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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/16/2021.

MRx0518 in Patients With Solid Tumours Waiting Surgical Removal of the Tumour

Clinicaltrials.gov identifier NCT03934827

Recruitment Status Recruiting

First Posted May 2, 2019

Last update posted May 14, 2019

Study Description

Brief summary:

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:Melanoma
    Breast Cancer
    Uterine Cancer
    Ovarian Cancer
    Prostate Cancer
    Urethral Cancer
    Bladder Cancer
    Renal Cancer
    Lung Cancer
    Head and Neck Cancer
  • Intervention/Treatment: Drug: MRx0518 Capsules
    Drug: MRx0518/placebo Capsules
  • Phase: Phase 1
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 Design
  • Study Type: Interventional
  • Estimated Enrollment: 120 participants
  • Allocation: Randomized
  • 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)
  • Primary Purpose: Treatment
  • 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 2019
  • Estimated Primary Completion Date: August 2021
  • Estimated Study Completion Date: February 2022
Arms and interventions
Arm Intervention/treatment
Experimental: Part A
Open label, preliminary phase 20 participants
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 100 participants
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.
Outcome Measures
  • Primary Outcome Measures: 1. 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
  • 2. 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).
  • 3. 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.
  • 4. 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.
  • 5. 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.
  • Secondary Outcome Measures: 1. 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).
  • 2. 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.
Eligibility Criteria
  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

1. 18 years of age or over

2. Provide written (signed and dated) informed consent and be capable of understanding
the study and co-operating with treatment and follow-up.

3. 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.

4. Have a life expectancy of greater than 12 weeks.

5. Have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2

6. Have normal organ and marrow function.

7. 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.

8. Able to swallow and retain oral medication.

Exclusion Criteria:

1. Patients who have had any anti-cancer therapy within the last 2 years.

2. Patients with cancer affecting the gastrointestinal tract or those where bowel
resection is considered to be highly likely to be required.

3. Patients may not be receiving any other investigational agents or receiving concurrent
anti-cancer therapy. In addition, all herbal (alternative) medicines are excluded.

4. 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.

5. Patient who would otherwise have undergone primary surgery within 2 weeks of starting
therapy with IMP.

6. Patients who have rapidly progressive local disease, or local disease that, in the
opinion of the investigator, is not amenable to surgical resection.

7. 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).

8. 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.

9. Patients who consume more than 14 units of alcohol per week, on a regular basis.

10. History of allergic reactions attributed to compounds of similar biologic composition
to MRx0518.

11. 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.

12. 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.

13. 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.

14. 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).

15. Patients who have completed a course of antibiotics within the four weeks before
dosing.

16. Patients who are allergic to amoxicillin/clavulanic acid, erythromycin and imipenem

Contacts and Locations
Contacts

Contact: Anna Kasim +44(0)20 3313 0648 microbiome-trial@imperial.ac.uk

Contact: Gayle Fyvie +44(0)11 3895 0130 clinicaltrials@4dpharmaplc.com

Locations

United Kingdom
Imperial College Healthcare NHS Trust
London

Sponsors and Collaborators

Imperial College London

4D pharma plc

Investigators

Principal Investigator: Dr Jonathan Krell Imperial College London

More Information
  • Responsible Party: Imperial College London
  • ClinicalTrials.gov Identifier: NCT03934827 History of Changes
  • Other Study ID Numbers: C/35/2017
  • First Posted: May 2, 2019 Key Record Dates
  • Last Update Posted: May 14, 2019
  • Last Verified: May 2019
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: No
  • Studies a U.S. FDA-regulated Drug Product: No
  • Studies a U.S. FDA-regulated Device Product: No
  • Keywords provided by Imperial College London: Cancer Solid Tumour
  • Additional relevant MeSH terms: Kidney Neoplasms
    Urethral Neoplasms
    Uterine Neoplasms