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.
Metastatic Colorectal Cancer
Biological: Mycobacterium obuense
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- Disease stabilisation rate [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]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.
- safety and tolerability profiles [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
No clinically relevant deleterious effect of IMM-101 on 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 will be monitored through the study by a Data Monitoring Committee (DMC)
- Objective response rate [ Time Frame: 12, 24, 36 and 48 weeks ] [ Designated as safety issue: No ]
- Disease stabilisation rate [ Time Frame: 12, 36 and 48 weeks ] [ Designated as safety issue: No ]
- Overall disease stabilisation rate [ Time Frame: End of study ] [ Designated as safety issue: No ]
- Overall response rate [ Time Frame: End of study ] [ Designated as safety issue: No ]
- Progression-free survival [ Time Frame: 12, 24, 36 and 48 weeks ] [ Designated as safety issue: No ]
- Survival [ Time Frame: 12, 24, 36 and 48 weeks ] [ Designated as safety issue: No ]
- Tumour Markers [ Time Frame: 12, 24, 36 and 48 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||February 2012|
|Estimated Study Completion Date:||August 2014|
|Estimated Primary Completion Date:||February 2013 (Final data collection date for primary outcome measure)|
|Experimental: IMM-101 plus SBRT||
Biological: Mycobacterium obuense
IMM-101 is a suspension of heat-killed whole cell M. obuense in borate-buffered saline.
Other Name: IMM-101Radiation: SBRT
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.
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.
|Contact: Andrew Gaya||+44 (0) 20 7317 email@example.com|
|Contact: Laura Moriatyfirstname.lastname@example.org|
|The London Clinic||Recruiting|
|London, United Kingdom|
|Contact: Andrew Gaya 44 (0) 20 7317 2661 / email@example.com|
|Principal Investigator: Andrew Gaya|
|HCA International, The Sarah Cannon Research Institute||Recruiting|
|London, United Kingdom, W1G 6AD|
|Contact: Hendrik-Tobias Arkenau 020 32195200 firstname.lastname@example.org|
|Principal Investigator: Hendrik-Tobias Arkenau|
|Principal Investigator:||Andrew Gaya||Leaders In Oncology Care, Harley St, London|