Rectal Cancer
Conditions
Keywords
Local Advanced Rectal Cancer, Total Neoadjuvant Therapy, FOLFOXIRI
Brief summary
The concurrent neoadjuvant chemoradiation therapy is standard care for local advanced rectal cancer (LARC), however, this regimen may induce sorts of adverse events, and part of them even more severer. A number of pilot studies had shown high rate of complete resection after neoadjuvant chemotherapy alone, but the results did not increase the ratio of pathological complete response (pCR), which was associated with overall survival (OS). Here, the investigators adopt the three active cytotoxic agents (Fluorouracil, Oxaliplatin, Irinotecan, FOLFOXIRI) as the neoadjuvant chemotherapy regimen to replace the concurrent chemoradiation and to improve the ratio of pCR further.
Detailed description
This is a multicenter, phase II trial to assess the efficacy/safety of triplet regimen (FOLFOXIRI) for patients with LARC. After 4 cycles of FOLFOXIRI and 2 weeks later, the patients will be evaluated by senior radiologist, oncologist and surgeon through pelvic MRI, CT and Positron Emission Computed Tomography (PET-CT). The patients will go to surgery (TME) if the tumor response is good enough to have complete resection under the decision of MDT,otherwise, the patients will receive pelvic radiotherapy(45Grey/25Fraction and 5.4Grey/3Fraction boost to the tumor bed) combined with capecitabine(625mg/M\^2, bid po, d1-5, qw), and additional four cycles of modified FOLFOX6 (mFOLFOX6) or Oxaliplatin 135mg/m²plus Capecitabine 1.0/m² bid po(XELOX) of each 3 weeks cycle for 2 cycles chemotherapy before TME. All patients will receive 6-8 cycles of mFOLFOX6 or 4-5 cycles XELOX as adjuvant chemotherapy after TME.
Interventions
DRUGFOLFOXIRI
Irinotecan\* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle for 4-6 cycles, Chemoradiation for patients who are not suitable to surgery: Pelvic radiotherapy(45Grey/25Fraction and 5.4Grey/3Fraction boost to the tumor bed) combined with capecitabine(625mg/m², bid po, d1-5, qw), and additional four cycles of modified FOLFOX6 (mFOLFOX6) or Oxaliplatin 135mg/m²plus Capecitabine 1.0/m² bid po(XELOX) of each 3 weeks cycle for 2 cycles chemotherapy before TME. All patients will receive 6-8 cycles of mFOLFOX6 or 4-5 cycles XELOX as adjuvant chemotherapy after TME.
Sponsors
RenJi Hospital
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
* Age ≥ 18 to 75 years at diagnosis * Diagnosis of rectal adenocarcinoma * ECOG status: 0～1 * Clinical stage II (T3-4, N0) or stage III (T1-4, N1-2) * Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment: * Leukocytes ≥ 4.0 x109/ L, * Absolute neutrophil count (ANC) ≥ 2.0 x109/ L * Platelet count ≥ 100 x109/ L, * Hemoglobin (Hb) ≥ 9g/ dL. * Total bilirubin ≤1.5 x the upper limit of normal (ULN). * Alanine aminotransferase (ALT) ≤ 3 x ULN * Aspartate aminotransferase (AST) ≤ 3 x ULN. * Serum creatinine ≤ 1.5 x the ULN. * Signed informed consent;
Exclusion criteria
* Patient had received pelvic radiotherapy * Patient had received systemic chemotherapy * Pregnant and Nursing women * Had metastatic disease * Uncontrolled co-morbid illnesses or other concurrent disease * Patient had second malignant disease within 5 years * Patients refused to signed informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pelvic complete resection rate | Up to 10 weeks | Pathologic confirmation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease free survival (DFS) | 3 years | Imaging diagnosis |
| Overall survival | 3 years | Record document |
| The rate of receive chemoradiation | Up to 10 weeks | Record document |
| The rate of local control | 3 years | Imaging diagnosis |
| The rate of pathological complete response after 4 cycles of FOLFOXIRI | Up to 10 weeks | Pathologic confirmation |
| The incidence of >=3 grade adverse events | 2 years | Common Terminology Criteria for Adverse Events v3.0 (CTCAE) |
| The rate of clinical complete response after 4 cycles of FOLFOXIRI | Up to 10 weeks | Imaging diagnosis |
Countries
China
Contacts
Primary ContactMing Ye, Master
Backup ContactQi Lu, Master
Outcome results
None listed