Hypoxia in Rectal CancerRHYTHM-INCT02157246
RHYTHM-I: Investigating Hypoxia in Rectal Tumours
A study testing Pimonidazole, F-MISO PET and pCT in people with Hypoxia in Rectal Cancer, run by University of Oxford at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypoxia in Rectal Cancer
- What is being tested?
- Pimonidazole, F-MISO PET and pCT
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2013to Nov 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- T2-3 N0 histologically proven adenocarcinoma of the rectum (if the MDT has an index of suspicion of malignancy high enough to proceed to surgical resection despite repeatedly non-diagnostic biopsies, the patient should be considered eligible).
- The tumour on MRI and/or CT measures at least 2 cm by 2 cm.
- MRI confirmation that the circumferential resection margin is not involved or threatened
- Agreement from the local multi-disciplinary team (MDT) that the tumour is operable and does not require pre-operative CRT.
- The patient is medically fit for operative resection of the tumour.
- Male or female, Age at least 18 years.
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- ECOG performance score of 0-2 and be capable of co-operating with protocol.
- Written (signed and dated) informed consent.
- Haematological and biochemical indices within the ranges shown below:
- Haemoglobin (Hb) ≥12.0 g/dL
- Platelet count ≥ 100 x 109/L
- PT 10-14 seconds
- Renal function:
- Serum Creatinine <120 mmol/L OR Calculated GFR >50 ml/min
- Histologically confirmed invasive adenocarcinoma of the rectum
- Pelvic MRI defined disease:
- Mesorectal fascia (MRF) involved or breached i. Includes involvement of adjacent organ b. Mesorectal fascia threatened (tumour ≤ 1mm from MRF). This includes i. Primary tumour ≤ 1mm from MRF ii. Extramural vascular invasion ≤ 1mm from MRF iii. Tumour deposit with irregular border and mixed signal intensity ≤ 1mm from MRF c. Low tumours at/below the level of the levators where: i. Tumour ≤ 1mm from levator on two imaging planes ii. Tumour through full thickness of muscularis propria or beyond at level of puborectalis sling or below iii. Tumour involving the intersphincteric plane iv. Tumour involving the external anal sphincter
- Patient is considered likely to be fit for surgical resection following CRT
- Patient has been considered to be medically fit to receive CRT by their treating oncologist
- Male or female, Age at least 18 years.
- ECOG performance score of 0-2.
- The patient is willing and able to give informed consent and to comply with the protocol for the duration of the study.
- Haematological and biochemical indices within the ranges shown below:
- Haemoglobin (Hb) ≥12.0 g/dL
- Absolute neutrophil count ≥1.5 x 10^9/L
- Platelet count ≥ 100 x 109/L
- PT 10-14 seconds
- Renal function:
- Serum Creatinine <120 mmol/L OR Calculated GFR >50 ml/min
Who cannot join
- Unequivocal evidence of metastatic disease. Patients with equivocal lesions will be determined as eligible on consensus of the MDT.
- Previous pelvic radiotherapy.
- Pregnant or breast-feeding women, or women of childbearing potential unless effective methods of contraception are used.
- Treatment with any other investigational agent, or participation in another interventional clinical trial within 28 days prior to enrolment.
- Currently taking anti-coagulants
- Patients who for any reason are unable to undergo MRI and/or CT scans as per local guidelines e.g. if they are fitted with a pacemaker, have metal fragments in or around the eye, cannot tolerate the scan for any reason or are allergic to contrast agents.
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- Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV.
- Previous pelvic radiotherapy (including brachytherapy)
- Unequivocal evidence of metastatic disease. Patients with equivocal lesions will be determined as eligible on consensus of the MDT.
- Pregnant or breast-feeding women, or women of childbearing potential unless effective methods of contraception are used.
- Currently taking anti-coagulants
- Gastrointestinal disorder which would interfere with oral therapy and its bioavailability
- Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment.
- Other psychological, social or medical condition, physical examination finding or a laboratory abnormality that the Investigator considers would make the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results.
- Patients who for any reason are unable to undergo MRI and/or CT scans as per local guidelines e.g. they are fitted with a pacemaker, have metal fragments in or around the eye, cannot tolerate the scan for any reason or are allergic to contrast agents.
- Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV.
- Exclusion Criteria (Optional supplemental oxygen breathing Groups A and B):
- Ongoing supplemental oxygen as part of clinical care
- Known lung disease with carbon dioxide retention
- Chronic obstructive airways disease with known or at risk of hypercapnia
- Most recent available arterial blood gas (ABG) from the current hospital admission demonstrates hypoxia or hypercapnia on room air.
- Any patient not felt to be suitable for supplemental oxygen as considered by an appropriately trained clinician.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Oxford University Hospitals NHS Trust
Oxford, OX3 7LE
About this study
Official title: RHYTHM-I: Modulation of Radiotherapy According to HYpoxia: Exploiting Changes in the Tumour Microenvironment to Improve Outcome in Rectal Cancer.
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.
Read more
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.
