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

Phase 3

Recruiting

• Conditions: Rectal Cancer; Neoadjuvant Chemotherapy
• Interventions: Drug: Capox chemotherapy

• Registration Number: NCT04922853
• Lead Sponsor: West China Hospital

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2021-06-04
• Study First Submitted QC: 2021-06-10
• Study First Posted: 2021-06-11
• Study Start: 2021-08-26
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-16
• Last Update Posted: 2022-03-31
• Primary Completion: 2024-12-01
• Study Completion: 2026-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 554

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2 cycles group	Capox chemotherapy	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.
4 cycles group	Capox chemotherapy	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.

Primary Outcome Measures

Name	Time	Method
pathological Tumor Regression Grade evaluation	12 weeks	pTRG

Secondary Outcome Measures

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

Trial Locations

Locations (4)

The Third Affiliated Hospital of Kunming Medical University; 🇨🇳 Kunming, Yunnan, China

Genecast Biotechnology Co., Ltd; 🇨🇳 Wuxi, Jiangsu, China

West China Hospital; 🇨🇳 Chengdu, Sichuan, China

the Third People'S Hospital of Chengdu; 🇨🇳 Chengdu, Sichuan, China