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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer; Neoadjuvant Chemotherapy
• Intervention / Treatment: Drug: Capox chemotherapy

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 Type: Interventional
• Enrollment (Anticipated): 554
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ziqiang Wang, MD; Phone Number: 18980602028; Email: wangziqiang@scu.edu.cn
• Study Contact Backup: Name: Xiangbing Deng, MD; Phone Number: 13730677124; Email: 247940362@qq.com

Study Locations

• China
  • Jiangsu
    • Wuxi, Jiangsu, China, 214104
      • Not yet recruiting
      • Genecast Biotechnology Co., Ltd
      • Contact: Biao Mu, PhD; Phone Number: 180908466070
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Recruiting
      • West China Hospital
      • Contact: Ziqiang Wang, MD; Phone Number: 18980602028; Email: wangziqiang@scu.edu.cn
      • Contact: Mingtian Wei, MD; Phone Number: 18980602400
      • Principal Investigator: Ziqiang Wang, MD
    • Chengdu, Sichuan, China, 610000
      • Recruiting
      • The Third People's Hospital of Chengdu
      • Contact: Liu Yan jun, MD; Phone Number: 15108402860
      • Principal Investigator: Liu Yan jun, MD
  • Yunnan
    • Kunming, Yunnan, China
      • Recruiting
      • The Third Affiliated Hospital of Kunming Medical University
      • Contact: Ping Liu, MD; Phone Number: +8615911552189

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2 cycles group; 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; oxaliplatin: 130 mg/m2 iv d 1, capecitabine: 1000 mg/m2 bid d 1-14, repeated at 3 week intervals
Other: 4 cycles group; 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; oxaliplatin: 130 mg/m2 iv d 1, capecitabine: 1000 mg/m2 bid d 1-14, repeated at 3 week intervals

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: West China Hospital
• Collaborators: Sun Yat-sen University; Peking University Cancer Hospital & Institute; Second Affiliated Hospital, School of Medicine, Zhejiang University; The First Affiliated Hospital of Zhengzhou University; The Affiliated Hospital Of Guizhou Medical University; Peking Union Medical College; Sichuan Provincial People's Hospital; Chengdu Fifth People's Hospital; Yunnan Cancer Hospital; GeneCast Biotechnology Co., Ltd.; Nanchong Central Hospital; The Third People's Hospital of Chengdu; Dazhou Central Hospital; Leshan People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2021
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): December 1, 2026

Study Registration Dates

• First Submitted: June 4, 2021
• First Submitted That Met QC Criteria: June 10, 2021
• First Posted (Actual): June 11, 2021

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 16, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: RC-CT-2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No