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

Phase 2

Active, not recruiting

• Conditions: Rectal Cancer Stage III
• Interventions: Drug: FOLFOXIRI+Cetuximab regimen

• Registration Number: NCT03391843
• Lead Sponsor: RenJi Hospital

Brief Summary

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

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

Study Timeline

• Study Start: 2017-12-01
• Status Verified: 2018-01
• Study First Submitted: 2018-01-02
• Study First Submitted QC: 2018-01-02
• Last Update Submitted: 2018-01-02
• Study First Posted: 2018-01-05
• Last Update Posted: 2018-01-05
• Primary Completion: 2027-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 100

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
FOLFOXIRI+Cetuximab	FOLFOXIRI+Cetuximab regimen	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.

Primary Outcome Measures

Name	Time	Method
Pelvic complete resection rate	Up to 10 weeks	Pathologic confirmation

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Department of Radiation Oncology,Renji Hospital affiliated to Medical School, Shanghai Jiaotong University; 🇨🇳 Shanghai, S, China