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

Shanghai Jiao Tong University

Status and phase: Active, not recruiting; Phase 2

Conditions: Rectal Cancer Stage III

Treatments: Drug: FOLFOXIRI+Cetuximab regimen

Study type: Interventional

Funder types: Other

Identifiers

NCT03391843

2018CRC R-002

Details and patient eligibility

About

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.

Full description

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

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥ 18 to 75 years at diagnosis
2. Diagnosis of rectal adenocarcinoma
3. ECOG status: 0～1
4. Clinical stage II (T3-4, N0) or stage III (T1-4, N1-2)
5. 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

1. Patient had received pelvic radiotherapy;
2. Patient had received systemic chemotherapy
3. Pregnant and Nursing women
4. Had metastatic disease
5. Uncontrolled co-morbid illnesses or other concurrent disease
6. Patient had second malignant disease within 5 years
7. Patients refused to signed informed consent.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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100 participants in 1 patient group

FOLFOXIRI+Cetuximab

Experimental group

Description:

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.

Treatment:

Drug: FOLFOXIRI+Cetuximab regimen