A Study of IMM-101 in Combination With Radiation Induced Tumour Necrosis in Colorectal Cancer

Phase 2

Completed

Conditions: Metastatic Colorectal Cancer

Interventions: Biological: Mycobacterium obuense
Radiation: SBRT

Registration Number: NCT01539824

Lead Sponsor: Immodulon Therapeutics Ltd

Brief 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. 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 12

Inclusion Criteria

Not provided

Exclusion Criteria

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.

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
IMM-101 plus SBRT	Mycobacterium obuense	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
IMM-101 plus SBRT	SBRT	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

Primary Outcome Measures

Name	Time	Method
Disease Stabilisation Rate	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.

Secondary Outcome Measures

Name	Time	Method
Safety and Tolerability Profiles	48 weeks	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)
Objective Response Rate	12, 24, 36 and 48 weeks	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
Disease Stabilisation Rate	12, 36 and 48 weeks	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.
Overall Disease Stabilisation Rate	12, 36 and 48 weeks.	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.
Overall Response Rate	12, 24, 36 and 48 weeks.	The overall response rate will be recorded as the percentage of patients with a CR or PR as best overall response.
Survival	12, 24, 36 and 48 weeks	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.