MRx0518 in Patients With Solid Tumours Waiting Surgical Removal of the Tumour (MICROBIOME)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03934827|
Recruitment Status : Recruiting
First Posted : May 2, 2019
Last Update Posted : May 14, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Melanoma Breast Cancer Uterine Cancer Ovarian Cancer Prostate Cancer Urethral Cancer Bladder Cancer Renal Cancer Lung Cancer Head and Neck Cancer||Drug: MRx0518 Capsules Drug: MRx0518/placebo Capsules||Phase 1|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||120 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||20 participants will receive open label MRx0518 in an initial preliminary safety phase. A further 100 participant will then receive MRx0518/Placebo in a 4:1 ratio in a double blinded randomised phase.|
|Masking:||Double (Participant, Investigator)|
|Masking Description:||Part A: open Label; Part B: double blinded|
|Official Title:||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.|
|Actual Study Start Date :||April 10, 2019|
|Estimated Primary Completion Date :||August 2021|
|Estimated Study Completion Date :||February 2022|
Experimental: Part A
Open label, preliminary phase
Drug: MRx0518 Capsules
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
Drug: MRx0518/placebo Capsules
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.
- 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
- 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).
- 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.
- 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.
- 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.
- 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).
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03934827
|Contact: Anna Kasim||+44(0)20 3313 firstname.lastname@example.org|
|Contact: Gayle Fyvie||+44(0)11 3895 email@example.com|
|Imperial College Healthcare NHS Trust||Recruiting|
|London, United Kingdom|
|Principal Investigator: Dr Krell|
|Principal Investigator:||Dr Jonathan Krell||Imperial College London|