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

• ClinicalTrials.gov Identifier: NCT03391843
• Recruitment Status: Active, not recruiting
• First Posted: January 5, 2018
• Last Update Posted: January 5, 2018
• Sponsor: RenJi Hospital
• Information provided by (Responsible Party): Yeming, RenJi Hospital

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 (Clinical Trial)
• Estimated 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: December 1, 2017
• Estimated Primary Completion Date: December 31, 2027
• Estimated Study Completion Date: December 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 Name: CPT 11,CAMPTO，Eloxatin，Xelod，Eloxatin,Erbitux

Outcome Measures

Primary Outcome Measures :

1. Pelvic complete resection rate [ Time Frame: Up to 10 weeks ]
   Pathologic confirmation

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

China, S

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

More Information

• Responsible Party: Yeming, Renji Hospital, RenJi Hospital
• ClinicalTrials.gov Identifier: NCT03391843
• Other Study ID Numbers: 2018CRC R-002
• First Posted: January 5, 2018
• Last Update Posted: January 5, 2018
• Last Verified: January 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Yeming, RenJi Hospital:

Local Advanced Rectal Cancer; Neoadjuvant Chemotherapy; FOLFOXIRI; Cetuximab; EGFR wild type

Additional relevant MeSH terms:

Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Cetuximab; Oxaliplatin; Antineoplastic Agents, Immunological; Antineoplastic Agents