Modified Sandwich Therapeutic Regimen for Locally Advanced Rectal Cancer

Single Arm and Phase II Clinical Trial of a Sandwich Regimen as XELOX Regimen and Capecitabine Alternate Administration Combined With Preoperative Intensity Modulated Radiation Therapy for pMMR Locally Advanced Rectal Cancer

In the treatment of locally advanced rectal cancer, the short-term and long-term efficacy of the traditional sandwich regimen has not reached satisfactory efficacy. For this reason, the concept of reducing the dose of postoperative chemotherapy or directly moving forward the full amount of postoperative chemotherapy was proposed, which is called total neoadjuvant therapy (TNT). However, TNT also includes the high toxicity of oxaliplatin in the whole process and the long time interval between the end of radiotherapy and the operation, which leads to fibrosis of the surrounding tissue, which increases the difficulty of surgical resection and makes it difficult to ensure good surgical specimen quality. In addition to this, there are issues that may increase the risk of potential disease progression in patients with poor treatment withdrawal. Therefore, appropriately reducing the intensity of chemotherapy and controlling the total duration of preoperative neoadjuvant therapy during radiotherapy is expected to alleviate the side effects of neoadjuvant therapy. Here, the investigators synthesized the characteristics of TNT and sandwich regimens and proposed a XELOX regimen and capecitabine alternate administration combined with preoperative intensity modulated radiation therapy.

Study Overview

• Status: Recruiting
• Conditions: Advanced Rectal Cancer
• Intervention / Treatment: Drug: XELOX; Drug: Capecitabine monotherapy; Radiation: Radiation

• Study Type: Interventional
• Enrollment (Estimated): 121
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhenhai Lu, Prof; Phone Number: +862087343584; Email: luzhh@sysucc.org.cn
• Study Contact Backup: Name: Jianhong Peng, M.D; Phone Number: +862087343584; Email: pengjh@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Zhenhai Lu
      • Sub-Investigator: Zhifan Zeng, M.D
      • Contact: Zhenhai Lu, Prof; Phone Number: +86 20 87343584; Email: luzhh@sysucc.org.cn
      • Contact: Jianhong Peng, Doctor; Phone Number: +86 20 87343584; Email: pengjh@sysucc.org.cn
      • Sub-Investigator: Xiaojun Wu, M.D
      • Sub-Investigator: Junzhong Lin, M.D
      • Sub-Investigator: Rongxin Zhang, M.D
      • Sub-Investigator: Weiwei Xiao, M.D
      • Sub-Investigator: Yujing Fang, Ph.D
      • Sub-Investigator: Fulong Wang, M.D
      • Sub-Investigator: Jianhong Peng, M.D
      • Sub-Investigator: Yuan Li, M.D
      • Sub-Investigator: Qingjian Ou, M.D
      • Sub-Investigator: Weili Zhang, M.D
      • Sub-Investigator: Jiali Chen, M.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Pathological confirmed rectal adenocarcinoma.

Clinical stage T3-4 or T any N1.With or without MRF positivity, with or without EMVI positivity, R0 resection is estimated.

No metastasis

No signs of intestinal obstruction; or intestinal obstruction has been relieved after proximal colostomy surgery.

Age ranged from 18 to 75

No previous radiotherapy，surgery and chemotherapy.

Exclusion Criteria:

Multiple primary tumor

Cachexy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Sandwich Regimen; All rectal patients in this group will receive standard surgical resection.

Drug: XELOX; Starting from the first day of radiotherapy (set as day 0), the patient received a total of 4 courses of XELOX chemotherapy on days -42, -21, 42, and 63, including oxaliplatin 130 mg/m2, intravenous administration, d1, repeat every 3 weeks; and capecitabine 1000mg/m2, twice daily, d1-d14, repeat every 3 weeks.; Drug: Capecitabine monotherapy; During radiotherapy (Monday to Friday), capecitabine was administered at 1650 mg/m2/d, twice a day.; Radiation: Radiation; The TV is expanded by 6-7mm to form PTV1, and the CTV is expanded by 6-7mm to form PTV2. The dose of PTV1 was 50Gy/25 times/35 days, and the dose of PTV2 was 45Gy/25 times/35 days, 5 times/week for a total of 5 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of pCR	rate of pathological complete remission	One week after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	overall survival	5 years
DFS	Disease free survival	3 years

Collaborators and Investigators

• Sponsor: Zhen-Hai Lu

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2022
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: January 22, 2022
• First Submitted That Met QC Criteria: February 7, 2022
• First Posted (Actual): February 8, 2022

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Rectal cancer; neoadjuvant chemoradiotherapy; optimization
• 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; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: 2021-FXY-494-Department of CRC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No