TNT-RECORD: Total Neoadjuvant Treatment Combined With Adaptive Radiotherapy for Rectal Cancer
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
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 Design
Arms and Interventions
| 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:
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Outcome Measures
Primary Outcome Measures
- Incidence of acute gastro-intestinal toxicity equal or higher than grade 2 [Up to administration of the last course of chemotherapy or week 22, whichever comes first]
Incidence of acute gastro-intestinal toxicity from therapy graded according to CTCAE ver. 5.
Secondary Outcome Measures
- Number of participants that require alteration of chemotherapy due to toxicity [From treatment week 3 up to week 20]
Alterations of chemotherapy, defined as dose-reduction or change of drugs
- Number of patients with disease related treatment failure [5 years after surgery]
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.
- Number of patients with pathological complete response (pCR) [At surgery i.e. in treatment week 23-28]
pCR after completion of the intended or tolerated TNT
- Tumour regression grade [Baseline to response evaluation on MR in up to week 25 of the study]
Radiological based clinical response evaluation on MR (mrTRG)
- Overall survival [Follow-up until 5 years or death]
Overall survival from time of inclusion until death
- Incidence of late gastro-intestinal toxicity equal or higher than grade 2 [5 years]
Incidence of late gastro-intestinal events (e.g.diarrhea, rectal hemorrhage, rectal and/or abdominal pain) from therapy graded according to CTCAE ver. 5.
Other Outcome Measures
- Bowel exposure [Treatment week 1-2]
Radiation dose to bowel
- Immunogenic alterations from TNT [Baseline and at surgery i.e. in treatment week 23-28]
Presence of selected immune cells
- Perfusion changes on MR [Baseline and at MR response evaluation up to week 25 of the study]
Changes in perfusion from contrast-enhanced MR
- Diffusion changes on MR [Baseline and at MR response evaluation up to week 25 of the study]
Changes in diffusion from diffusion-weighted MR
- Patient reported general outcome measures [Baseline and up to 5 years of the study]
Quality of life using EORTC qlq-c30 questionnaire
- Patient reported colo-rectal outcome measures [Baseline and up to 5 years of the study]
Quality of life using EORTC qlq-cr29 questionnaire
- Patient reported bowel-related outcome measures [Baseline and up to 5 years of the study]
Quality of life using low anterior resection syndrome (LARS) score
Eligibility Criteria
Criteria
Inclusion Criteria:
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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.
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ECOG status ≤ 1
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Being willing and able to give full written consent for participation
Exclusion Criteria:
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Previous rectal cancer treatment
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Previous irradiation to the treatment area e.g. prostate cancer
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Hip prosthesis
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Contraindications to MRI
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Pregnancy
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Abnormal DPYD genotype
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Known contraindication to 5-FU, Capecitabine or Oxaliplatin as judged by the investigators
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Haukeland University Hospital | Bergen | Norway | 5021 |
Sponsors and Collaborators
- Haukeland University Hospital
Investigators
- Principal Investigator: Unn Hege Lilleøren, MD, Dept. of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TNT-RECORD