A feasibility trial to evaluate the use of an an imaging biomarker called magnetic resonance tumour regression grade (mrTRG) to identify and manage good and poor responders to chemoradiotherapy for use in patients with rectal (bowel) cancer.

• Register: EUCTR
• Last refreshed on: 25 April 2016
• Main ID: EUCTR2015-003009-40-GB
• Date of registration: 13/10/2015
• Prospective Registration: Yes
• Primary sponsor: Royal Marsden NHS Foundation Trust
• Public title: A feasibility trial to evaluate the use of an an imaging biomarker called magnetic resonance tumour regression grade (mrTRG) to identify and manage good and poor responders to chemoradiotherapy for use in patients with rectal (bowel) cancer.
• Scientific title: Magnetic Resonance Tumour Regression Grade (mrTRG) as a Novel Biomarker to Stratify Management of Good And Poor Responders To Chemoradiotherapy: A Rectal Cancer Multicentre Randomised Control Trial - TRIGGER Trial Version 1.0
• Date of first enrolment: 18/12/2015
• Target sample size: 90
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003009-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Standard of care - surgery and adjuvant chemotherapy Number of treatment arms in the trial: 2

Countries of recruitment

Brazil, Canada, Cyprus, Italy, United Kingdom, United States

Contacts

• Name: Michelle Frost
• Affiliation: Royal Marsden NHS Foundation Trust

• Name: Michelle Frost
• Affiliation: Royal Marsden NHS Foundation Trust

Key inclusion & exclusion criteria

Inclusion criteria:
1) Have a biopsy-confirmed adenocarcinoma 0-15cm from the anal verge (on MRI or rigid sigmoidoscopy)
2) Have locally Advanced Rectal Carcinoma diagnosed by MRI (mrCRM unsafe or =mrT3c [>5mm beyond muscularis propria] or mrEMVI positive disease)
3) Be deemed to require chemoradiotherapy
4) Scheduled to receive 45Gy - 55Gy long course radiotherapy
5) Be aged 18 years or over.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 45

Exclusion criteria:
1) Have metastatic disease (including resectable liver metastases)
2) Are contraindicated for MRI eg. non-mr compatable hip prosthesis, cardiac pacemaker
3) Are scheduled to receive less than 45Gy or more than 55Gy long course radiotherapy
4) Are contraindicated for chemoradiotherapy (CRT) or systemic chemotherapy
5) Are receiving or planned to receive treatment outside of that stipulated by the protocol,such as an alternative cytotoxic or investigational drug.
6) Are pregnant, breastfeeding or unable / unwilling to comply with pregnancy prevention guidelines
7) Any other malignant disease within the preceding 5 years with the exception of non- melanomatous skin cancer, carcinoma in situ and early stage disease with <5% recurrence risk



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Rectal cancer
MedDRA version: 18.0 Level: PT Classification code 10061758 Term: Chemotherapy System Organ Class: 10042613 - Surgical and medical procedures
MedDRA version: 18.0 Level: PT Classification code 10061451 Term: Colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 18.0 Level: PT Classification code 10068093 Term: Gastrointestinal surgery System Organ Class: 10042613 - Surgical and medical procedures

Intervention(s)

Product Name: Capecitabine
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Capecitabine 150mg film coated tablets
CAS Number: 154361-50-9
Other descriptive name: CAPOX Regimen (if combined with Oxaliplatin given on day 1 of each 3 weekly cycle)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150mg tablets-
INN or Proposed INN: Capecitabine 500mg film coated tablets
CAS Number: 154361-50-9
Other descriptive name: CAPOX regimen (if combined with Oxaliplatin)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500mg tablets-

Trade Name: 5-fluorouracil
Product Name: 5-fluorouracil
Pharmaceutical Form: Infusion
INN or Proposed INN: 5-fluorouracil
CAS Number: 51-21-8
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25mg/ml-
INN or Proposed INN: 5-fluorouracil
CAS Number: 51-21-8
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50mg/ml-

Trade Name: Oxaliplatin
Product Name: Oxaliplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Oxaliplatin
CAS Number: 63121-00-6
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Trade Name: Sodiofolin
Product Name: folinic acid/calcium folinate
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Folinic acid
CAS Number: 1492-18-8
Other descriptive name: calcium folinate
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Main Objective: A trial for patients with rectal cancers that require chemotherapy and radiotherapy (CRT) before surgery. The trial investigates whether the MRIs that are already performed can be used in a smarter way to give a better idea of whether the tumour has responded to the chemotherapy and radiotherapy.

In the control arm patients will follow best current practice. In the intervention arm treatment will be tailored according to CRT response assessed using MRI. The good response group will be offered deferral of surgery (non operative management). The poor response group will be offered a change in the timing of chemotherapy, as we believe that offering half of the chemotherapy prior to surgery will shrink the tumour further and increase the likelihood of complete surgical removal.

The principal objective of this feasibility trial is to assess patient recruitment rate.

Once 90 patients have been recruited we intend to proceed to a planned larger Phase III trial of approximately 630

Secondary Objective: 1) to evaluate the safety of the MRI-directed management approach by comparing the incidence of incomplete surgical removal of the cancer between groups. The rate of inoperable growth in patients managed by deferral of surgery will also be considered.

2) to evaluate toxicity and morbidity - we will compare the number and severity of complications relating to surgery and chemotherapy.

3) to assess quality of life

4) to evaluate the agreement and reproducibility of measurements of magnetic resonance tumour regression grade (mrTRG) by the recruiting radiologists (please note a site will not be able to open until the allocated radiologist has demonstrated they can perform MRI scans according to a published protocol and, for measurements of mrTRG, achieve a high Kappa agreement of 0.7 or more).

Timepoint(s) of evaluation of this end point: 10 months from start of patient recruitment

Primary end point(s): Total number of patients randomised per month during the last 4 months of recruitment

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: pCRM rate - at time of surgery
Strength of agreement mrTRG - site initiation and end of recruitment period of feasibility trial.
Acute toxicity - at time of chemotherapy
Surgical morbidity - 30 days and 12 months post surgery
Quality of surgery - at time of surgery when histopathology analysis performed

Secondary end point(s): • The pCRM rate will be compared between the control and investigation arms.
• The strength of agreement of the reported mrTRG will be evaluated between the site radiologist versus the central radiologist at site initiation and at the end of the recruitment phase of feasibility trial.
• Acute toxicity will be recorded to CTCAE v4.0 protocol. The grade 3- 5 adverse events will be compared between the control and intervention arms on an intention to treat basis.
• Early (30 day) and late (up to 12 months) surgical morbidity will be reported according to the Clavien-Dindo classification
• Quality of surgery will be determined by using the mesorectal grading system and a similar system will be used for grading the quality of APE specimens

Secondary ID(s)

CCR4326

Source(s) of Monetary Support

Pelican Cancer Foundation