Total Neoadjuvant Therapy in Rectal Cancer Treatment

Study Overview
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Brief Summary
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This is a randomized, controlled, parallel study to determine the efficiency and safety of total neoadjuvant therapy in rectal cancer treatment.

Detailed Description
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In this randomized, controlled, parallel study we will comparison total neoadjuvant therapy with standard neoadjuvant therapy in rectal cancer treatment. Complete pathological response rate will be the primary endpoint in patients, who will undergoing surgery. In cases of complete clinical response we will provide watch and wait approach. Compliance of treatment and oncologic results will be the second endpoint.

Official Title
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Total Neoadjuvant Therapy in Rectal Cancer Treatment

Conditions
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Rectal Cancer

Intervention / Treatment
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* Combination Product: Concurrent Chemoradiotherapy
* Procedure: TME
* Drug: consolidation chemotherapy
* Drug: adjuvant chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have signed an approved informed consent form for the stud; Histologically confirmed rectal adenocarcinoma low (cT2-4N0-2M0) or mid rectum (сТ2-T4N1-2M0); Exclusion Criteria: rectal cancer recurrence; Primary-multiple tumours of other localizations; pelvis radiotherapy in anamnesis; pregnancy, breastfeeding; distant metastasis; ECOG score 3-4

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: Parallel Assignment
Interventional Model Description: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: total neoadjuvant therapy<br>Total neoadjuvant therapy consisted chemoradiotherapy with capecitabine and nine weeks of consolidation chemotherapy with XELOX prior to surgery and adjuvant therapy if necessary. | Combination Product: Concurrent Chemoradiotherapy<br>* 50Gy in 25 fractions to the primary tumor and to mesorectal, presacral,and internal iliac lymph nodes. Concurrent chemotherapy: Capecitabine 1650 mg/m2/d<br>* Other names: Radiotherapy;Procedure: TME<br>* Total mesorectal excision<br>Drug: consolidation chemotherapy<br>* Intravenous infusion of oxaliplatin (130 mg/m2 over 2 h) on day 1 and oral administration of capecitabine (1000 mg/m2 twice daily) from day 1 to day 14, is repeated every 3 weeks for 3 courses, 3 weeks per course<br>* Other names: CAPOX;Drug: adjuvant chemotherapy<br>* Administration of l-LV (400 mg/m2) and oxaliplatin (85 mg/ m2) by intravenous infusion over 2 h, followed by rapid intravenous infusion (iv) of 5-FU (400 mg/m2) and then slow infusion (civ) of 5-FU (2400 mg/m2 over 46 h), is repeated every 2 weeks for 6-12 cycles<br>* Other names: mFOLFOX;|
| Active Comparator: standard therapy<br>Standard therapy (neoadjuvant chemoradiotherapy, surgery, adjuvant chemotherapy) | Combination Product: Concurrent Chemoradiotherapy<br>* 50Gy in 25 fractions to the primary tumor and to mesorectal, presacral,and internal iliac lymph nodes. Concurrent chemotherapy: Capecitabine 1650 mg/m2/d<br>* Other names: Radiotherapy;Procedure: TME<br>* Total mesorectal excision<br>Drug: adjuvant chemotherapy<br>* Administration of l-LV (400 mg/m2) and oxaliplatin (85 mg/ m2) by intravenous infusion over 2 h, followed by rapid intravenous infusion (iv) of 5-FU (400 mg/m2) and then slow infusion (civ) of 5-FU (2400 mg/m2 over 46 h), is repeated every 2 weeks for 6-12 cycles<br>* Other names: mFOLFOX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of complete responses | The rate of pathological or clinical complete responses | 3-6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of R0-resections | Rate of R0-resections | immediately after surgery | 
| Rate of compliance with radiotherapy and chemotherapy | Rate of complications III-VI grade of radiotherapy (RTOG) and chemotherapy (NCI-CTC) | 6-8 months | 
| rate of intraoperative and postoperative complications | Frequency and structure of intraoperative and postoperative complications according to the Clavien-Dindo classification | 0-30 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rectal cancer, total neoadjuvant therapy, colorectal disease