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

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.

INTRODUCTION

  • Org Study ID: C/35/2017
  • Secondary ID: N/A
  • NTC ID: NCT03934827
  • Sponsor: Imperial College London

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.

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).


  • Overall Status
    Recruiting
  • Start Date
    April 10, 2019
  • Phase
    Phase 1
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Safety and tolerability of MRx0518 as determined through the collection of the number and severity of adverse vents (AEs) and serious adverse events (SAEs).

Primary Outcome 1 - Timeframe: Baseline upto 30 days post surgery.

Primary Outcome 2 - Measure: Safety and tolerability of MRx0518 determined by clinically significant changes in biochemistry, haematology and urinalysis laboratory results.

Primary Outcome 2 - Timeframe: Baseline upto 30 days post surgery.

Primary Outcome 3 - Measure: Safety and tolerability of MRx0518 determined by clinically significant changes in vital signs.

Primary Outcome 3 - Timeframe: Baseline upto 30 days post surgery.

Primary Outcome 4 - Measure: Safety and tolerability of MRx0518 as determined by clinically significant changes in electrocardiogram (ECG) results.

Primary Outcome 4 - Timeframe: Baseline upto 30 days years post surgery.

Primary Outcome 5 - Measure: Safety and tolerability of MRx0518 as determined by clinically significant changes upon physical examination.

Primary Outcome 5 - Timeframe: Baseline upto 30 days post surgery.

CONDITION

  • Melanoma
  • Breast Cancer
  • Uterine Cancer
  • Ovarian Cancer
  • Prostate Cancer
  • Urethral Cancer
  • Bladder Cancer
  • Renal Cancer
  • Lung Cancer
  • Head and Neck Cancer

ELIGIBILITY


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

Gender: All

Minimum Age: N/A

Maximum Age: 18 Years

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Dr Jonathan Krell

Role: Principal Investigator

Affiliation: Imperial College London

Overall Contact

Name: Dr Jonathan Krell

Phone: +44(0)20 3313 0648

Email: microbiome-trial@imperial.ac.uk

LOCATION

Facility Status Contact
Facility: Imperial College Healthcare NHS Trust
London,
United Kingdom 		Status: Recruiting Contact: N/A

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