RHYTHM-I: Investigating Hypoxia in Rectal Tumours

Not Applicable

Completed

• Conditions: Hypoxia in Rectal Cancer
• Interventions: Other: F-MISO PET; Other: Pimonidazole; Other: pCT; Procedure: Biopsy; Other: Functional MRI; Procedure: Blood sample

• Registration Number: NCT02157246
• Lead Sponsor: University of Oxford

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-10
• Study First Submitted: 2013-10-10
• Study First Submitted QC: 2014-06-03
• Study First Posted: 2014-06-05
• Primary Completion: 2016-11
• Study Completion: 2016-11
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-08
• Last Update Posted: 2017-03-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group B, CRT	pCT	Biopsy, Blood sample, F-MISO PET, pCT, functional MRI
Group B, CRT	Biopsy	Biopsy, Blood sample, F-MISO PET, pCT, functional MRI
Group A, pimonidazole, no CRT	pCT	Biopsy, Blood sample, F-MISO PET, pCT, functional MRI, Pimonidazole
Group A, pimonidazole, no CRT	Biopsy	Biopsy, Blood sample, F-MISO PET, pCT, functional MRI, Pimonidazole
Group B, CRT	F-MISO PET	Biopsy, Blood sample, F-MISO PET, pCT, functional MRI
Group B, CRT	Blood sample	Biopsy, Blood sample, F-MISO PET, pCT, functional MRI
Group A, pimonidazole, no CRT	Functional MRI	Biopsy, Blood sample, F-MISO PET, pCT, functional MRI, Pimonidazole
Group A, pimonidazole, no CRT	Blood sample	Biopsy, Blood sample, F-MISO PET, pCT, functional MRI, Pimonidazole
Group A, pimonidazole, no CRT	Pimonidazole	Biopsy, Blood sample, F-MISO PET, pCT, functional MRI, Pimonidazole
Group A, pimonidazole, no CRT	F-MISO PET	Biopsy, Blood sample, F-MISO PET, pCT, functional MRI, Pimonidazole
Group B, CRT	Functional MRI	Biopsy, Blood sample, F-MISO PET, pCT, functional MRI

Primary Outcome Measures

Name	Time	Method
Group A FMISO-PET derived hypoxic volumes	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	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 Outcome Measures

Name	Time	Method
FMISO-PET SUVmax	Day -7 to -2 (Group A & B) and 10-12 (Group B only)	Group A: Assess inter-individual variability in FMISO uptake and intra-individual reproducibility of FMISO-PET in rectal cancer.; Group B: Determine correlation of baseline and day 10-12 FMISO-PET SUVmax with radiological/pathological response, immunohistochemical and genetic markers of hypoxia and other factors affecting response to radiotherapy following CRT.
Hypoxia gene microarray read outs from biopsies	Day -7 to -2 (Group A & B) and day 10-12 (Group B)	Group A: To assess if F-MISO PET defined hypoxia correlates with hypoxia metagene expression.; Group B: To assess if baseline measures of hypoxia and the presence of tumour hypoxia after 8-10 fractions of CRT correlate with radiological/pathological response.
pCT derived blood flow parameters	Day -7 to -2 (Group A & B) and day 10-12 (Group B)	Group A: Assess inter-individual variability in pCT derived blood flow parameters and intra-individual reproducibility of pCT in rectal cancer. Assessment of the utility of pCT derived AIF in the processing of dynamic FMISO-PET scans.; Group B: Quantitative changes in pCT derived blood flow parameters after 8-10 fractions of CRT.
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)	Group A: Comparison of changes in T1/T2\* MRI before and after supplemental oxygen breathing.; Group B: Changes in native T1/T2\* MRI from baseline and before and after supplemental oxygen breathing.

Trial Locations

Locations (1)

Oxford University Hospitals NHS Trust; 🇬🇧 Oxford, United Kingdom