Clinical trial NCT03391843: Neoadjuvant Chemotherapy Combined With Cetuximab for EGFR Wild Type Locally Advanced Rectal Cancer
Official title: FOLFOXIRI Combined With Cetuximab as a Neoadjuvant Chemotherapy for EGFR Wild Type Locally Advanced Rectal Cancer:A Phase II Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Rectal Cancer Stage III
Keywords: Local Advanced Rectal Cancer
Neoadjuvant Chemotherapy
FOLFOXIRI
Cetuximab
EGFR wild type
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
First posted: 2018-01-05
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Pelvic complete resection rate
timeFrame: Up to 10 weeks
Secondary outcomes:
measure: The rate of local control
timeFrame: 3 years
measure: Disease free survival (DFS)
timeFrame: Three years
measure: Overall survival
timeFrame: Three years
measure: The rate of receive chemoradiation
timeFrame: Up to 10 weeks
measure: The rate of clinical complete response after 4 cycles of FOLFOXIRI
timeFrame: Up to 10 weeks
measure: The incidence of >=3 grade adverse events
timeFrame: Two years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Department of Radiation Oncology,Renji Hospital affiliated to Medical School, Shanghai Jiaotong University
state: S
Study officials:
affiliation: Department of Radiation Oncology,Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine
name: Ming Ye, Master
role: PRINCIPAL_INVESTIGATOR
References: