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

Sichuan University

Status and phase: Active, not recruiting; Phase 3

Conditions: Neoadjuvant Chemotherapy; Rectal Cancer

Treatments: Drug: Capox chemotherapy

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04922853

RC-CT-2021

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 554 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age: 18-75 years old; No gender limitation;
2. 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
3. tumor located <=12cm from anal verge by colonoscopy or anal examination
4. no distant metastasis confirmed by CT examination;
5. rectal adenocarcinoma confirmed by pathology,
6. ECOG score: 0-1;
7. Patients with primary rectal cancer who did not receive surgery (except palliative stomy), radiotherapy, systemic chemotherapy or other anti-tumor therapy before enrollment;
8. 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.
9. No history of allergy to platinum drugs when no 5-FU drugs are allergic;
10. 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;
11. Subjects volunteered to participate in this study, signed the informed consent, and showed good compliance and followed up.

Exclusion criteria

1. patients suspect to Lynch syndrome;
2. Patients showed distant metastasis during treatment;
3. Previously or coexisting malignancies (including concurrent colon cancer), except for cured basal cell carcinoma of the skin and carcinoma in situ of the cervix;
4. pregnant or breastfeeding women;
5. Patients with severe cardiovascular diseases and diabetes that is not easily controlled;
6. People with mental disorders;
7. Severe infection;
8. sever renal disfunction;
9. History of gastrointestinal fistula, perforation, bleeding, or severe ulcer;
10. Allergic to 5-FU or platinum;
11. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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554 participants in 2 patient groups

2 cycles group

Experimental group

Description:

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.

Treatment:

Drug: Capox chemotherapy

4 cycles group

Other group

Description:

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.

Treatment:

Drug: Capox chemotherapy