Neoadjuvant Chemotherapy Combined With Cetuximab for EGFR Wild Type Locally Advanced Rectal Cancer

Study Overview
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Brief Summary
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A number of pilot studies had shown high rate of complete resection after neoadjuvant chemotherapy alone for local advanced rectal cancer(LARC), but they did not increase the ratio of pathological complete response (pCR) which was associated with improvement of overall survival (OS). On the other hand,some clinical trials show that triple active cytotoxic agents (Fluorouracil, Oxaliplatin, Irinotecan, FOLFOXIRI) combined with cetuximab for EGFR wild type metastatic colorectal cancer had more effective than double agents.Therefore,a hypothesis is the FOLFOXIRI+Cetuximab as the neoadjuvant chemotherapy regimen might improve the patient's ratio of pCR.

Detailed Description
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This is a multicenter, phase II trial to assess the efficacy and safety of triplet regimen (FOLFOXIRI) combined with cetuximab for patients with EGFR wild type LARC. After 4 cycles of FOLFOXIRI+cetuximab 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 the multidisciplinary team (MDT),otherwise, the patients will receive pelvic radiotherapy(45Grey/25Fraction and 5.4Grey/3Fraction boost to the tumor bed) combined with capecitabine(625 mg/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. FOLFOXIRI+Cetuximab Irinotecan 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h + Cetuximab 500 mg/m²,all on day 1 of each 2 weeks cycle for 4-6 cycles, Other Names: CPT11，CAMPTO Eloxatin Xelod Erbitux

Official Title
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FOLFOXIRI Combined With Cetuximab as a Neoadjuvant Chemotherapy for EGFR Wild Type Locally Advanced Rectal Cancer:A Phase II Study

Conditions
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Rectal Cancer Stage III

Intervention / Treatment
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* Drug: FOLFOXIRI+Cetuximab regimen


Participation Criteria
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Eligibility Criteria
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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: 1),Leukocytes ≥ 3.0 x109/ L, 2),Absolute neutrophil count (ANC) ≥ 1.5 x109/ L 3),Platelet count ≥ 100 x109/ L, 4),Hemoglobin (Hb) ≥ 9g/ dL. 5),Total bilirubin ≤1.5 x the upper limit of normal (ULN). 6),Alanine aminotransferase (ALT)/Aspartate aminotransferase (AST) ≤ 3 x ULN. 7),Serum creatinine ≤ 1.5 x the ULN. 8),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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FOLFOXIRI+Cetuximab<br>FOLFOXIRI+Cetuximab regimen:Irinotecan 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h and cetuximab 500mg/m²,all on day 1 of each 2 weeks cycle for 4-6 cycles. | Drug: FOLFOXIRI+Cetuximab regimen<br>* FOLFOXIRI+Cetuximab Irinotecan 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h +Cetuximab 500mg/m²,all on day 1 of each 2 weeks cycle<br>* Other names: CPT 11,CAMPTO，Eloxatin，Xelod，Eloxatin,Erbitux;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pelvic complete resection rate | Pathologic confirmation | Up to 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of local control | Imaging diagnosis | 3 years | 
| Disease free survival (DFS) | Imaging diagnosis | Three years | 
| Overall survival | Record document | Three years | 
| The rate of receive chemoradiation | Record document | Up to 10 weeks | 
| The rate of clinical complete response after 4 cycles of FOLFOXIRI | Pathologic confirmation | Up to 10 weeks | 
| The incidence of >=3 grade adverse events | Common Terminology Criteria for Adverse Events v3.0 (CTCAE) | Two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Local Advanced Rectal Cancer, Neoadjuvant Chemotherapy, FOLFOXIRI, Cetuximab, EGFR wild type