Metastatic Colorectal CancerPhase 2NCT01539824
A Study of IMM-101 in Combination With Radiation Induced Tumour Necrosis in Colorectal Cancer
A Phase 2 study testing Mycobacterium obuense and SBRT in people with Metastatic Colorectal Cancer, run by Immodulon Therapeutics Ltd at 2 sites in United Kingdom.
Trial summary
The purpose of this study is to investigate the safety and effects of IMM 101 in combination with a single targeted dose of radiation in patients with metastatic colorectal cancer in whom chemotherapy or other treatment has not been effective. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Mycobacterium obuense and SBRT
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 30 May 2012to 27 Mar 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Male or female; aged ≥ 18 years. Histologically confirmed colorectal adenocarcinoma. Documented evidence of disease progression following at least one line of chemotherapy.
- No further standard chemotherapy options available have refused further chemotherapy.
- Metastatic lesions in at least two sites in the liver (+/- other sites) suitable for bidimensional and volumetric evaluation by CT scan.
- World Health Organization (WHO) performance status of 0-2. Cockcroft calculated Glomerular Filtration Rate of > 40mL/min at screening. Life expectancy, in the opinion of the Investigator, of > 3 months from screening.
Who cannot join
- Evidence of central nervous system metastasis. Severe, active uncontrolled infection requiring systemic antibiotics, antiviral or antifungal treatments.
- Any previous or concurrent malignancy, except adequately treated carcinoma in situ of the cervix, basal cell carcinoma of the skin and/or non-melanoma skin cancer, or if previous malignancy was more than 5 years earlier and there are no signs of recurrence.
- Serum albumin < 30 g/L at screening. C-reactive protein (CRP) > 70 mg/L at screening. Transaminases (ALT or AST) > 5 X Upper Limit of Normal at screening. Bilirubin level > 2 X Upper Limit of Normal at screening. Radiotherapy in the 12 weeks before screening. Depot corticosteroid use in the 6 weeks before screening. Chronic use of any systemic corticosteroids (> 10 mg per day of prednisolone or equivalent for a period of 2 weeks or more) and/or immunosuppressant drugs (such as azathioprine, tacrolimus, cyclosporin) within the 2-week period before the first administration of study drug.
- Woman of child-bearing potential who is not using an approved method of birth control Any investigational product administration in the 3 months before screening. Contraindication to CT scan, e.g., allergy to iodine based contrast medium. A surgical or medical condition which, in the judgement of the Investigator, might interfere with the activity of IMM-101, or with the performance of this study.
- Any uncontrolled concomitant disease which, in the judgement of the Investigator, might interfere with the activity of IMM-101, or with the performance of this study.
- History of serious adverse reaction or serious hypersensitivity to any drug that in the opinion of the Investigator may raise a safety concern.
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- Any previous treatment with IMM-101 or related mycobacterial immunotherapy (prior bacillus Calmette-Guerin (BCG) vaccination against Tuberculosis is allowed).
- Known history of human immunodeficiency virus (HIV) or syphilis, current symptomatic Hepatitis B or C.
- Unable or unwilling to comply with the protocol.
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
HCA International, The Sarah Cannon Research Institute
London, W1G 6AD
The London Clinic
London
About this study
Official title: A Phase II, Single Arm, Investigative Study of IMM-101 in Combination With Radiation Induced Tumour Necrosis in Patients With Previously Treated Colorectal Cancer
The purpose of this study is to investigate the safety and effects of IMM 101 in combination with a single targeted dose of radiation in patients with metastatic colorectal cancer in whom chemotherapy or other treatment has not been effective. Administration of radiation (using the CyberKnife) to the target tumour growth in the liver results in the release of tumour material. IMM-101 may help the immune system to react to the tumour material released from the damaged tumour, and so have a beneficial effect in slowing down the rate of growth of other tumour growths in the liver and other organs.
Read the detailed description
Radiotherapy given in standard fractionation regimes leads to cell death by causing double stranded DNA breaks via production of oxygen free radicals. At the very high doses of stereotactic body radiotherapy (SBRT) administered with extreme accuracy in a single fraction by the CyberKnife system, there is induction of tumour necrosis due to endothelial cell damage and vascular collapse, cell membrane breakdown, and the release of cellular material and tumour antigens into the circulation, in addition to DNA strand breaks. It is hypothesised that the combination of modulation of the body's immune responses in the presence of an increased exposure to tumour antigen will provide sufficient induction of the immune system to suppress tumour growth.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Mycobacterium obuense, SBRT
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mycobacterium obuenseBiological
Also called IMM-101
IMM-101 is a suspension of heat-killed whole cell M. obuense in borate-buffered saline.
