Clinical trial NCT05877352: Intraoperative Electron Radiotherapy in Rectal Cancer - A Feasibility Trial
Official title: Intraoperative Electron Radiotherapy in Rectal Cancer - A Feasibility Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Locally Advanced Rectal Cancer
Locally Recurrent Rectal Cancer
Lead sponsor: University Hospital Southampton NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: IntraOp Medical Corporation
name: PLANETS Cancer Charity
name: Cancer Research UK
First posted: 2023-05-26
Enrollment: 31
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A single centre double-blinded three-arm randomised controlled trial of extended margin surgery + IOERT at standard dose (10 Gy) versus extended margin surgery + IOERT at higher dose (15 Gy) versus extended margin surgery alone (no IOERT) in a 1:1:1 ratio in patients with LARC or LRRC.
Primary purpose: TREATMENT

Brief summary: Single centre double-blinded three-arm randomised controlled trial of extended margin surgery + IOERT at standard dose (10 Gy) versus extended margin surgery + IOERT at higher dose (15 Gy) versus extended margin surgery alone in a 1:1:1 ratio in patients with Locally Advanced Rectal Cancer (LARC) or Locally Recurrent Rectal Cancer (LRRC).

Detailed description: Rectal cancer is a cancer that occurs in the pelvis from the rectum. Locally advanced rectal cancer outgrows the rectum and attaches to other body parts in the pelvis and locally recurrent rectal cancer is a rectal cancer that comes back after surgery, and usually attaches to many different pelvic structures. They are both difficult to manage. The standard of care treatment involves chemotherapy and radiotherapy, followed by what is known as an extended margin operation to remove all cancer affected organs and not leave any cancer cells behind. If cancer cells reach the edge of the removed tissue, there is a high chance of leaving cancer cells behind. This is a key predictor of negative outcome in patients. Intraoperative electron beam radiotherapy (IOERT) was developed to help improve patient outcomes. Once the cancer has been removed, the surgeon and a cancer radiotherapy specialist examine the patient's scans, the cancer specimen and the area the cancer was in, and if there is concern about small numbers of cancer cells being left behind they treat the area with radiotherapy to destroy these cells. Patients that are due to receive treatment for these subsets of rectal cancer will be approached to take part. If eligible on the day of surgery the patient will be randomised to one of three arms: Arm A - standard of care (No IOERT), Arm B - extended margin surgery plus IOERT (10 Gy), or Arm C - extended margin surgery plus higher dose IOERT (15 Gy). The surgeon, cancer specialist team and patient will be blinded to study treatment. Patients will be followed up at 30 days, 3 months and for a minimum of 12 months post surgery as part of the trial and they will be followed up for 5 years as part of standard care.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 16
* Non-metastatic/oligo-metastatic (up to 3 lesions from 2 sites predicted to be radically treatable) - locally advanced or locally recurrent disease involving the posterior or lateral components of the pelvis and predicted to be resectable but with close margins from imaging as determined by a specialist MDT (sMDT)
* Colorectal sMDT review with experience in pelvic exenteration, which has proposed IntrOperative Electron Radiotherapy (IOERT) as an option for treatment
* Patient suitable for IOERT as component of treatment in the view of the responsible Clinical Oncologist
* Performance status ≤1 as defined by the Eastern Cooperative Oncology Group (ECOG)
* Deemed medically fit for surgery
* Written informed consent

Exclusion Criteria:

* Unresectable disease/likelihood of R2 resection
* sMDT determined excess prior radiotherapy within IOERT target zone
* Women who are pregnant or breastfeeding
* Participation within an interventional clinical trial within 3 months of the point of registration within ELECTRA

Primary outcomes:
measure: Patients meeting eligibility criteria
timeFrame: 2 years
measure: Patients accepting randomisation
timeFrame: 2 years
measure: Successful delivery of IOERT
timeFrame: 2 years
measure: Blind maintained for patients and clinicians
timeFrame: 2 years
measure: Questionnaire analysis
timeFrame: 2 years
measure: Availability of potential primary outcome data
timeFrame: 2 years
Secondary outcomes:
measure: Morbidity
timeFrame: Up to 30 days post randomisation
measure: Mortality
timeFrame: 30 days post randomisation
measure: IOERT Field Recurrence
timeFrame: 12 months post randomisation
measure: Overall local recurrence
timeFrame: 12 months post randomisation
measure: Overall survival
timeFrame: 12 months post randomisation
measure: Treatment related toxicity
timeFrame: 12 months post randomisation
measure: Time to local or systemic recurrence
timeFrame: Time from randomisation to local or systemic recurrence or 3 years post the start of recruitment, whichever comes first
measure: R1 Rate
timeFrame: At randomisation
measure: EQ-5D-5L
timeFrame: At 3 and 12 months post randomisation
measure: LRRC QoL
timeFrame: At 3 and 12 months post randomisation
measure: QLQ-C30
timeFrame: At 3 and 12 months post randomisation
measure: SF-36
timeFrame: At 3 and 12 months post randomisation
measure: Resource use and cost
timeFrame: At 3 and 12 months post randomisation
Other outcomes:
Locations:
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
state: Hampshire
Study officials:
affiliation: University Hospital Southampton NHS Foundation Trust
name: Alex Mirnezami, Prof
role: PRINCIPAL_INVESTIGATOR
References: