, nitrite, leucocytes, pH and specific gravity).
|
Baseline upto 30 days post surgery.
|
Safety and tolerability of MRx0518 determined by clinically significant changes in vital signs.
Time Frame: Baseline upto 30 days post surgery.
|
Assessed by the measurement of pulse, blood pressure, temperature and respiratory rate.
|
Baseline upto 30 days post surgery.
|
Safety and tolerability of MRx0518 as determined by clinically significant changes in electrocardiogram (ECG) results.
Time Frame: Baseline upto 30 days years post surgery.
|
Assessed by the measurement of RR interval, PR interval, QRS duration, QT interval and QTc interval.
|
Baseline upto 30 days years post surgery.
|
Safety and tolerability of MRx0518 as determined by clinically significant changes upon physical examination.
Time Frame: Baseline upto 30 days post surgery.
|
Assessed by clinically significant abnormal changes to the general appearance, skin, head and neck, lymph nodes, thyroid, musculoskeletal/extremities, cardiovascular, respiratory, abdomen and neurological assessment.
|
Baseline upto 30 days post surgery.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response of MRx0518 determined by the measurement of tumour markers.
Time Frame: Baseline (optional) and during surgery.
|
Tissue biopsies taken at screening (optional) and during surgery and analysed for tumour biomarkers (e.g.
Ca125 in gynaecological malignancies, Ca153 in breast cancer).
|
Baseline (optional) and during surgery.
|
Overall survival of patients who receive MRx0518 compared to placebo.
Time Frame: Survival of subjects will be recorded up to 2 years post-surgery
|
Survival of individual patients will be assessed from the start of treatment until death due to any cause.
|
Survival of subjects will be recorded up to 2 years post-surgery
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Dr Jonathan Krell, Imperial College London
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- C/35/2017
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Melanoma
-
H. Lee Moffitt Cancer Center and Research InstituteTurnstone Biologics, Corp.RecruitingMetastatic Melanoma | Conjunctival Melanoma | Ocular Melanoma | Unresectable Melanoma | Uveal Melanoma | Cutaneous Melanoma | Mucosal Melanoma | Iris Melanoma | Acral Melanoma | Non-Cutaneous MelanomaUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)CompletedRecurrent Melanoma | Stage IV Melanoma | Mucosal Melanoma | Ciliary Body and Choroid Melanoma, Medium/Large Size | Ciliary Body and Choroid Melanoma, Small Size | Iris Melanoma | Metastatic Intraocular Melanoma | Recurrent Intraocular Melanoma | Stage IV Intraocular Melanoma | Stage IIIA Melanoma | Stage... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Stage IIB Melanoma | Stage IIC Melanoma | Stage IA Melanoma | Stage IB Melanoma | Stage IIA MelanomaUnited States
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI); University of VirginiaCompletedStage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Stage III Skin Melanoma | Stage IIA Skin Melanoma | Stage IIB Skin Melanoma | Stage IIC Skin Melanoma | Stage IIIA Skin Melanoma | Stage IA Skin Melanoma | Stage IB Skin Melanoma | Stage 0 Skin Melanoma | Stage I Skin Melanoma | Stage II Skin MelanomaUnited States
-
MelanomaPRO, RussiaRecruitingMelanoma | Melanoma (Skin) | Melanoma Stage IV | Melanoma Stage III | Melanoma, Stage II | Melanoma, Uveal | Melanoma in Situ | Melanoma, OcularRussian Federation
-
National Cancer Institute (NCI)CompletedStage IV Melanoma | Ciliary Body and Choroid Melanoma, Medium/Large Size | Iris Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Extraocular Extension Melanoma | Stage IIB Melanoma | Stage IIC MelanomaUnited States
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI); National Comprehensive Cancer NetworkTerminatedRecurrent Melanoma | Stage IV Melanoma | Metastatic Intraocular Melanoma | Recurrent Intraocular Melanoma | Stage IV Intraocular Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Extraocular Extension Melanoma | Stage IIIA Intraocular Melanoma | Stage IIIB Intraocular Melanoma | Stage...United States
-
Mayo ClinicNational Cancer Institute (NCI)CompletedRecurrent Melanoma | Stage IV Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Stage IIB Melanoma | Stage IIC Melanoma | Stage IIA MelanomaUnited States
-
Emory UniversityGenentech, Inc.Active, not recruitingStage IV Skin Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Unresectable Melanoma | Stage III Melanoma | Stage IIIA Skin Melanoma | Cutaneous Melanoma, Stage III | Cutaneous Melanoma, Stage IVUnited States
-
BiocadRecruitingMelanoma | Melanoma (Skin) | Melanoma Stage IV | Melanoma Stage III | Melanoma Metastatic | Melanoma Unresectable | Melanoma AdvancedIndia, Russian Federation, Belarus
Clinical Trials on MRx0518 Capsules
-
4D pharma plcTerminatedPancreatic CancerUnited States
-
Reata, a wholly owned subsidiary of BiogenAbbVie; Friedreich's Ataxia Research AllianceActive, not recruitingFriedreich AtaxiaUnited States, Australia, Austria, Italy, United Kingdom
-
Reata, a wholly owned subsidiary of BiogenAbbVieCompletedMItochondrial MyopathiesUnited States, Denmark
-
Reata, a wholly owned subsidiary of BiogenTerminatedConnective Tissue Disease-Associated Pulmonary Arterial HypertensionUnited States, Spain, Japan, Australia, United Kingdom, Canada, Germany, Belgium, Argentina, Israel, Mexico, Brazil, Czechia, Netherlands, Philippines
-
Chinese Academy of Medical Sciences, Fuwai HospitalNot yet recruiting
-
AbbottQuintiles, Inc.Terminated
-
Montefiore Medical CenterCompletedIrritable Bowel SyndromeUnited States
-
Chinese Academy of Medical Sciences, Fuwai HospitalNational Natural Science Foundation of ChinaRecruiting
-
Caelus Pharmaceuticals BVCompleted
-
Massachusetts General HospitalCompleted