MelanomaPhase 1MICROBIOMENCT03934827
MRx0518 in Patients With Solid Tumours Waiting Surgical Removal of the Tumour
A Phase 1 study testing MRx0518 Capsules in people with Melanoma and Breast Cancer, run by Imperial College London at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma, Breast Cancer, Uterine Cancer
- What is being tested?
- MRx0518 Capsules
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 10 Apr 2019to 31 Dec 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
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.
Read the 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).
- Conditions
- Melanoma, Breast Cancer, Uterine Cancer, Ovarian Cancer, Prostate Cancer, Urethral Cancer
- Being tested
- MRx0518 Capsules, MRx0518/placebo Capsules
- Keywords
- Cancer, Solid Tumour
- Medical subject headings
- Melanoma, Breast Neoplasms, Uterine Neoplasms, Ovarian Neoplasms, Prostatic Neoplasms, Urethral Neoplasms, Urinary Bladder Neoplasms, Kidney Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRx0518 CapsulesDrug
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.
MRx0518/placebo CapsulesDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Part A | Experimental | Open label, preliminary phase
20 participants Receives: Drug: MRx0518 Capsules |
| Part B | Experimental | Randomised, double blinded phase
100 participants Receives: Drug: MRx0518/placebo Capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline upto 30 days post surgery.
Secondary outcomes (2)
Response of MRx0518 determined by the measurement of tumour markers.
Tissue biopsies taken at screening (optional) and during surgery and analysed for tumour biomarkers (e.g. Ca125 in gynaecological malignancies, Ca153 in breast cancer).
Measured: Baseline (optional) and during surgery.
Overall survival of patients who receive MRx0518 compared to placebo.
Survival of individual patients will be assessed from the start of treatment until death due to any cause.
Measured: Survival of subjects will be recorded up to 2 years post-surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2019
- Study start10 Apr 2019
- Primary completion31 Dec 2022 (estimated)
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- 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 blind
- Who is masked
- Participant, Investigator
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- 4D pharma plc
- Responsible party
- Sponsor
- Investigators
- Dr Jonathan Krell, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03934827
- Sponsor's protocol ID
- C/35/2017
- Acronym
- MICROBIOME
- Status last verified
- Aug 2022
- First submitted
- 15 Apr 2019
- Last updated
- 11 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT03934827
- Acronym / sponsor ID
- MICROBIOME / C/35/2017
- Conditions
- Melanoma, Breast Cancer, Uterine Cancer, Ovarian Cancer, Prostate Cancer, Urethral Cancer
- Keywords
- Cancer, Solid Tumour
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- 4D pharma plc
- Study start
- 10 Apr 2019 (actual)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 2 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Part A | Experimental | Drug: MRx0518 CapsulesOpen label, preliminary phase 20 participants |
| Part B | Experimental | Drug: MRx0518/placebo CapsulesRandomised, double blinded phase 100 participants |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRx0518 CapsulesMRx0518 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. | Drug | Part A |
| MRx0518/placebo CapsulesMRx0518/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. | Drug | Part B |
Primary outcome
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.
2 secondary outcomes
Response of MRx0518 determined by the measurement of tumour markers.
Time frame: 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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr Jonathan Krell principal investigator
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MRx0518 Capsules in people with Melanoma and Breast Cancer, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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). (time frame: Baseline upto 30 days post surgery.). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2022.