Two-week Course Versus Conventionally Fractionated Chemoradiotherapy in Rectal Cancer

Two-Week COurse Versus Conventionally Fractionated Preoperative Chemoradiotherapy In Locally Advanced Rectal Cancer (TwoArc Trial): A Phase III Randomized Clinical Trial

The investigators compare two-week course of chemoradiation (33 Gy in 10 fractions with oral capecitabine) and conventional chemoradiation (50.4 Gy in 28 fractions with 5-FU and leucovorin) in this randomized trial.

Study Overview

• Status: Unknown
• Conditions: Recurrence; Toxicity; Response to Toxin
• Intervention / Treatment: Radiation: Two-week course of radiation; Drug: Two-week course of radiation

Detailed Description

1.1 experimental arm Two-week course concurrent chemoradiotherapy

• Radiotherapy, 33 Gy/10 fractions for 2 weeks

  ↓↓↓↓↓ ↓↓↓↓↓ Radical surgery 6 weeks after completion of chemoradiotherapy D1----------------------D12

• Capecitabine 825 mg/m2, twice daily

1.2 control arm

Standard concurrent chemoradiotherapy (CRT)

• Radiotherapy, 50.4 Gy/28 fractions for 6 weeks

  ↓↓↓↓↓ ↓↓↓↓↓ ↓↓↓↓↓ ↓↓↓↓↓ ↓↓↓↓↓ ↓↓↓ Radical surgery D1--------------------------------------------------------------------------D38

• Bolus 5-FU, 400 mg/ m2 and leucovorin, 20 mg/ m2 during week 1 and 5
• Capecitabine, 825 mg/ m2, bid

• Study Type: Interventional
• Enrollment (Anticipated): 370
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Suwon, Korea, Republic of
    • Recruiting
    • Lee Jong Hoon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. histologically confirmed adenocarcinoma;
2. distal margin of the tumor located < 10 cm from the anal verge;
3. cT3-4N0-2 classification as determined by magnetic resonance imaging (MRI) and/or endorectal ultrasonography (EUS);
4. no evidence of distant metastasis;
5. Karnofsky performance score over 70;
6. adequate bone marrow, liver, and renal function (leucocytes >4000/mm3, hemoglobin >10 g/dL, platelets >100,000/mm3; serum bilirubin <1.5 mg/dL, serum transaminase <2.5 times the upper normal limit; serum creatinine <1.5 mg/dL).

Exclusion Criteria:

1. Metastatic disease
2. No complete resection of tumor (R2)

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: Two-week course arm; Experimental arm receive 33 Gy in 10 fractions of radiation for 2 weeks with oral capecitabine. Two-week course of radiation, 33 Gy/10 fx and oral capecitabine, 825 mg/m2, bid	Radiation: Two-week course of radiation; 33 Gy in 10 fractions for 2 weeks; Other Names: experimental arm; Drug: Two-week course of radiation; oral capecitabine, 825mg/m2, bid; Other Names: experimental arm
No Intervention: Conventional arm; conventionally fractionated radiation of 50.4 Gy/28 fx and 5-FU, 500 mg/m2 and leucovorin, 20 mg/m2 for 5 days, monthly or Capecitabine, 825 mg/m2, bid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor response from stage II-III to stage 0-I	Downstaging rate was evaluated by comparing pre-clinical and post-CRT pathological stages, and downstaging was defined as ypStage 0-I (ypT0-2N0M0)	from clinical staging time to radical surgery date (about 3 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity (acute and chronic)	During the course of radiotherapy, patients were evaluated weekly to assess acute toxicity. Patients were also followed 2 and 4 weeks after completion of radiotherapy and until 3 years after curative surgery to assess toxicity. Toxicity are assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0).	from radiation start to 3 years after radical surgery
Recurrence and survival		3-year recurrence-free survival and 3-year overall survival

Collaborators and Investigators

• Sponsor: Jong Hoon Lee
• Investigators: Principal Investigator: Jong Hoon Lee, MD, St. Vincent's Hospital, The Catholic University of Kora

Publications and helpful links

General Publications

• Lee JH, Kim JG, Oh ST, Lee MA, Chun HG, Kim DY, Kim TH, Kim SY, Baek JY, Park JW, Oh JH, Park HC, Choi DH, Park YS, Kim HC, Chie EK, Jang HS. Two-week course of preoperative chemoradiotherapy followed by delayed surgery for rectal cancer: a phase II multi-institutional clinical trial (KROG 11-02). Radiother Oncol. 2014 Jan;110(1):150-4. doi: 10.1016/j.radonc.2013.11.013. Epub 2014 Jan 7.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Anticipated): July 1, 2019
• Study Completion (Anticipated): July 1, 2021

Study Registration Dates

• First Submitted: June 17, 2015
• First Submitted That Met QC Criteria: June 24, 2015
• First Posted (Estimate): June 29, 2015

Study Record Updates

• Last Update Posted (Actual): June 5, 2017
• Last Update Submitted That Met QC Criteria: June 1, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: recurrence; toxicity; rectum; tumor response; chemoradiotherpy
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Recurrence
• Other Study ID Numbers: TwoArc trial

Plan for Individual participant data (IPD)

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