A Study of IMM-101 in Combination With Radiation Induced Tumour Necrosis in Colorectal Cancer
A Study of IMM-101 in Combination With Radiation Induced Tumour Necrosis in 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.
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.
Patients are eligible to be included in the study if they:

 Are male or female; aged ≥ 18 years. Have a histologically confirmed colorectal
 adenocarcinoma. Have documented evidence of disease progression following at least one line
 of chemotherapy.

 Have no further standard chemotherapy options available have refused further chemotherapy.

 Have metastatic lesions in at least two sites in the liver (+/- other sites) suitable for
 bidimensional and volumetric evaluation by CT scan.

 Have WHO performance status of 0-2. Have a Cockcroft calculated Glomerular Filtration Rate
 of > 40mL/min at screening.

 Have a life expectancy, in the opinion of the Investigator, of > 3 months from screening.

 Patients are not eligible if one or more of the following statements are applicable:

 Patient has evidence of central nervous system metastasis. Patient has severe, active
 uncontrolled infection requiring systemic antibiotics, antiviral or antifungal treatments.

 Patient has 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.

 Patient has serum albumin < 30 g/L at screening. Patient has a C-reactive protein (CRP) >
 70 mg/L at screening. Patient has transaminases (ALT or AST) > 5 X Upper Limit of Normal at
 screening.

 Patient has a bilirubin level > 2 X Upper Limit of Normal at screening. Patient has had
 radiotherapy in the 12 weeks before screening. Patient has used depot corticosteroids in
 the 6 weeks before screening. Patient has had 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.

 Patient of child-bearing potential who is not using an approved method of birth control
 (e.g., physical barrier [patient and partner], contraceptive pill or patch, spermicide and
 barrier, or intrauterine device [IUD]). Those patients that utilise hormonal contraceptives
 must have used the same method for at least three months before study dosing. Patients of
 non-child-bearing potential are defined as having 12 month amenorrhoea or are surgically
 sterile.

 Patient who is pregnant, breast feeding or planning a pregnancy during the course of the
 study. Where appropriate, a pre-treatment serum pregnancy test measuring human chorionic
 gonadotrophin (hCG) must be negative.

 Patient has been administered any investigational product in the 3 months before screening.

 Contraindication to CT scan, e.g., allergy to iodine based contrast medium. Patient has 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.

 Patient has presence of any uncontrolled concomitant disease (e.g., unstable angina
 pectoris, congestive heart failure, myocardial infarction, cardiac arrhythmias,
 uncontrolled severe hypertension) which, in the judgement of the Investigator, might
 interfere with the activity of IMM-101, or with the performance of this study.

 Patient has a history of serious adverse reaction or serious hypersensitivity to any drug
 that in the opinion of the Investigator may raise a safety concern.

 Patient has had any previous treatment with IMM-101 or related mycobacterial immunotherapy
 (prior BCG vaccination against TB is allowed).

 Patient is known to have a history of human immunodeficiency virus (HIV) or syphilis,
 current symptomatic Hepatitis B or C.

 Patient is unable or unwilling to comply with the protocol.