Title

RHYTHM-I

Chief Investigator: 

Sponsor: University of Oxford
Funded by: CRUK EPSRC Oxford Cancer Imaging Centre

RHYTHM-I: modulation of Radiotherapy according to HYpoxia: exploiting changes in the Tumour Microenvironment to improve outcome in rectal cancer

Study Status

Closed to recruitment

Many thanks to the trial team at the Churchill Hospital for their efforts during the trial.

This is a single-centre study at the Churchill Hospital, Oxford.

Target recruitment: 15 patients (5 in Group A and 10 in Group B)

Final recruitment: 14 patients; 3 in Group A, 11 in Group B (May 2016)

Primary Objectives

Group A:

To assess the utility of FMISO-PET imaging in quantifying and defining the spatial deistribution of hypoxic regions within rectal cancers.

Group B:

Can changes in tumour hypoxia and perfusion be seen after 8-10 fractions of CRT?

Study Schema

Inclusion Criteria

Group A (Inclusion)

  1. 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).
  2. The tumour on MRI and/or CT measures at least 2 cm by 2 cm.
  3. MRI confirmation that the circumferential resection margin is not involved or threatened
  4. Agreement from the local multi-disciplinary team (MDT) that the tumour is operable and does not require pre-operative CRT.
  5. The patient is medically fit for operative resection of the tumour.
  6. Male or female, Age ≥ 18 years.
  7. ECOG performance score of 0-2 and be capable of co-operating with protocol.
  8. Written (signed and dated) informed consent.
  9. Haematological and biochemical indices within the ranges shown below:
Lab Test Value required
Haemoglobin (Hb) ≥12.0 g/dL
Platelet count ≥ 100 x 109/L
PT 10-14 seconds

Renal function: Serum Creatinine

Or Calculated GFR

<120 mmol/L

>50 ml/min

Group B (Inclusion)

  1. Histologically confirmed invasive adenocarcinoma of the rectum
     
  2. Pelvic MRI defined disease:

(A) Mesorectal fascia (MRF) involved or breached

  • Includes involvement of adjacent organ

(B) Mesorectal fascia threatened (tumour ≤ 1mm from MRF). This includes:

  • Primary tumour ≤ 1mm from MRF
  • Extramural vascular invasion ≤ 1mm from MRF
  • Tumour deposit with irregular border and mixed signal intensity ≤ 1mm from MRF

(C) Low tumours at/below the level of the levators where:

  • Tumour ≤ 1mm from levator on two imaging planes
  • Tumour through full thickness of muscularis propria or beyond at level of puborectalis sling or below
  • Tumour involving the intersphincteric plane
  • Tumour involving the external anal sphincter
  1. Patient is considered likely to be fit for surgical resection following CRT
  2. Patient has been considered to be medically fit to receive CRT by their treating oncologist
  3. Male or female, Age  18 years.
  4. ECOG performance score of 0-2 (see Appendix 1).
  5. The patient is willing and able to give informed consent and to comply with the protocol for the duration of the study.
  6. Haematological and biochemical indices within the ranges shown below:
Lab Test Value required
Haemoglobin (Hb) ≥12.0 g/dL
Absolute neutrophil count ≥ 1.5 x 109/L
Platelet count ≥ 100 x 109/L
PT 10-14 seconds

Renal function: Serum Creatinine

Or Calculated GFR

<120 mmol/L

>50 ml/min

Exclusion Criteria

Group A (Exclusion)

  1. Unequivocal evidence of metastatic disease.  Patients with equivocal lesions will be determined as eligible on consensus of the MDT.
  2. Previous pelvic radiotherapy.
  3. Pregnant or breast-feeding women, or women of childbearing potential unless effective methods of contraception are used.
  4. Treatment with any other investigational agent, or participation in another interventional clinical trial within 28 days prior to enrolment.
  5. Currently taking anti-coagulants
  6. 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.
  7. Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV.

Group B (Exclusion)

  1. Previous pelvic radiotherapy (including brachytherapy)
  2. Unequivocal evidence of metastatic disease.  Patients with equivocal lesions will be determined as eligible on consensus of the MDT.
  3.  Pregnant or breast-feeding women, or women of childbearing potential unless effective methods of contraception are used.
  4. Currently taking anti-coagulants
  5.  Gastrointestinal disorder which would interfere with oral therapy and its bioavailability
  6.  Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment.
  7. 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
  8. 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.
  9. Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV.

Groups A and B: Optional supplemental oxygen breathing with T1/T2* MRI (Exclusion)

  • Ongoing supplemental oxygen as part of clinical care
  • Known lung disease with carbon dioxide retention
  • Chronic obstructive airways disease with known or at risk 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.

Key Dates

Recruitment Completed: 30 Apr 2016

Trial completion date: 22 Nov 2016

Data Submission

Data submission for this trial is via electronic submission of data in OpenClinica.

OpenClinica Training

OpenClinica is the world's leading open source clinical trial software for electronic data capture and clinical data management. 

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