RHYTHM-I: Investigating Hypoxia in Rectal Tumours

NCT02157246 | Completed DMC

• 1 other identifier: OCTO_043
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypoxia in Rectal Cancer

Keywords

hypoxia; rectal cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Day -7 to -2 and day 10-12

Secondary Outcomes (4)

• Hypoxia gene microarray read outs from biopsies

  Day -7 to -2 (Group A & B) and day 10-12 (Group B)

• FMISO-PET SUVmax

  Day -7 to -2 (Group A & B) and 10-12 (Group B only)

• 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)

Other Outcomes (3)

• Blood sample

  Day -7 to -2 and day 10-12

• F-MISO PET hypoxic volumes and pCT images

  Prior to Day -7 (Group A)

• Radiotherapy planning feasibility study

  Day 10-12 (Group B)

Study Arms (2)

Group A, pimonidazole, no CRT

OTHER

Biopsy, Blood sample, F-MISO PET, pCT, functional MRI, Pimonidazole

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

Other: F-MISO PET; Other: pCT; Other: Functional MRI; Procedure: Biopsy; Procedure: Blood sample

Interventions

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

Group A, pimonidazole, no CRT; Group B, CRT

Blood sample PROCEDURE

Group A, pimonidazole, no CRT; Group B, CRT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Oxford University Hospitals NHS Trust

Oxford, OX3 7LE, United Kingdom

Location

MeSH Terms

Conditions

Hypoxia; Rectal Neoplasms

Interventions

pimonidazole; Biopsy; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Punctures

Study Officials

• Tim Maughan

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2013
• First Posted: June 5, 2014
• Study Start: October 1, 2013
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: March 13, 2017

Record last verified: 2017-03

Locations

GB (1)