A Phase II Study of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer
Overview
- Phase
- Phase 2
- Intervention
- FOLFOXIRI
- Conditions
- Rectal Cancer
- Sponsor
- RenJi Hospital
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- Pelvic complete resection rate
- Last Updated
- 8 years ago
Overview
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.
Investigators
Eligibility Criteria
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).
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.
Arms & Interventions
FOLFOXIRI
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
Intervention: FOLFOXIRI
Outcomes
Primary Outcomes
Pelvic complete resection rate
Time Frame: Up to 10 weeks
Pathologic confirmation
Secondary Outcomes
- The rate of clinical complete response after 4 cycles of FOLFOXIRI(Up to 10 weeks)
- The rate of pathological complete response after 4 cycles of FOLFOXIRI(Up to 10 weeks)
- The incidence of >=3 grade adverse events(2 years)
- The rate of local control(3 years)
- Disease free survival (DFS)(3 years)
- Overall survival(3 years)
- The rate of receive chemoradiation(Up to 10 weeks)