Locally Advanced Rectal Cancer
Conditions
Keywords
Extramural Vascular Invasion, Neoadjuvant, chemotherapy, mFOLFOXIRI
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 mFOLFOXIRI as neoadjuvant chemotherapy alone for EMVI+ LARC.
Detailed description
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.
Interventions
DRUGmFOLFOXIRI
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
Sponsors
First Affiliated Hospital of Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Aged ≥ 18 to 75 years at diagnosis; 2. ECOG status 0 or 1; 3. Signed informed consent; able to comply with study and/or follow- up procedures; 4. Diagnosis of rectal adenocarcinoma; 5. Distal border of the tumor must be located \< 12 cm from the anal verge; 6. MRI examination diagnosed EMVI-positive; 7. Tumor amenable to curative resection; 8. 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. 9. No renal disease that would preclude study treatment or follow-up
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 | Three years | metastasis free survival |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| OS | 5 years | overall survival. |
| Tumor downstaging rate | 2 years | the proportion of tumor downstaging to ypT0-2N0M0 |
| pCR | 2 years | Pathologic complete response rate |
| Reported Adverse events | 2 years | The incidence of \>=3 grade adverse events |
| locoregional recurrence | 3 years | The rate of local recurrence |
| DFS | 3 years | disease-free survival |
| R0 rate | 2 years | R0 resection rate |
Countries
China
Contacts
Primary ContactHua M Hanju, M.D
Backup ContactJiang F Weiqin, M.D
Outcome results
None listed