Induction Chemotherapy for MRF-negative, Moderate-risk, Resectable Middle and Low Rectal Cancer

Phase 2

• Conditions: Rectal Cancer
• Interventions: Drug: Oxaliplatin and capecitabine; Procedure: Total Mesorectal Excision

• Registration Number: NCT04296240
• Lead Sponsor: Peking University Cancer Hospital & Institute

Brief Summary

This study is designed to test the Safety and efficacy of induction and individualized neoadjuvant chemotherapy based on oxaliplatin combined with fluorouracil for MRF-negative, moderate-risk and initially resectable middle and low rectal cancer.

Detailed Description

Preoperative chemoradiation has become standard treatment for stage 2/3 rectal cancer. But for moderate-risk rectal cancer patients, whether neoadjuvant chemotherapy followed with total mesorectal excision is adequate for local control is still unknown. The necessity of preoperative radiotherapy for these patients needs further exploration.

This study is a single-arm, single-center, prospective, phase II clinical study. It is designed to test the efficacy and safety of neoadjuvant chemotherapy for MRF-negative, moderate-risk and initially resectable middle and low rectal cancer.

In this study, patients with MRI defined moderate-risk rectal cancer will receive a three-month neoadjuvant chemotherapy based on Oxaliplatin combined with Fluorouracil(CapeOX,SOX,mFOLFOX6,etc.) and Total mesorectal excision.

Primary Endpoint is pCR rate.Secondary endpoint concludes toxic reactions of neoadjuvant chemotherapy, Incidence of surgical complications and three-year disease-free survival (DFS).

This study is designed to recruit 119 patients in all.

Study Timeline

• Study Start: 2019-03-01
• Study First Submitted: 2019-08-26
• Status Verified: 2020-03
• Study First Submitted QC: 2020-03-03
• Last Update Submitted: 2020-03-03
• Study First Posted: 2020-03-05
• Last Update Posted: 2020-03-05
• Primary Completion: 2021-04
• Study Completion: 2024-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 119

Inclusion Criteria

• • Age ≥18 years and ≤80 years

  • ECOG Performance status 0-1

  • Histologically confirmed diagnosis of adenocarcinoma of the rectum

  • The distance from down verge of tumor to anal-rectal junction (ARJ) ≤8cm based on MRI, or ≤12cm based on sigmoidoscopy;

  • Clinical Stage based on MRI

    1. mrMRF(-)
    2. T3c/T3d/T4a, anyN, or T3bN+

  • No evidence of distant metastases

  • No prior pelvic radiation therapy

  • No prior chemotherapy or surgery for rectal cancer

  • No active infections requiring systemic antibiotic treatment

  • ANC > 1.5 cells/mm3, HGB > 10.0 g/dL, PLT > 100,000/mm3, total bilirubin ≤ 1.5 x ULN, AST≤ 3 x ULN, ALT ≤ 3 x ULN.

  • Patients must read, agree to, and sign a statement of Informed Consent prior to participation in this study.

Exclusion Criteria

• • Recurrent rectal cancer

  • Primary unresectable rectal cancer. A tumor is considered unresectable when invading adjacent organs and an en-bloc resection will not achieve negative margins.
  • The pathological grade was Grade 4, i.e. mucus, signet ring or undifferentiated cancer.
  • Creatinine level greater than 1.5 times the upper limit of normal.
  • Patients who have received prior pelvic radiotherapy.
  • Patients who are unable to undergo an MRI.
  • Patients with a history of a prior malignancy within the past 5 years, except for adequately treated basal cell or squamous cell skin cancer.
  • Patients with a history of any arterial thrombotic event within the past 6 months. This includes angina (stable or unstable), MI, TIA, or CVA.
  • Other Anticancer or Experimental Therapy.
  • Women who are pregnant or breast-feeding.
  • Patients with any other concurrent medical or psychiatric condition or disease which would make them inappropriate candidates for entry into this study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Neoadjuvant chemotherapy	Oxaliplatin and capecitabine	Oxaliplatin 130mg/m2 d1 and Capecitabine 1250mg/m2 bid1-14 or other fluorouracils, every 21 or 14 days for 2 to 4 cycles, and efficacy evaluation every 2 cycles;
Neoadjuvant chemotherapy	Total Mesorectal Excision	Oxaliplatin 130mg/m2 d1 and Capecitabine 1250mg/m2 bid1-14 or other fluorouracils, every 21 or 14 days for 2 to 4 cycles, and efficacy evaluation every 2 cycles;

Primary Outcome Measures

Name	Time	Method
pathologic complete response rate	30 days	the number of patients with pCR divided by the total number of patients

Secondary Outcome Measures

Name	Time	Method
surgical complication rate	30 days after the operation	rate of patients who had surgical complications during the perioperative period
Toxicity of neoadjuvant chemotherapy	4 months	category and grade of adverse event during neoadjuvant chemotherapy
3 year disease-free survival	three years after the enrollment	cumulative rate of survival without cancer after 3 years follow up

Trial Locations

Locations (1)

Beijing Cancer Hospital; 🇨🇳 Beijing, Beijing, China