Neoadjuvant FOLFOXIRI Versus CapeOX Chemotherapy for Local Advanced Rectal Cancer

Study Overview
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Brief Summary
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This is a phase III randomized controlled trial comparing the efficacy and safety of FOLFOXIRI versus CapeOX as neoadjuvant regimen in treating patients with middle and upper locally advanced (MRI T3-4 or N+) rectal cancer. This study aims to optimize the neoadjuvant therapy for patients with anus-preserving resectable locally advanced rectal cancer, so as to improve the prognosis of them. It remains unclear about whether FOLFOXIRI or CapeOX neoadjuvant chemotherapy is more effective for locally advanced rectal cancer.

Official Title
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Neoadjuvant FOLFOXIRI Chemotherapy Versus CapeOX Chemotherapy for Local Advanced Rectal Cancer: An Open Label Randomized Controlled Phase III Trial

Conditions
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Rectal Cancer

Intervention / Treatment
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* Drug: FOLFOXIRI
* Drug: CapeOX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: MRI evaluated of T3-4 or N+ rectal cancer; Pathologically diagnosed of rectal adenocarcinoma; 18 to 75 years old; Distance from lower margin of tumor to anus <15 cm and suitable for anus-preserving resection; Tumor amenable to radical resection; Treatment-na?ve patients with no previous systemic chemotherapy, radiotherapy or local excision for treating rectal cancer; Laboratory requirements conducted within 7 days of starting study treatment: Neutrophil count ≥ 1.5×10^9/L, Platelet count ≥ 100×10^9 /L, Hemoglobin ≥ 80 g/L, Serum bilirubin ≤ 24umol/L, Alanine aminotransferase and aspartate aminotransferase ≤ 60 U/L, Serum creatinine ≤ 110 umol/L; Be capable to receive a surgery; No second tumor at present or in the past 5 years, except skin basal cell carcinoma, skin squamous cell carcinoma, or any in situ cancer; No previous systemic chemotherapy for treating colorectal cancer; Life expectancy of more than 3 months; No current pregnancy or breast-feeding, and subjects at childbearing age shall take method of contraception; Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1; Be willing and able to understand the study and to provide written informed consent. Exclusion Criteria: End-stage cachexia patients; Cardiopulmonary dysfunction or liver and kidney dysfunction, and unable to tolerate chemotherapy or surgery; Metastatic carcinoma; Incomplete or complete intestinal obstruction; Known to be allergic to capecitabine, 5-Fu, oxaliplatin or irinotecan; Pregnant or lactating women; or women who have fertility but have not taken at taken adequate contraceptive measures; Have vital organ failure or other severe diseases, including but not limited to coronary heart disease, cardiovascular diseases, or myocardial infarction within 12 months before being included; severe neurological or psychiatric historysevere infection; active disseminated intravascular coagulation; active hepatitis, severe coagulation disorder patients; History of other malignancy within the past 5 years except effectively treated skin basal cell carcinoma, skin squamous cell carcinoma, or any in situ cancer; Serious organic disease including but not limited to heart, kidney, brain, and lung.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A: FOLFOXIRI<br>Neoadjuvant chemotherapy with 3-4 cycles of FOLFOXIRI regimen, followed by surgery | Drug: FOLFOXIRI<br>* irinotecan* 165 mg/m² iv continue for 1.5 hours, D1 oxaliplatin 85 mg/m² iv continue for 2 hours, D1 leucovorin 400 mg/m² iv continue for 2 hours, D1 5-FU 2400 3200 mg/m² cont. inf. 48h, D1 repeat every 2 weeks (Q2W)<br>* Other names: Surgery;|
| Experimental: B: CapeOX<br>Neoadjuvant chemotherapy with 2-3 cycles of CapeOX regimen, followed by surgery | Drug: CapeOX<br>* oxaliplatin 130 mg/m2 iv continue for 2 hours, D1 capecitabine 1000mg/m2/d PO Bid, once every morning and evening D1-14 repeat every 3 weeks (Q3W)<br>* Other names: Surgery;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year disease free survival | Defined as the length of time from the date of randomization until the first documented date of progression or death from any cause, whichever comes first. Compare 3-year disease free survival in patients with locally advanced rectal cancer treated with either FOLFOXIRI or CapeOX neoadjuvant chemotherapy. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pathologic complete response rate | Defined as the ratio of patients with pathologic TRG 0 | 1 year | 
| major pathologic response rate | Defined as the ratio of patients with pathologic TRG 0 or 1 | 1 year | 
| objective response rate | Defined as the ratio of patients with MRI-TRG 1, 2 or 3 | 1 year | 
| local recurrence rate | Defined as the ratio of patients with local recurrence within 3 years. | 3 years | 
| overall survival | Defined as the length of time from randomization date until the date of death from any cause. | 5 years | 
| quality of life as assessed by EORTC QOL-C30 | Quality of life after neoadjuvant chemotherapy is assessed by questionaires EORTC QOL-C30 version 3 | 3 years | 
| quality of life as assessed by EORTC QOL-CR29 | Quality of life after neoadjuvant chemotherapy is assessed by questionaires EORTC QOL-CR29. | 3 years | 
| adverse event | Number of patients with adverse events and severity according to NCI CTC 5.0 after neoadjuvant chemotherapy. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoadjuvant chemotherapy, Locally advanced rectal cancer, FOLFOXIRI, CapeOX