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Preoperative Chemoradiation Followed by Chemotherapy for Locally Advanced Rectal Cancer (PREPARE)

Primary Purpose

Rectal Neoplasms, Adenocarcinoma

Status
Unknown status
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Capecitabine Oxaliplatin
pelvic radiation capecitabine 5-fluorouracil
Sponsored by
National Cancer Center, Korea
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rectal Neoplasms focused on measuring rectal neoplasms, radiotherapy, Antineoplastic Agents

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • histologically confirmed adenocarcinoma of the rectum
  • distal margin of tumor located from 0 to 12 cm from anal verge measured by digital rectal examination

  • high risk clinical stage II or III in MRI (satisfying at least one of the followings)

    • circumferential resection margin < 1 mm involved
    • low-lying tumor below anal verge 3 cm
    • T3 > 5 mm extramural spread
    • T4 (involving surrounding structures or peritoneum)
    • cN2 (4 or more mixed signal intensity or irregularly bordered node or tumor deposit)
  • age 20 years or more
  • ECOG (Eastern Cooperative Oncology Group) performance status 0-2
  • No prior chemotherapy, radiotherapy to pelvis
  • Adequate bone marrow function
  • Adequate renal function
  • Adequate hepatic function
  • patients must sign the informed consent indicating that they were aware of the investigational nature of the study in keeping with the policy of the hospital

Exclusion Criteria:

  • malignant disease of the rectum other than adenocarcinoma or arisen from chronic inflammatory bowel disease
  • any unresected synchronous colon cancer
  • any distant metastases
  • intestinal obstruction or impending obstruction, but decompressing colostomy is permitted
  • any previous or concurrent malignancy withih 5 years other than non-melanoma skin cancer / in situ cancer of uterine cervix / early gastric cancer / thyroid cancer of low risk
  • any other morbidity or situation with relative contraindication for chemoradiotherapy
  • patients with history of significant gastric or small bowel resection, or malabsorption syndrome, or other lack of integrity of the upper gastrointestinal tract that may compromise the absorption of capecitabine
  • pregnant or lactating women or patients of childbearing potential not predicting adequate contraception

Sites / Locations

  • National Cancer Center
  • Seoul National University Bundang Hospital
  • Hallym University Sacred Heart Hospital
  • Gangneung Asan Hospital
  • Severance Hospital
  • Asan Medical Center
  • Chung-Ang University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

chemoradiation followed by CapOx

chemoradiation

Arm Description

preoperative chemoradiation 50.4Gy with capecitabine or 5-fluorouracil/leucovorin (pelvic radiation capecitabine 5-fluorouracil) followed by 2 cycles of chemotherapy (Capecitabine Oxaliplatin - CapOx) and surgery (total mesorectal excision)

preoperative chemoradiation 50.4Gy with capecitabine or 5-fluorouracil/leucovorin (pelvic radiation capecitabine 5-fluorouracil) followed by rest for 8 weeks and surgery (total mesorectal excision)

Outcomes

Primary Outcome Measures

downstaging rate
downstaging rate is defined as the proportion of patients with ypStage (pathologic stage after preoperative treatment) 0 or I (from pathologic findings after preoperative treatment and surgery) out of all patients who were assigned to each arm.

Secondary Outcome Measures

pathologic response
pathologic response is assessed by Dworak's grading system from postoperative specimen.
radiologic response rate
radiologic response will be assessed according to RECIST (Response Evaluation Criteria in Solid Tumors) guideline 1.1
toxicity profile
Toxicities or any adverse events during study treatment, surgery and follow-up period will be assessed according to NCI CTCAE (Common Terminology Criteria for Adverse Events) version 4.0
pattern of failure
if any recurrent lesion is noticed, anatomic sites of recurrent lesions and the date and the name of exam or imaging study (physical exam, CT or MRI…) will be recorded in case report form.
local control rate
Local recurrence is defined as tumor recurrence confined in radiation field (pelvic cavity). Cumulative incidence of local recurrence will be suggested.
relapse-free survival
Time from date of operation to date of recurrence of disease or deaths due to recurrence or progression of disease.
Disease-free survival
time from date of operation to date of recurrence of disease, a new occurrence of secondary colorectal cancer, a new occurrence of other malignancy, or deaths from any cause.
overall survival
time from date of operation to date of death due to any cause.
quality of life
quality of life will be measured with FACT-C

