Total Neoadjuvant Treatment Combined With Adaptive Radiotherapy for Rectal Cancer (TNT-RECORD)

TNT-RECORD:Total Neoadjuvant Treatment in Rectal Cancer With On-couch Adaptive Radiotherapy

Diarrhea was the most frequently reported severe adverse event in the treatment regime of pre-operative sequential short-course radiotherapy followed by chemotherapy (so called total neo-adjuvant treatment).

This study therefore investigates the benefit of on-couch adaptation for locally advanced rectal cancer patients undergoing this treatment regime.

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Radiation: On-couch adaptive radiotherapy

Detailed Description

This is a prospective single-arm study investigating the benefit of on-couch adaptation for locally advanced rectal cancer patients prescribed with pre-operative sequential short-course radiotherapy (RT) followed by Oxaliplatin-combined chemotherapy (mFOLFOX(6) or CAPOX). On-couch adaptation, where the radiation dose is tailored to the anatomy of the patient at each radiotherapy session. Firstly, the study will investigate if on-couch adaptation result in less gastro-intestinal adverse events, secondly it will reveal if this possible reduction lead to more patients being able to fulfill all cycles of prescribed chemotherapy.

• Study Type: Interventional
• Enrollment (Estimated): 61
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sara Pilskog, PhD; Phone Number: 0047 95890659; Email: sara.margareta.cecilia.pilskog@helse-bergen.no
• Study Contact Backup: Name: Unn Hege Lilleøren, MD; Phone Number: 0047 92054547; Email: unn.hege.lilleoren@helse-bergen.no

Study Locations

• Norway
  • Bergen, Norway, 5021
    • Recruiting
    • Haukeland University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with loco-regional advanced rectal adenocarcinoma with clinical indications for short-course with TNT chemotherapy i.e. having at least one of the following T4a, CRM+ (≤1 mm), N1c, N2 or extramural vascular invasion (EMVI+). Patients presenting at least one of these criteria in addition to involvement of the pelvic sidewall lymph nodes (PSW) can optionally be considered.
• ECOG status ≤ 1
• Being willing and able to give full written consent for participation

Exclusion Criteria:

• Previous rectal cancer treatment
• Previous irradiation to the treatment area e.g. prostate cancer
• Hip prosthesis
• Contraindications to MRI
• Pregnancy
• Abnormal DPYD genotype
• Known contraindication to 5-FU, Capecitabine or Oxaliplatin as judged by the investigators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Intervention: daily on-couch adaptive radiotherapy	Radiation: On-couch adaptive radiotherapy; A new treatment plan, guided by volumetric images, is created at each treatment session; Other Names: online ART

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of acute gastro-intestinal toxicity equal or higher than grade 2	Incidence of acute gastro-intestinal toxicity from therapy graded according to CTCAE ver. 5.	Up to administration of the last course of chemotherapy or week 22, whichever comes first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with disease related treatment failure	Disease-related treatment failure include the first of any of the following events: (i) During treatment: Non-radical resection of primary tumor (R2 resection) or un-fit of for surgery due to progression, death from treatment (ii) During, or after treatment: Loco-regional recurrence (including regrowth after potential watch-and-wait), distant metastasis (including M re-staging at surgery), death from rectal cancer, second primary rectal cancer.	5 years after surgery
Number of patients with pathological complete response (pCR)	pCR after completion of the intended or tolerated TNT	At surgery i.e. in treatment week 23-28
Tumour regression grade	Radiological based clinical response evaluation on MR (mrTRG)	Baseline to response evaluation on MR in up to week 25 of the study
Overall survival	Overall survival from time of inclusion until death	Follow-up until 5 years or death
Incidence of late gastro-intestinal toxicity equal or higher than grade 2	Incidence of late gastro-intestinal events (e.g.diarrhea, rectal hemorrhage, rectal and/or abdominal pain) from therapy graded according to CTCAE ver. 5.	5 years
Number of participants that require alteration of chemotherapy due to toxicity	Alterations of chemotherapy, defined as dose-reduction or pre-maturely stopping chemotherapy administration	From treatment week 3 up to week 20

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bowel exposure	Radiation dose to bowel	Treatment week 1-2
Immunogenic alterations from TNT	Presence of selected immune cells	Baseline and at surgery i.e. in treatment week 23-28
Perfusion changes on MR	Changes in perfusion from contrast-enhanced MR	Baseline and at MR response evaluation up to week 25 of the study
Diffusion changes on MR	Changes in diffusion from diffusion-weighted MR	Baseline and at MR response evaluation up to week 25 of the study
Patient reported general outcome measures	Quality of life using EORTC qlq-c30 questionnaire	Baseline and up to 5 years of the study
Patient reported colo-rectal outcome measures	Quality of life using EORTC qlq-cr29 questionnaire	Baseline and up to 5 years of the study
Patient reported bowel-related outcome measures	Quality of life using low anterior resection syndrome (LARS) score	Baseline and up to 5 years of the study

Collaborators and Investigators

• Sponsor: Haukeland University Hospital
• Investigators: Principal Investigator: Unn Hege Lilleøren, MD, Dept. of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: February 24, 2023
• First Submitted That Met QC Criteria: May 22, 2023
• First Posted (Actual): June 1, 2023

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: 402056

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No