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

NCT03934827 | Unknown Phase 1 DMC

• 1 other identifier: C/35/2017
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Cancer; Solid Tumour

Outcome Measures

Primary Outcomes (5)

• Safety and tolerability of MRx0518 as determined through the collection of the number and severity of adverse vents (AEs) and serious adverse events (SAEs).

  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.

  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.

  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.

  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.

  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 Outcomes (2)

• Response of MRx0518 determined by the measurement of tumour markers.

  Baseline (optional) and during surgery.

• Overall survival of patients who receive MRx0518 compared to placebo.

  Survival of subjects will be recorded up to 2 years post-surgery

Study Arms (2)

Part A

EXPERIMENTAL

Open label, preliminary phase 20 participants

Drug: MRx0518 Capsules

Part B

EXPERIMENTAL

Randomised, double blinded phase 100 participants

Drug: MRx0518/placebo Capsules

Interventions

MRx0518 Capsules DRUG

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.

Part A

MRx0518/placebo Capsules DRUG

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.

Part B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Imperial College London: lead
• 4D pharma plc: collaborator

Study Sites (1)

Imperial College Healthcare NHS Trust

London, United Kingdom

Location

MeSH Terms

Conditions

Melanoma; Breast Neoplasms; Uterine Neoplasms; Ovarian Neoplasms; Prostatic Neoplasms; Urethral Neoplasms; Urinary Bladder Neoplasms; Kidney Neoplasms; Lung Neoplasms; Head and Neck Neoplasms; Neoplasms

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Breast Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Urologic Neoplasms; Urethral Diseases; Urologic Diseases; Urinary Bladder Diseases; Kidney Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Dr Jonathan Krell

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Part A: open Label; Part B: double blinded
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 15, 2019
• First Posted: May 2, 2019
• Study Start: April 10, 2019
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: August 11, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)