Full Information

First Posted
September 11, 2013
Last Updated
September 12, 2017
Sponsor
National Cancer Center, Korea
Collaborators
Korean Cancer Study Group
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1. Study Identification

Unique Protocol Identification Number
NCT01952951
Brief Title
Preoperative Chemoradiation Followed by Chemotherapy for Locally Advanced Rectal Cancer
Acronym
PREPARE
Official Title
A Randomized Phase II Trial of Preoperative Chemoradiation (Preop CRT) Followed by CapOx (Capecitabine Plus Oxaliplatin) Versus Preop CRT Alone for Locally Advanced Rectal Cancer (LARC)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Unknown status
Study Start Date
June 2014 (undefined)
Primary Completion Date
September 2017 (Actual)
Study Completion Date
December 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Cancer Center, Korea
Collaborators
Korean Cancer Study Group

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The current standard treatment of locally advanced rectal cancer (clinical stage II or III) is preoperative radiation with chemotherapy (CRT) followed by surgery. But this approach can be suboptimal for patients with high risk features (more deeply-seated tumor or many regional lymph nodes involved)that are associated with recurrence. This study test a hypothesis that CRT followed by chemotherapy before surgery can improve efficacy of preoperative treatment.
Detailed Description
Downstaging rate with CRT using fluoropyrimidine monotherapy is usually 30-40%.In MRI-defined high-risk patients, downstaging rate with conventional fluoropyrimidine-based monotherapy with radiation has not been shown. We assume that the downstaging rate of chemoradiation arm (control arm) would be 30%, and that addition of CapOx after CRT (experimental arm) may increase downstaging rate 30% to 50%. A sample size of 52 patients per group is needed have 85% power to detect downstaging rate = 50% as compared to 30% with type I error rate of 15%. We will perform one interim futility analysis when half of the patients are recruited and evaluated for the primary endpoint. O'Brien-Fleming boundary will be considered. Therefore, when 26 patients per arm are evaluated, the interim futility analysis will be performed, and when the Z score at the interim is less than -0.09192 (one-sided p-value greater than 0.5366192), the study will be stopped for futility. Considering 5% follow-up loss, a sample size of 55 per arm (a total of 110 patients) will be studied.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Neoplasms, Adenocarcinoma
Keywords
rectal neoplasms, radiotherapy, Antineoplastic Agents

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
110 (Actual)