SBRTRadiation
Also called stereotactic body radiation, CyberKnife
The CyberKnife system is normally used for the treatment of cancerous tumours in cases where the type and position of the tumour and the condition of the patient indicate that treatment may be curative. In this study, the CyberKnife is being used in an experimental way to deliver a targeted dose of stereotactic body radiation with extreme accuracy in order to damage a single tumour growth (metastasis) in the liver.
| Study group | Role | What they receive |
|---|---|---|
| IMM-101 plus SBRT | Experimental | The treatment regimen with IMM-101 (Mycobacterium obuense) will be every 2 weeks for the first three doses with the last of these doses being on the same day as the radiotherapy by CyberKnife treatment on a liver lesion targeted by the Principal Investigator. Following a rest of 4 weeks, patients will again receive IMM-101 every 2 weeks for the next 3 doses followed by a further 4 weeks rest. Thereafter, IMM-101 will be given at 4 week intervals for up to 12 months or until patient withdrawal for any reason Receives: Biological: Mycobacterium obuense; Radiation: SBRT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease Stabilisation Rate
The disease stabilisation rate at 24 weeks defined as the proportion of patients with a complete response, partial response or stable disease in accordance with immune-related response criteria.
Measured: 24 weeks
Secondary outcomes (6)
Safety and Tolerability Profiles
Safety and tolerability profiles as judged by:
Local and systemic toxicities. Number, type and degree of toxicities as measured by the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) v4.0.
Safety and tolerability are be monitored through the study by a Data Monitoring Committee (DMC)
Measured: 48 weeks
Objective Response Rate
Patients with an objective response were those who had a complete (CR) or partial response (PR), or stable disease(SD) based on CT scan findings, absence of clinical signs and symptoms of progression, did not withdraw due to disease progression prior to/at the Week 12/ 24 /36 / 48 assessment and were alive at the relevant assessment point
Measured: 12, 24, 36 and 48 weeks
Disease Stabilisation Rate
Patients with disease stabilisation were those who had CR, PR, or SD based on CT scan findings, absence of clinical signs and symptoms of progression, did not withdraw due to disease progression prior to/at the Week 24, 36 or 48 assessment and were alive at the respective assessment.
Measured: 12, 36 and 48 weeks
Overall Disease Stabilisation Rate
The overall disease stabilisation rate was recorded as the percentage of patients with a CR, PR or SD as best overall response and was to be assessed at 12, 24 (primary time point), 36 and 48 weeks and overall.
Measured: 12, 36 and 48 weeks.
Overall Response Rate
The overall response rate will be recorded as the percentage of patients with a CR or PR as best overall response.
Measured: 12, 24, 36 and 48 weeks.
Survival
The number of patients alive at 12, 24, 36 \& 48 weeks. Patients without a date of death were to be censored at the date the patient was last known to be alive. The protocol made provision for patients to continue to be followed up and data to be collected, post study withdrawal.
Measured: 12, 24, 36 and 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2012 (estimated)
- Study start30 May 2012
- Primary completion27 Mar 2014
- Study completion27 Mar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Immodulon Therapeutics Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Andrew Gaya, Principal investigator, Leaders In Oncology Care, Harley St, London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01539824
- Sponsor's protocol ID
- IMM-101-007
- Other IDs
- 2011-003958-85
- Status last verified
- Oct 2024
- First submitted
- 22 Feb 2012
- Last updated
- 25 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Single Arm, Investigative Study of IMM-101 in Combination With Radiation Induced Tumour Necrosis in Patients With Previously Treated Colorectal Cancer
- ClinicalTrials.gov ID
- NCT01539824
- Acronym / sponsor ID
- IMM-101-007
- Conditions
- Metastatic Colorectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Immodulon Therapeutics LtdIndustry (pharma, biotech, devices)
- Study start
- 30 May 2012 (actual)
- Primary completion
- 27 Mar 2014 (actual)
- Study completion
- 27 Mar 2014 (actual)
- First posted
- 28 Feb 2012 (estimated)
- Results
- Posted 25 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to investigate the safety and effects of IMM 101 in combination with a single targeted dose of radiation in patients with metastatic colorectal cancer in whom chemotherapy or other treatment has not been effective. Administration of radiation (using the CyberKnife) to the target tumour growth in the liver results in the release of tumour material. IMM-101 may help the immune system to react to the tumour material released from the damaged tumour, and so have a beneficial effect in slowing down the rate of growth of other tumour growths in the liver and other organs.
Detailed description
Radiotherapy given in standard fractionation regimes leads to cell death by causing double stranded DNA breaks via production of oxygen free radicals. At the very high doses of stereotactic body radiotherapy (SBRT) administered with extreme accuracy in a single fraction by the CyberKnife system, there is induction of tumour necrosis due to endothelial cell damage and vascular collapse, cell membrane breakdown, and the release of cellular material and tumour antigens into the circulation, in addition to DNA strand breaks. It is hypothesised that the combination of modulation of the body's immune responses in the presence of an increased exposure to tumour antigen will provide sufficient induction of the immune system to suppress tumour growth.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IMM-101 plus SBRT | Experimental | Biological: Mycobacterium obuense, Radiation: SBRTThe treatment regimen with IMM-101 (Mycobacterium obuense) will be every 2 weeks for the first three doses with the last of these doses being on the same day as the radiotherapy by CyberKnife treatment on a liver lesion targeted by the Principal Investigator. Following a rest of 4 weeks, patients will again receive IMM-101 every 2 weeks for the next 3 doses followed by a further 4 weeks rest. Thereafter, IMM-101 will be given at 4 week intervals for up to 12 months or until patient withdrawal for any reason |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male or female; aged ≥ 18 years. Histologically confirmed colorectal adenocarcinoma. Documented evidence of disease progression following at least one line of chemotherapy.
- No further standard chemotherapy options available have refused further chemotherapy.
- Metastatic lesions in at least two sites in the liver (+/- other sites) suitable for bidimensional and volumetric evaluation by CT scan.
- World Health Organization (WHO) performance status of 0-2. Cockcroft calculated Glomerular Filtration Rate of > 40mL/min at screening. Life expectancy, in the opinion of the Investigator, of > 3 months from screening.
Key exclusion criteria (9 listed)
- Evidence of central nervous system metastasis. Severe, active uncontrolled infection requiring systemic antibiotics, antiviral or antifungal treatments.
- Any previous or concurrent malignancy, except adequately treated carcinoma in situ of the cervix, basal cell carcinoma of the skin and/or non-melanoma skin cancer, or if previous malignancy was more than 5 years earlier and there are no signs of recurrence.
- Serum albumin < 30 g/L at screening. C-reactive protein (CRP) > 70 mg/L at screening. Transaminases (ALT or AST) > 5 X Upper Limit of Normal at screening. Bilirubin level > 2 X Upper Limit of Normal at screening. Radiotherapy in the 12 weeks before screening. Depot corticosteroid use in the 6 weeks before screening. Chronic use of any systemic corticosteroids (> 10 mg per day of prednisolone or equivalent for a period of 2 weeks or more) and/or immunosuppressant drugs (such as azathioprine, tacrolimus, cyclosporin) within the 2-week period before the first administration of study drug.
- Woman of child-bearing potential who is not using an approved method of birth control Any investigational product administration in the 3 months before screening. Contraindication to CT scan, e.g., allergy to iodine based contrast medium. A surgical or medical condition which, in the judgement of the Investigator, might interfere with the activity of IMM-101, or with the performance of this study.
- Any uncontrolled concomitant disease which, in the judgement of the Investigator, might interfere with the activity of IMM-101, or with the performance of this study.
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 |
|---|---|---|
| Mycobacterium obuenseAlso: IMM-101IMM-101 is a suspension of heat-killed whole cell M. obuense in borate-buffered saline. | Biological | IMM-101 plus SBRT |
| SBRTAlso: stereotactic body radiation, CyberKnifeThe CyberKnife system is normally used for the treatment of cancerous tumours in cases where the type and position of the tumour and the condition of the patient indicate that treatment may be curative. In this study, the CyberKnife is being used in an experimental way to deliver a targeted dose of stereotactic body radiation with extreme accuracy in order to damage a single tumour growth (metastasis) in the liver. | Radiation | IMM-101 plus SBRT |
Primary outcome
Disease Stabilisation Rate
Time frame: 24 weeks
The disease stabilisation rate at 24 weeks defined as the proportion of patients with a complete response, partial response or stable disease in accordance with immune-related response criteria.
6 secondary outcomes
Safety and Tolerability Profiles
Time frame: 48 weeks
Objective Response Rate
Time frame: 12, 24, 36 and 48 weeks
Disease Stabilisation Rate
Time frame: 12, 36 and 48 weeks
Overall Disease Stabilisation Rate
Time frame: 12, 36 and 48 weeks.
Overall Response Rate
Time frame: 12, 24, 36 and 48 weeks.
Survival
Time frame: 12, 24, 36 and 48 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Andrew Gaya principal investigator
Leaders In Oncology Care, Harley St, London
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mycobacterium obuense and SBRT in people with Metastatic Colorectal Cancer, run by Immodulon Therapeutics Ltd at 2 sites 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 4 inclusion and 9 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: finished, as of the sponsor's last update on 25 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Disease Stabilisation Rate (time frame: 24 weeks). 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 25 Nov 2024.