Total Neoadjuvant Treatment Combined With Adaptive Radiotherapy for Rectal Cancer

Rectal Cancer Clinical Trial

— TNT-RECORD  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05883800
• Other study ID #: 402056
• Status: Recruiting
• Phase: N/A
• Start date: June 22, 2023
• Est. completion date: December 31, 2031

Study information

• Verified date: July 2023
• Source: Haukeland University Hospital
• Contact: Sara Pilskog, PhD
• Phone: 95890659
• Email: sara.margareta.cecilia.pilskog[@]helse-bergen.no
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 61
• Est. completion date: December 31, 2031
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

Radiation:
• On-couch adaptive radiotherapy
A new treatment plan, guided by volumetric images, is created at each treatment session

Locations

Country	Name	City	State
Norway	Haukeland University Hospital	Bergen

Sponsors (1)

Lead Sponsor	Collaborator
Haukeland University Hospital

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Bowel exposure	Radiation dose to bowel	Treatment week 1-2
Other	Immunogenic alterations from TNT	Presence of selected immune cells	Baseline and at surgery i.e. in treatment week 23-28
Other	Perfusion changes on MR	Changes in perfusion from contrast-enhanced MR	Baseline and at MR response evaluation up to week 25 of the study
Other	Diffusion changes on MR	Changes in diffusion from diffusion-weighted MR	Baseline and at MR response evaluation up to week 25 of the study
Other	Patient reported general outcome measures	Quality of life using EORTC qlq-c30 questionnaire	Baseline and up to 5 years of the study
Other	Patient reported colo-rectal outcome measures	Quality of life using EORTC qlq-cr29 questionnaire	Baseline and up to 5 years of the study
Other	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Overall survival	Overall survival from time of inclusion until death	Follow-up until 5 years or death
Secondary	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