Consolidation Versus Induction Chemotherapy in Total Neoadjuvant Therapy of Rectal Cancer With High Risk for Recurrence

Study Overview
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Brief Summary
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The purpose of the study is to identify the most promising sequence of modalities in total neoadjuvant treatment of localy advanced rectal cancer with high risk of recurrence

Detailed Description
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International recommendations for the treatment of LARC with a high risk of disease recurrence are inconsistent, regarding TNT. In Germain randomised study more pCR were achieved with consolidation chemotherapy. We will compare our standard approach (induction plus consolidation CT) with consolidation CT.

Official Title
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Induction Versus Consolidation Chemotherapy in Total Neoadjuvant Therapy of Localy Advanced Rectal Cancer With High Risk of Recurrence (ICONA Study)

Conditions
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Locally Advanced Rectal Cancer

Intervention / Treatment
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* Other: consolidation chemotherapy
* Other: induction chemotherapy


Participation Criteria
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Eligibility Criteria
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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 MR imaging: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: consolidation chemotherapy<br>chemoradiation: intensity-modulated irradiation technique with simultaneous integrated boost to the tumor (IMRT-SIB) or with volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (VMAT-SIB) to the total tumor dose of 46.2 Gy in T1-3 tumors and 48.4 Gy in T4 tumors in 22 fractions with concomitant CT with capecitabine (dosage: 825 mg / m2 / 12 h per os continuously from the first to the last day of irradiation). 6 cycles of CAPOX chemotherapy. One cycle of CAPOX CT lasts 3 weeks and consists of capecitabine 1000 mg / m2 / 12h per os for 1-14 days and oxaliplatin 130 mg / m2 intravenously in a two-hour infusion on day 1. | Other: consolidation chemotherapy<br>* 6 cycles CAPOX after chemoradiotherapy<br>|
| Active Comparator: induction chemotherapy<br>4 cycles of induction CAPOX chemotherapy. One cycle of CAPOX CT lasts 3 weeks and consists of capecitabine 1000 mg / m2 / 12h per os for 1-14 days and oxaliplatin 130 mg / m2 intravenously in a two-hour infusion on day 1. Chemoradiation:intensity-modulated irradiation technique with simultaneous integrated boost to the tumor (IMRT-SIB) or with volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (VMAT-SIB) to the total tumor dose of 46.2 Gy in T1-3 tumors and 48.4 Gy in T4 tumors in 22 fractions with concomitant CT with capecitabine (dosage: 825 mg / m2 / 12 h per os continuously from the first to the last day of irradiation). 2 cycles of consolidation CAPOX chemotherapy. | Other: induction chemotherapy<br>* 4 cycles CAPOX before and 2 cycles CAPOX after chemoradiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete remission rate | 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. | 2 weeks after completiton of TNT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | time from randomization to death | after 3 years of follow-up | 
| Survival without recurrence of the disease | time from the end of treatment (in the case of cCR) or from radical surgery to death or recurrence of the disease - whichever comes first. | after 3 years of follow-up | 
| Disease free survival | 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 | after 3 years of follow-up | 
| local control | the time from the end of the treatment (in the case of cCR) or surgery to local recurrence | after 3 years of follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rectal cancer, total neoadjuvant therapy, induction chemotherapy, consolidation chemotherapy