A Trial of Neoadjuvant mFOLFOXIRI Versus CRT in the EMVI Positive LARC

Study Overview
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Brief Summary
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Extramural Vascular Invasion Positive(EMVI+) is a high risk of distant metastasis for locally advanced rectal cancer(LARC) after resection. The study is to evaluate the efficacy and safety of FOLFOXIRI as neoadjuvant chemotherapy alone for EMVI+ LARC in contrast to the efficacy of standard Chemoradiotherapy (CRT).

Detailed Description
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It is an investigator-initiated, multicentered, randomized controlled clinical study to evaluate the efficacy and safety of mFOLFOXIRI as neoadjuvant chemotherapy alone for EMVI+ LARC in contrast to standard chemoradiotherapy. Patients of LARC with EMVI+ evaluated by pelvic magnetic resonance imaging (MRI) are enrolled in this trial. All patients will be randomized divided into two groups. Experimental group will receive 3 cycles of mFOLFOXIRI, followed to be performed MRI to assess clinical response. If the tumor response is good enough (partial response or complete response), the patient will receive another 3 cycles of mFOLFOXIRI then surgery. On the contrary, if the tumor shows poor response (stable disease or progressive disease) or with mesorectal fascia-positive or ycT4a/b after re-evaluation, radiotherapy will be performed combined with capecitabine before operation. Control group will receive standard capecitabine based chemoradiotherapy. Patients with mesorectal fascia-positive or ycT4a/b after re-evaluation would receive radiation before surgery, whereas responders would have immediate total mesorectal excision (TME). All patients will receive 4 cycles of XELOX as adjuvant chemotherapy after TME.

Official Title
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A Multicenter Randomized Controlled Phase II Trial of Neoadjuvant mFOLFOXIRI Versus Routine Chemoradiotherapy in the EMVI Positive Locally Advanced Rectal Cancer (TRICHEMO)

Conditions
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Locally Advanced Rectal Cancer

Intervention / Treatment
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* Drug: mFOLFOXIRI
* Combination Product: Chemoradiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 18 to 70 years at diagnosis; ECOG status 0-2; Diagnosis of rectal adenocarcinoma(Distal border of the tumor must be located < 12 cm from the anal verge); MRI examination diagnosed EMVI-positive; Tumor amenable to curative resection; Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment: (1) Neutrophilic granulocytes ≥ 3.0 x10^9/L, Platelet count ≥ 75 x 10^9/L, Hemoglobin (Hb) ≥ 90g/L; (2) bilirubin ≤1.5 x the upper limit of normal (ULN),Alanine aminotransferase (ALT)/Aspartate aminotransferase (AST) ≤ 2.5 x ULN; (3) Serum creatinine ≤ 1.5 x ULN.No renal disease that would preclude study treatment or follow-up Signed informed consent; able to comply with study and/or follow- up procedures Exclusion Criteria: Hypersensitivity to fluorouracil, oxaliplatin or irinotecan; Patient had received pelvic radiotherapy; Patient had received systemic chemotherapy; History of invasive colon or rectal malignancy, regardless of disease-free interval; Had metastatic disease; Patient had second malignant disease within 5 years; Uncontrolled co-morbid illnesses or other concurrent disease; Patients refused to signed informed consent. Pregnant and Nursing women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mFOLFOXIRI<br>Patients receive 6 cycles of mFOLFOXIRI | Drug: mFOLFOXIRI<br>* irinotecan 165 mg/m² IV day 1+ oxaliplatin 85 mg/m² IV day 1 + leucovorin 400 mg/m² day 1, fluorouracil 1200mg/m²/day *2 days (total 2400 mg/m² over 48 hours) continuous infusion starting on day 1 of each 2 weeks cycle<br>|
| Experimental: Chemoradiotherapy(CRT)<br>Patients receive standard chemoradiotherapy | Combination Product: Chemoradiotherapy<br>* Capecitabine based chemoradiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MFS | metastasis free survival | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor downstaging rate | the proportion of tumor downstaging to ypT0-2N0M0 | 2 years | 
| pCR | Pathologic complete response rate | 2 years | 
| RFS | recurrence-free survival | 3 years | 
| DFS | disease-free survival | 3 years | 
| OS | overall survival | 5 years | 
| Reported Adverse events | The incidence of >=3 grade adverse events | 2 years |