RHYTHM-I: Modulation of Radiotherapy According to HYpoxia: Exploiting Changes in the Tumour Microenvironment to Improve Outcome in Rectal Cancer.
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Hypoxia in Rectal Cancer
- Sponsor
- University of Oxford
- Enrollment
- 14
- Locations
- 1
- Primary Endpoint
- Group A FMISO-PET derived hypoxic volumes
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
A low level of oxygen in cancer cells makes them less likely to respond to chemotherapy and radiotherapy treatments. There is interest in using new drugs that improve the level of oxygen in tumours. Another approach would be to increase the radiotherapy dose to tumours with low oxygen levels.
Before we can do this for patients with rectal cancer, we need to develop a reliable way of identifying areas of low oxygen within the rectal tumour. This will make us able to tell which patients may be suitable for such a change in their treatment.
Traditionally, the level of oxygen in tumours is measured by inserting a needle into the tumour and measuring it directly. This is not possible in rectal cancer. This study has been designed to identify the best alternative method. We would like to do a blood test, take samples of cancer tissue and some detailed scans (18F-fluoromisonidazole (F-MISO) positron emission tomography, perfusion computed tomography, functional magnetic resonance imaging). The results of these tests will be compared to decide which gives us the most comprehensive and reliable information.
Patients in Group A go straight to surgery. By looking for markers of low oxygen levels on the tumour that has been removed, we will be able to find out which of the study tests performed before the tumour was removed is the best. By repeating the scans we will be able to see how reliable they are and how much they change on a day to day basis. We think that tumours that still have low levels of oxygen after 8 to 10 doses of radiotherapy are the least likely to respond to treatment.
Group B will have scans before radiotherapy treatment and after 8 to 10 doses of radiotherapy to see if we can identify the patients that have persistent low levels of oxygen.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Group A FMISO-PET derived hypoxic volumes
Time Frame: At surgery
Validation of FMISO-PET as a measure of hypoxia in rectal cancer. FMISO-PET derived hypoxic volumes will be compared to reconstructed volumes from the immunohistochemistry of PIMO, CAIX and HIF on whole mount histology of the resected tumour. The spatial distribution of FMISO uptake on PET images will be compared with PIMO, CAIX and HIF immunohistochemistry distributions in the resected tumour.
Group B Percentage change in FMISO-PET SUVmax and uptake volume
Time Frame: Day -7 to -2 and day 10-12
Quantifying the percentage change in FMISO SUVmax and uptake volume between the two FMISO-PET scans after 8-10 fractions of CRT.
Secondary Outcomes
- FMISO-PET SUVmax(Day -7 to -2 (Group A & B) and 10-12 (Group B only))
- Hypoxia gene microarray read outs from biopsies(Day -7 to -2 (Group A & B) and day 10-12 (Group B))
- pCT derived blood flow parameters(Day -7 to -2 (Group A & B) and day 10-12 (Group B))
- Comparison of changes in T1/T2* MRI(Prior to Day -7 (Group A), Day -21 to Day -1 (Group B), Day 10-12 (Group B))