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

Sponsor

RenJi Hospital (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03391843

Collaborator

(none)

100

Enrollment

Location

Arm

121

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Rectal Cancer Stage III	Drug: FOLFOXIRI+Cetuximab regimen	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 1, 2017

Anticipated Primary Completion Date :

Dec 31, 2027

Anticipated Study Completion Date :

Dec 31, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FOLFOXIRI+Cetuximab 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 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 Other Names: CPT 11,CAMPTO，Eloxatin，Xelod，Eloxatin,Erbitux

Arm

Intervention/Treatment

Experimental: FOLFOXIRI+Cetuximab

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

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

Other Names:

CPT 11,CAMPTO，Eloxatin，Xelod，Eloxatin,Erbitux

Outcome Measures

Primary Outcome Measures

Pelvic complete resection rate [Up to 10 weeks]
Pathologic confirmation

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Radiation Oncology,Renji Hospital affiliated to Medical School, Shanghai Jiaotong University	Shanghai	S	China	2

Sponsors and Collaborators

RenJi Hospital

Investigators

Principal Investigator: Ming Ye, Master, Department of Radiation Oncology,Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine