Comparison of the Pathological Effect Between 2 and 4 Cycles Neoadjuvant CAPOX for Low/Intermediate Risk II/III Rectal Cancer

Study Overview
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Brief Summary
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To compare the pathological effect between 2 cycles and 4 cycles of Capox regimen as neoadjuvant chemotherapy for low/ intermediate risk stage II/III rectal cancer.

Detailed Description
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Neoadjuvant Chemotherapy alone has showed much benefit for low/ intermediate risk stage II/III rectal cancer which would be verified by the PROSPECT trial. However, the effect of the Neoadjuvant chemotherapy was heterogeneous in different patients. It's important to verify those chemo-resistant cases as early as possible. So that, this trial will compare the pathological effect between 2 cycles and 4 cycles of Capox regimen as neoadjuvant chemotherapy for low/ intermediate risk stage II/III rectal cancer to explore whether those chemotherapeutic non-responders after 2 cycles Capox was non-inferior to those after 4 cycles chemotherapy.

Official Title
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Comparison of the Pathological Effect Between 2 and 4 Cycles Neoadjuvant CAPOX for Low/Intermediate Risk II/III Rectal Cancer：a Prospective, Non-inferior, Randomized, Controlled Trial

Conditions
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Rectal Cancer, Neoadjuvant Chemotherapy

Intervention / Treatment
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* Drug: Capox chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-75 years old; No gender limitation; Patients diagnosed with low/intermediate risk stage II/III rectal cancer under MRI and transanal ultrasound,defined as: low:T3a-bN0-1M0, EMVI (±), MRF (-) (≥2mm); Middle-high rectal cancer: T3a-cN0-1M0, EMVI (±), MRF (-) (≥2mm); No more than 3 lymph nodes with short diameter over 8mm or highly suspected metastases; Patients with very low rectal cancer who met the above criteria and could achieve negative circumferential resection margin under ELAPE surgery could be included in the group tumor located <=12cm from anal verge by colonoscopy or anal examination no distant metastasis confirmed by CT examination; rectal adenocarcinoma confirmed by pathology, ECOG score: 0-1; Patients with primary rectal cancer who did not receive surgery (except palliative stomy), radiotherapy, systemic chemotherapy or other anti-tumor therapy before enrollment; Main organs function normally, that is, meet the following characteristics: ① Blood routine examination criteria should meet: Hb ≥9g/dL, WBC ≥ 3.5/4.0×109/L, neutrophils ≥ 1.5×109/L, PLT≥ 100×109/L. ② Biochemical tests should meet the following criteria: CREA and BIL ≤ 1.0 times upper limit of normal (ULN), ALT and AST≤ 2.5 times upper limit of normal (ULN), alkaline phosphatase (ALP) ≤2.5×UNL, total bilirubin (TBIL) ≤1.5×UNL. No history of allergy to platinum drugs when no 5-FU drugs are allergic; Women of childbearing age must have had a pregnancy test (serum or urine) 7 days prior to enrolment, be negative, and be willing to use an appropriate method of contraception during the trial and 8 weeks after the last dosing. For men, surgical sterilization or consent to use an appropriate method of contraception during the trial or for 8 weeks after the last dosing; Subjects volunteered to participate in this study, signed the informed consent, and showed good compliance and followed up. Exclusion Criteria: patients suspect to Lynch syndrome; Patients showed distant metastasis during treatment; Previously or coexisting malignancies (including concurrent colon cancer), except for cured basal cell carcinoma of the skin and carcinoma in situ of the cervix; pregnant or breastfeeding women; Patients with severe cardiovascular diseases and diabetes that is not easily controlled; People with mental disorders; Severe infection; sever renal disfunction; History of gastrointestinal fistula, perforation, bleeding, or severe ulcer; Allergic to 5-FU or platinum; The presence of serious gastrointestinal diseases that affect the absorption of oral chemotherapeutic drugs; (12) Participants in additional clinical trials within 4 weeks prior to the start of treatment.

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: 2 cycles group<br>patients which recruited have 2 cycles Capox regimen (oxaliplatin: 130 mg/m2 iv d 1, capecitabine: 1000 mg/m2 bid d 1-14, repeated at 3 week intervals), then those patients with no sever chemotheraputic AE, have TME operation after reevaluation and randomization. | Drug: Capox chemotherapy<br>* oxaliplatin: 130 mg/m2 iv d 1, capecitabine: 1000 mg/m2 bid d 1-14, repeated at 3 week intervals<br>|
| Other: 4 cycles group<br>patients which recruited have 2 cycles Capox regimen (oxaliplatin: 130 mg/m2 iv d 1, capecitabine: 1000 mg/m2 bid d 1-14, repeated at 3 week intervals), then those patients with no sever chemotheraputic AE, have two more cycles chemotherapy and TME operation after reevaluation and randomization. | Drug: Capox chemotherapy<br>* oxaliplatin: 130 mg/m2 iv d 1, capecitabine: 1000 mg/m2 bid d 1-14, repeated at 3 week intervals<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pathological Tumor Regression Grade evaluation | pTRG | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of chemotherapeutic complication |  | 12 weeks | 
| 3-year overall survival | the cumulative overall survival rate of the patients(events defined as all caused death) | 3 year after recruiting | 
| disease free survival | the cumulative disease free survival rate of the patients(events defined as tumor recurrence at any sites) | 3 year after recruiting | 
| cumulative distant recurrence rate | cumulative recurrence rate of Rectal cancer after the radical surgery outside the pelvic cavity | 3 year after recruiting | 
| cumulative local recurrence rate | cumulative recurrence rate of Rectal cancer after the radical surgery within the pelvic cavity or in the wounds | 3 year after recruiting |