Neoadjuvant mFOLFOXIRI Chemotherapy Alone for Extramural Vascular Invasion Positive Locally Advanced Rectal Cancer

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 mFOLFOXIRI as neoadjuvant chemotherapy alone for EMVI+ LARC.

Detailed Description
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It is an investigator-initiated, single institution, prospective, single-arm clinical study to evaluate the efficacy and safety of FOLFOXIRI as neoadjuvant chemotherapy alone for EMVI+ LARC.Patients of LARC with EMVI+ evaluated by pelvic magnetic resonance imaging (MRI) were enrolled in this trial. All EMVI+ LARC will receive the study regimen every 2 weeks for 6 cycles. MRI will be performed after 3 cycles of chemotherapy to assess clinical response.MRI was performed to assess clinical response after chemotherapy. 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).If the tumor response is good enough(partial response or complete response), the patient will receive another 3 cycles of FOLFOXIRI 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. All patients will receive 6 cycles of mFOLFOX6 or 4 cycles XELOX as adjuvant chemotherapy after TME.

Official Title
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Neoadjuvant mFOLFOXIRI Chemotherapy Alone for Extramural Vascular Invasion(EMVI) Positive Rectal Cancer: A Phase II, Single-arm, Prospective Clinical Study

Conditions
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Locally Advanced Rectal Cancer

Intervention / Treatment
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* Drug: mFOLFOXIRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 18 to 75 years at diagnosis; ECOG status 0 or 1; Signed informed consent; able to comply with study and/or follow- up procedures; 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 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: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mFOLFOXIRI<br>patients received FOLFOXIRI alone for 6 cycles before surgery. | Drug: mFOLFOXIRI<br>* irinotecan* 135 mg/m² + oxaliplatin 68 mg/m² + leucovorin 400 mg/m² + 5-FU 2400 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle<br>* Other names: Irinotecan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MFS | metastasis free survival | Three 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 | 
| R0 rate | R0 resection rate | 2 years | 
| locoregional recurrence | The rate of local recurrence | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Extramural Vascular Invasion, Neoadjuvant, chemotherapy, mFOLFOXIRI