A Trial of High Intensity Versus Low Intensity Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

An Open Label, Randomized, Multi-center, Phase II/III Trial of High Intensity Versus Low Intensity Neoadjuvant Chemoradiotherapy With Intensity-modified Radiation Therapy (IMRT) in Local Advanced Rectal Cancer

Neoadjuvant chemoradiotherapy (CRT) has been the standard therapy for local advanced rectal cancer. Pathological complete response (pCR) is an important prognostic factor for local control and survival. A high intensity CRT increases not only the pCR rate, but also toxicity, especially diarrhea. Compared with traditional RT technique, intensity-modified radiation therapy (IMRT) can decrease the toxicity of diarrhea because of low volume of high dose for small bowel. Therefore, IMRT technique provides an opportunity to improve the dose intensity of neoadjuvant CRT. The investigators hypothesize that a higher treatment dose induces a high rate of pCR and design a two-arm trial. in this trial, low intensity CRT includes the whole pelvic irradiation of 50Gy together with Oxaliplatin and Capecitabine weekly. While in high intensity group, additional concomitant 5Gy for primary tumor and a cycle of Xelox are prescribed. All patients will receive a total mesorectal excision (TME) 8 weeks after CRT.

Study Overview

• Status: Unknown
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: Oxaliplatin; Drug: Capecitabine; Radiation: Radiotherapy; Procedure: Surgery

• Study Type: Interventional
• Enrollment (Anticipated): 240
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Cancer Hospital, FuDan University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients with rectal adenocarcinoma
• Clinical staged T3/4 or any node-positive disease
• Age: 18-75 years
• Karnofsky Performance Status > 80
• Adequate bone marrow reserve, renal and hepatic functions
• Without previous antitumoural chemotherapy
• No evidence of metastatic disease
• Written informed consent before randomization

Exclusion Criteria:

• Previous pelvis radiotherapy.
• Previous antitumoural chemotherapy
• Clinically significant internal disease

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: High intensity group; (RT 55Gy + CapOx) + a cycle of Xelox + Surgery	Drug: Oxaliplatin; CRT:50mg/m2,IV,weekly*5 cycle CT: 130mg/m2,IV,d1,q 21 day; Drug: Capecitabine; CRT:625mg/m2,bid,d1-5,q week RT:1000mg/m2,bid,d1-14,q 3 weeks; Radiation: Radiotherapy; High intensity group:55Gy Low intensity group:50Gy; Procedure: Surgery; Lower anterior resection or abdominoperineal resection
Active Comparator: Low instensity group; (RT 50Gy + CapOx) + Surgery	Drug: Oxaliplatin; CRT:50mg/m2,IV,weekly*5 cycle CT: 130mg/m2,IV,d1,q 21 day; Drug: Capecitabine; CRT:625mg/m2,bid,d1-5,q week RT:1000mg/m2,bid,d1-14,q 3 weeks; Radiation: Radiotherapy; High intensity group:55Gy Low intensity group:50Gy; Procedure: Surgery; Lower anterior resection or abdominoperineal resection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the rate of pathological complete response (pCR)	within 14days after surgery
toxicity	every week during radiotherapy

Secondary Outcome Measures

Outcome Measure	Time Frame
local recurrence	every half year after surgery
disease-free survival	every half year after surgery
overall survival	every half year after surgery

Collaborators and Investigators

• Sponsor: Fudan University
• Collaborators: Zhejiang Cancer Hospital; RenJi Hospital; First People Hospital of Zhejiang

Publications and helpful links

General Publications

• Wang J, Guan Y, Gu W, Yan S, Zhou J, Huang D, Tong T, Li C, Cai S, Zhang Z, Zhu J. Long-course neoadjuvant chemoradiotherapy with versus without a concomitant boost in locally advanced rectal cancer: a randomized, multicenter, phase II trial (FDRT-002). Radiat Oncol. 2019 Nov 29;14(1):215. doi: 10.1186/s13014-019-1420-z.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): March 1, 2012
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: February 5, 2010
• First Submitted That Met QC Criteria: February 8, 2010
• First Posted (Estimate): February 9, 2010

Study Record Updates

• Last Update Posted (Estimate): March 14, 2012
• Last Update Submitted That Met QC Criteria: March 12, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: Neoadjuvant chemotherapy; intensity-modulated radiation therapy; locally advanced rectal cancer; pathological complete response
• 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; Oxaliplatin
• Other Study ID Numbers: FDRT-002