Locally Advanced Rectal Cancer
Conditions
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.
Interventions
DRUGmFOLFOXIRI
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
COMBINATION_PRODUCTChemoradiotherapy
Capecitabine based chemoradiotherapy
Sponsors
First Affiliated Hospital of Wenzhou Medical University
Zhejiang Cancer Hospital
First Affiliated Hospital of Zhejiang University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MFS | 3 years | metastasis free survival |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| pCR | 2 years | Pathologic complete response rate |
| RFS | 3 years | recurrence-free survival |
| Tumor downstaging rate | 2 years | the proportion of tumor downstaging to ypT0-2N0M0 |
| OS | 5 years | overall survival |
| Reported Adverse events | 2 years | The incidence of \>=3 grade adverse events |
| DFS | 3 years | disease-free survival |
Countries
China
Contacts
Primary ContactGuosheng Wu, MD
Backup ContactWeiqin Jiang, MD
Outcome results
None listed