8. Arms, Groups, and Interventions

Arm Title
chemoradiation followed by CapOx
Arm Type
Experimental
Arm Description
preoperative chemoradiation 50.4Gy with capecitabine or 5-fluorouracil/leucovorin (pelvic radiation capecitabine 5-fluorouracil) followed by 2 cycles of chemotherapy (Capecitabine Oxaliplatin - CapOx) and surgery (total mesorectal excision)
Arm Title
chemoradiation
Arm Type
Active Comparator
Arm Description
preoperative chemoradiation 50.4Gy with capecitabine or 5-fluorouracil/leucovorin (pelvic radiation capecitabine 5-fluorouracil) followed by rest for 8 weeks and surgery (total mesorectal excision)
Intervention Type
Drug
Intervention Name(s)
Capecitabine Oxaliplatin
Other Intervention Name(s)
Xeloda, Oxalitin
Intervention Description
after completion of chemoradiation, two cycles of capecitabine (850mg/m2 twice daily from D1 evening to D15 morning) and oxaliplatin (100mg/m2 on D1) will be administered every 3 weeks.
Intervention Type
Radiation
Intervention Name(s)
pelvic radiation capecitabine 5-fluorouracil
Other Intervention Name(s)
preoperative chemoradiation, xeloda
Intervention Description
50.4Gy of pelvic radiation with capecitabine or 5-fluorouracil
Primary Outcome Measure Information:
Title
downstaging rate
Description
downstaging rate is defined as the proportion of patients with ypStage (pathologic stage after preoperative treatment) 0 or I (from pathologic findings after preoperative treatment and surgery) out of all patients who were assigned to each arm.
Time Frame
expected average of 15 weeks after start of study treatment
Secondary Outcome Measure Information:
Title
pathologic response
Description
pathologic response is assessed by Dworak's grading system from postoperative specimen.
Time Frame
expected average of 15 weeks after start of study treatment
Title
radiologic response rate
Description
radiologic response will be assessed according to RECIST (Response Evaluation Criteria in Solid Tumors) guideline 1.1
Time Frame
expected average of 14 weeks after start of study treatment
Title
toxicity profile
Description
Toxicities or any adverse events during study treatment, surgery and follow-up period will be assessed according to NCI CTCAE (Common Terminology Criteria for Adverse Events) version 4.0
Time Frame
expected average of 35 weeks after start of study treatment
Title
pattern of failure
Description
if any recurrent lesion is noticed, anatomic sites of recurrent lesions and the date and the name of exam or imaging study (physical exam, CT or MRI…) will be recorded in case report form.
Time Frame
3 years after surgery
Title
local control rate
Description
Local recurrence is defined as tumor recurrence confined in radiation field (pelvic cavity). Cumulative incidence of local recurrence will be suggested.
Time Frame
3 years after surgery
Title
relapse-free survival
Description
Time from date of operation to date of recurrence of disease or deaths due to recurrence or progression of disease.
Time Frame
3 years after surgery
Title
Disease-free survival
Description
time from date of operation to date of recurrence of disease, a new occurrence of secondary colorectal cancer, a new occurrence of other malignancy, or deaths from any cause.
Time Frame
3 years after surgery
Title
overall survival
Description
time from date of operation to date of death due to any cause.
Time Frame
3 years after surgery
Title
quality of life
Description
quality of life will be measured with FACT-C
Time Frame
before study treatment, 7 weeks after completion of chemoradiation, and at 4 weeks after surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: histologically confirmed adenocarcinoma of the rectum distal margin of tumor located from 0 to 12 cm from anal verge measured by digital rectal examination high risk clinical stage II or III in MRI (satisfying at least one of the followings) circumferential resection margin < 1 mm involved low-lying tumor below anal verge 3 cm T3 > 5 mm extramural spread T4 (involving surrounding structures or peritoneum) cN2 (4 or more mixed signal intensity or irregularly bordered node or tumor deposit) age 20 years or more ECOG (Eastern Cooperative Oncology Group) performance status 0-2 No prior chemotherapy, radiotherapy to pelvis Adequate bone marrow function Adequate renal function Adequate hepatic function patients must sign the informed consent indicating that they were aware of the investigational nature of the study in keeping with the policy of the hospital Exclusion Criteria: malignant disease of the rectum other than adenocarcinoma or arisen from chronic inflammatory bowel disease any unresected synchronous colon cancer any distant metastases intestinal obstruction or impending obstruction, but decompressing colostomy is permitted any previous or concurrent malignancy withih 5 years other than non-melanoma skin cancer / in situ cancer of uterine cervix / early gastric cancer / thyroid cancer of low risk any other morbidity or situation with relative contraindication for chemoradiotherapy patients with history of significant gastric or small bowel resection, or malabsorption syndrome, or other lack of integrity of the upper gastrointestinal tract that may compromise the absorption of capecitabine pregnant or lactating women or patients of childbearing potential not predicting adequate contraception
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sun Young Kim, MD
Organizational Affiliation
Asan Medical Center
Official's Role
Study Chair
Facility Information:
Facility Name
National Cancer Center
City
Goyang
State/Province
Gyeonggi-do
ZIP/Postal Code
410-769
Country
Korea, Republic of
Facility Name
Seoul National University Bundang Hospital
City
Seongnam
State/Province
Gyeonggi-do
ZIP/Postal Code
13620
Country
Korea, Republic of
Facility Name
Hallym University Sacred Heart Hospital
City
Anyang
Country
Korea, Republic of
Facility Name
Gangneung Asan Hospital
City
Gangneung
Country
Korea, Republic of
Facility Name
Severance Hospital
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Chung-Ang University Hospital
City
Seoul
ZIP/Postal Code
06973
Country
Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
29976501
Citation
Kim SY, Joo J, Kim TW, Hong YS, Kim JE, Hwang IG, Kim BG, Lee KW, Kim JW, Oh HS, Ahn JB, Zang DY, Kim DY, Oh JH, Baek JY. A Randomized Phase 2 Trial of Consolidation Chemotherapy After Preoperative Chemoradiation Therapy Versus Chemoradiation Therapy Alone for Locally Advanced Rectal Cancer: KCSG CO 14-03. Int J Radiat Oncol Biol Phys. 2018 Jul 15;101(4):889-899. doi: 10.1016/j.ijrobp.2018.04.013. Epub 2018 Apr 12.
Results Reference
derived

Learn more about this trial

Preoperative Chemoradiation Followed by Chemotherapy for Locally Advanced Rectal Cancer

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