Locally Advanced Rectal Cancer
Conditions
Keywords
rectal cancer, total neoadjuvant therapy, induction chemotherapy, consolidation chemotherapy
Brief summary
The purpose of this study is to identify the most promising treatment sequence in total neoadjuvant therapy for locally advanced rectal cancer with a high risk of recurrence.
Detailed description
International recommendations for the treatment of locally advanced rectal cancer with a high risk of disease recurrence are inconsistent regarding the optimal sequence of total neoadjuvant therapy. In a German randomized study, a higher rate of pathological complete response was observed with consolidation chemotherapy. This study compares induction chemotherapy followed by chemoradiotherapy and consolidation chemotherapy with chemoradiotherapy followed by consolidation chemotherapy in patients with locally advanced rectal cancer and high-risk features for recurrence.
Interventions
DRUGConsolidation CAPOX Chemotherapy
Six cycles of CAPOX chemotherapy are administered after chemoradiotherapy. CAPOX consists of capecitabine and oxaliplatin according to the study protocol.
DRUGInduction CAPOX Chemotherapy
Four cycles of CAPOX chemotherapy are administered before chemoradiotherapy, followed by two cycles of CAPOX chemotherapy after chemoradiotherapy. CAPOX consists of capecitabine and oxaliplatin according to the study protocol.
Sponsors
Institute of Oncology Ljubljana
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants are randomized to one of two treatment sequences of total neoadjuvant therapy: induction chemotherapy followed by chemoradiotherapy and consolidation chemotherapy, or chemoradiotherapy followed by consolidation chemotherapy.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
- histologically proven rectal adenocarcinoma * no distant metastases on CT scan (M0 disease) * at least one high risk factor for disease recurrence identified on magnetic resonance imaging (MRI): * T4 tumor (cT4) * N2 disease (cN2) * extramural venous invasion (cEMVI+) * positive lateral lymph nodes * distance of tumor to mesorectal fascia or positive lymph nodes is 1 mm or less (cMRF+) * capacity for informed consent * willingness to attend regular check-ups during and after treatment
Exclusion criteria
history of previous irradiation in the pelvic area * absolute contraindications for MR imaging * distant metastases cannot be reliably excluded * synchronous cancer * chronic inflammatory bowel disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| complete remission rate | 2 weeks after completion of TNT | The proportion of complete responses will be defined as the sum of the proportions of pCR in operated patients and cCR in non-operated patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | after 3 years of follow-up | time from randomization to death |
| Survival without recurrence of the disease | after 3 years of follow-up | time from the end of treatment (in case of cCR) or from radical surgery to death or recurrence of the disease - whichever comes first. |
| Disease free survival | after 3 years of follow-up | the time from the end of treatment (in the case of cCR) or surgery to the recurrence of disease, the onset of new cancer, death from cancer or other causes |
| local control | after 3 years of follow-up | the time from the end of the treatment (in the case of cCR) or surgery to local recurrence |
Countries
Slovenia
Contacts
PRINCIPAL_INVESTIGATORVaneja Velenik, PD
Institute of Oncology Ljubljana
Outcome results
None listed