Clinical trial NCT01539824: A Study of IMM-101 in Combination With Radiation Induced Tumour Necrosis in Colorectal Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Immodulon Therapeutics Ltd
Sponsor class: INDUSTRY
First posted: 2012-02-28
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria:

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.

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.

Primary outcomes:
measure: Disease Stabilisation Rate
timeFrame: 24 weeks
Secondary outcomes:
measure: Safety and Tolerability Profiles
timeFrame: 48 weeks
measure: Objective Response Rate
timeFrame: 12, 24, 36 and 48 weeks
measure: Disease Stabilisation Rate
timeFrame: 12, 36 and 48 weeks
measure: Overall Disease Stabilisation Rate
timeFrame: 12, 36 and 48 weeks.
measure: Overall Response Rate
timeFrame: 12, 24, 36 and 48 weeks.
measure: Survival
timeFrame: 12, 24, 36 and 48 weeks
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: HCA International, The Sarah Cannon Research Institute
city: London
country: United Kingdom
facility: The London Clinic
Study officials:
affiliation: Leaders In Oncology Care, Harley St, London
name: Andrew Gaya
role: PRINCIPAL_INVESTIGATOR
References: