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

Phase 2
Recruiting
Conditions
Locally Advanced Rectal Cancer
Interventions
Combination Product: Chemoradiotherapy
Drug: mFOLFOXIRI
Registration Number
NCT04423965
Lead Sponsor
First Affiliated Hospital of Zhejiang University
Brief Summary

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

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
220
Inclusion Criteria
  1. Aged ≥ 18 to 70 years at diagnosis;
  2. ECOG status 0-2;
  3. Diagnosis of rectal adenocarcinoma(Distal border of the tumor must be located < 12 cm from the anal verge);
  4. MRI examination diagnosed EMVI-positive;
  5. Tumor amenable to curative resection;
  6. 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
  7. Signed informed consent; able to comply with study and/or follow- up procedures
Exclusion Criteria
  1. Hypersensitivity to fluorouracil, oxaliplatin or irinotecan;
  2. Patient had received pelvic radiotherapy;
  3. Patient had received systemic chemotherapy;
  4. History of invasive colon or rectal malignancy, regardless of disease-free interval;
  5. Had metastatic disease;
  6. Patient had second malignant disease within 5 years;
  7. Uncontrolled co-morbid illnesses or other concurrent disease;
  8. Patients refused to signed informed consent.
  9. Pregnant and Nursing women

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Chemoradiotherapy(CRT)ChemoradiotherapyPatients receive standard chemoradiotherapy
mFOLFOXIRImFOLFOXIRIPatients receive 6 cycles of mFOLFOXIRI
Primary Outcome Measures
NameTimeMethod
MFS3 years

metastasis free survival

Secondary Outcome Measures
NameTimeMethod
Tumor downstaging rate2 years

the proportion of tumor downstaging to ypT0-2N0M0

RFS3 years

recurrence-free survival

DFS3 years

disease-free survival

OS5 years

overall survival

pCR2 years

Pathologic complete response rate

Reported Adverse events2 years

The incidence of \>=3 grade adverse events

Trial Locations

Locations (1)

The First Affiliated Hospital, Zhejiang University School of Medicine

🇨🇳

Hangzhou, Zhejiang, China

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