- Conditions
- Hypoxia in Rectal Cancer
- Being tested
- Pimonidazole, F-MISO PET, pCT, Functional MRI, Biopsy
- Keywords
- hypoxia, rectal cancer
- Medical subject headings
- Hypoxia, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PimonidazoleOther
F-MISO PETOther
pCTOther
Functional MRIOther
BiopsyProcedure or surgery
Blood sampleProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Group A, pimonidazole, no CRT | Other | Biopsy, Blood sample, F-MISO PET, pCT, functional MRI, Pimonidazole Receives: Other: Pimonidazole; Other: F-MISO PET; Other: pCT; Other: Functional MRI; Procedure: Biopsy; Procedure: Blood sample |
| Group B, CRT | Other | Biopsy, Blood sample, F-MISO PET, pCT, functional MRI Receives: Other: F-MISO PET; Other: pCT; Other: Functional MRI; Procedure: Biopsy; Procedure: Blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
Group A FMISO-PET derived hypoxic volumes
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.
Measured: At surgery
Group B Percentage change in FMISO-PET SUVmax and uptake volume
Quantifying the percentage change in FMISO SUVmax and uptake volume between the two FMISO-PET scans after 8-10 fractions of CRT.
Measured: Day -7 to -2 and day 10-12
Secondary outcomes (4)
Hypoxia gene microarray read outs from biopsies
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.
Measured: Day -7 to -2 (Group A & B) and day 10-12 (Group B)
FMISO-PET SUVmax
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.
Measured: Day -7 to -2 (Group A & B) and 10-12 (Group B only)
pCT derived blood flow parameters
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.
Measured: Day -7 to -2 (Group A & B) and day 10-12 (Group B)
Comparison of changes in T1/T2* MRI
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.
Measured: Prior to Day -7 (Group A), Day -21 to Day -1 (Group B), Day 10-12 (Group B)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2014 (estimated)
- Study startOct 2013
- Primary completionNov 2016
- Study completionNov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hypoxia in Rectal CancerStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tim Maughan, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02157246
- Sponsor's protocol ID
- OCTO_043
- Acronym
- RHYTHM-I
- Status last verified
- Mar 2017
- First submitted
- 10 Oct 2013
- Last updated
- 13 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RHYTHM-I: Modulation of Radiotherapy According to HYpoxia: Exploiting Changes in the Tumour Microenvironment to Improve Outcome in Rectal Cancer.
- ClinicalTrials.gov ID
- NCT02157246
- Acronym / sponsor ID
- RHYTHM-I / OCTO_043
- Conditions
- Hypoxia in Rectal Cancer
- Keywords
- hypoxia, rectal cancer
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- Oct 2013
- Primary completion
- Nov 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 5 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A, pimonidazole, no CRT | Other | Other: Pimonidazole, Other: F-MISO PET, Other: pCT, Other: Functional MRI, Procedure: Biopsy, Procedure: Blood sampleBiopsy, Blood sample, F-MISO PET, pCT, functional MRI, Pimonidazole |
| Group B, CRT | Other | Other: F-MISO PET, Other: pCT, Other: Functional MRI, Procedure: Biopsy, Procedure: Blood sampleBiopsy, Blood sample, F-MISO PET, pCT, functional MRI |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- T2-3 N0 histologically proven adenocarcinoma of the rectum (if the MDT has an index of suspicion of malignancy high enough to proceed to surgical resection despite repeatedly non-diagnostic biopsies, the patient should be considered eligible).
- The tumour on MRI and/or CT measures at least 2 cm by 2 cm.
- MRI confirmation that the circumferential resection margin is not involved or threatened
- Agreement from the local multi-disciplinary team (MDT) that the tumour is operable and does not require pre-operative CRT.
- The patient is medically fit for operative resection of the tumour.
Key exclusion criteria (22 listed)
- Unequivocal evidence of metastatic disease. Patients with equivocal lesions will be determined as eligible on consensus of the MDT.
- Previous pelvic radiotherapy.
- Pregnant or breast-feeding women, or women of childbearing potential unless effective methods of contraception are used.
- Treatment with any other investigational agent, or participation in another interventional clinical trial within 28 days prior to enrolment.
- Currently taking anti-coagulants
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pimonidazole | Other | Group A, pimonidazole, no CRT |
| F-MISO PET | Other | Group A, pimonidazole, no CRT, Group B, CRT |
| pCT | Other | Group A, pimonidazole, no CRT, Group B, CRT |
| Functional MRI | Other | Group A, pimonidazole, no CRT, Group B, CRT |
| Biopsy | Procedure or surgery | Group A, pimonidazole, no CRT, Group B, CRT |
| Blood sample | Procedure or surgery | Group A, pimonidazole, no CRT, Group B, CRT |
Primary outcome
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.
4 secondary outcomes
Hypoxia gene microarray read outs from biopsies
Time frame: Day -7 to -2 (Group A & B) and day 10-12 (Group B)
FMISO-PET SUVmax
Time frame: Day -7 to -2 (Group A & B) and 10-12 (Group B only)
pCT derived blood flow parameters
Time frame: Day -7 to -2 (Group A & B) and day 10-12 (Group B)
Comparison of changes in T1/T2* MRI
Time frame: Prior to Day -7 (Group A), Day -21 to Day -1 (Group B), Day 10-12 (Group B)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2017.
Related trials for Hypoxia in Rectal Cancer
RecruitingPhase 1
Papaverine in Combination With Radiation Therapy for the Treatment of Locally Advanced Rectal Cancer, DINOMITE Trial
Locally Advanced Rectal Adenocarcinoma, Stage II Rectal Cancer AJCC v8
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tim Maughan principal investigator
University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pimonidazole, F-MISO PET and pCT in people with Hypoxia in Rectal Cancer, run by University of Oxford at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 29 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Group A FMISO-PET derived hypoxic volumes (time frame: At surgery). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2017.