- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01952951
Preoperative Chemoradiation Followed by Chemotherapy for Locally Advanced Rectal Cancer (PREPARE)
September 12, 2017 updated by: Sun Young Kim, National Cancer Center, Korea
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)
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.
Study Overview
Status
Unknown
Conditions
Intervention / 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.
Study Type
Interventional
Enrollment (Actual)
110
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Anyang, Korea, Republic of
- Hallym University Sacred Heart Hospital
-
Gangneung, Korea, Republic of
- Gangneung Asan Hospital
-
Seoul, Korea, Republic of, 03722
- Severance Hospital
-
Seoul, Korea, Republic of, 05505
- Asan Medical Center
-
Seoul, Korea, Republic of, 06973
- Chung-Ang University Hospital
-
-
Gyeonggi-do
-
Goyang, Gyeonggi-do, Korea, Republic of, 410-769
- National Cancer Center
-
Seongnam, Gyeonggi-do, Korea, Republic of, 13620
- Seoul National University Bundang Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
20 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: chemoradiation followed by CapOx
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)
|
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.
Other Names:
50.4Gy of pelvic radiation with capecitabine or 5-fluorouracil
Other Names:
|
Active Comparator: chemoradiation
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)
|
50.4Gy of pelvic radiation with capecitabine or 5-fluorouracil
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
downstaging rate
Time Frame: expected average of 15 weeks after start of study treatment
|
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.
|
expected average of 15 weeks after start of study treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
pathologic response
Time Frame: expected average of 15 weeks after start of study treatment
|
pathologic response is assessed by Dworak's grading system from postoperative specimen.
|
expected average of 15 weeks after start of study treatment
|
radiologic response rate
Time Frame: expected average of 14 weeks after start of study treatment
|
radiologic response will be assessed according to RECIST (Response Evaluation Criteria in Solid Tumors) guideline 1.1
|
expected average of 14 weeks after start of study treatment
|
toxicity profile
Time Frame: expected average of 35 weeks after start of study treatment
|
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
|
expected average of 35 weeks after start of study treatment
|
pattern of failure
Time Frame: 3 years after surgery
|
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.
|
3 years after surgery
|
local control rate
Time Frame: 3 years after surgery
|
Local recurrence is defined as tumor recurrence confined in radiation field (pelvic cavity).
Cumulative incidence of local recurrence will be suggested.
|
3 years after surgery
|
relapse-free survival
Time Frame: 3 years after surgery
|
Time from date of operation to date of recurrence of disease or deaths due to recurrence or progression of disease.
|
3 years after surgery
|
Disease-free survival
Time Frame: 3 years after surgery
|
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.
|
3 years after surgery
|
overall survival
Time Frame: 3 years after surgery
|
time from date of operation to date of death due to any cause.
|
3 years after surgery
|
quality of life
Time Frame: before study treatment, 7 weeks after completion of chemoradiation, and at 4 weeks after surgery
|
quality of life will be measured with FACT-C
|
before study treatment, 7 weeks after completion of chemoradiation, and at 4 weeks after surgery
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Chair: Sun Young Kim, MD, Asan Medical Center
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2014
Primary Completion (Actual)
September 1, 2017
Study Completion (Anticipated)
December 1, 2019
Study Registration Dates
First Submitted
September 11, 2013
First Submitted That Met QC Criteria
September 25, 2013
First Posted (Estimate)
September 30, 2013
Study Record Updates
Last Update Posted (Actual)
September 13, 2017
Last Update Submitted That Met QC Criteria
September 12, 2017
Last Verified
September 1, 2017
More Information
Terms related to this study
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
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Fluorouracil
- Capecitabine
- Oxaliplatin
Other Study ID Numbers
- KCSG CO14-03
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Adenocarcinoma
-
Criterium, Inc.University of Colorado, Denver; NovartisTerminatedPancreatic Adenocarcinoma | Gastric Adenocarcinoma | Cholangiocarcinoma | Esophageal Adenocarcinoma | Colorectal Adenocarcinoma | Hepatocellular AdenocarcinomaUnited States
-
University of ChicagoCompletedGastric Adenocarcinoma | Esophageal Adenocarcinoma | Gastroesophageal Junction AdenocarcinomaUnited States
-
Weill Medical College of Cornell UniversityMerck Sharp & Dohme LLC; Oncolys BioPharma IncNot yet recruitingGastric Adenocarcinoma | Esophageal Adenocarcinoma | Gastroesophageal Junction AdenocarcinomaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)RecruitingClinical Stage III Gastric Cancer AJCC v8 | Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 | Clinical Stage IV Gastric Cancer AJCC v8 | Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8 | Metastatic Gastric Adenocarcinoma | Metastatic Gastroesophageal Junction... and other conditionsUnited States, Puerto Rico
-
Roswell Park Cancer InstituteUnited States Department of DefenseRecruitingClinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 | Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8 | Metastatic Gastroesophageal Junction Adenocarcinoma | Unresectable Gastroesophageal Junction Adenocarcinoma | Locally Advanced Gastroesophageal Junction... and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingGastroesophageal Junction Adenocarcinoma | Clinical Stage II Esophageal Adenocarcinoma AJCC v8 | Clinical Stage IIA Esophageal Adenocarcinoma AJCC v8 | Clinical Stage III Esophageal Adenocarcinoma AJCC v8 | Pathologic Stage II Esophageal Adenocarcinoma AJCC v8 | Pathologic Stage IIA Esophageal... and other conditionsUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)RecruitingPancreas Adenocarcinoma | Locally Advanced Pancreatic Adenocarcinoma | Borderline Resectable Pancreatic AdenocarcinomaUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Uterine Corpus Carcinoma | Endometrial Clear Cell Adenocarcinoma | Endometrial Serous Adenocarcinoma | Endometrial Undifferentiated Carcinoma | Endometrial Adenocarcinoma | Endometrial Transitional Cell Carcinoma | Endometrial Mucinous Adenocarcinoma | Endometrial Mixed Adenocarcinoma | Endometrial...United States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Uterine Corpus Carcinoma | Endometrial Clear Cell Adenocarcinoma | Endometrial Serous Adenocarcinoma | Endometrial Undifferentiated Carcinoma | Endometrial Adenocarcinoma | Endometrial Transitional Cell Carcinoma | Endometrial Mucinous Adenocarcinoma | Endometrial Mixed Adenocarcinoma | Endometrial...United States
-
National Cancer Institute (NCI)Not yet recruitingClinical Stage III Gastric Cancer AJCC v8 | Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 | Clinical Stage IV Gastric Cancer AJCC v8 | Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8 | Metastatic Gastric Adenocarcinoma | Metastatic Gastroesophageal Junction... and other conditions
Clinical Trials on Capecitabine Oxaliplatin
-
Samsung Medical CenterNational Cancer Center, Korea; Asan Medical Center; Chonnam National University... and other collaboratorsCompletedColorectal CancerKorea, Republic of
-
Hebei Medical UniversityCompletedGastroesophageal Junction AdenocarcinomaChina
-
Hebei Medical UniversityUnknownGastric Cancer | Liver MetastasisChina
-
Samsung Medical CenterCompleted
-
AIO-Studien-gGmbHiOMEDICO AGTerminated
-
Peking UniversityTaiho Pharmaceutical Co., Ltd.Unknown
-
Hebei Medical UniversityUnknownGastroesophageal Junction AdenocarcinomaChina
-
Hebei Medical UniversityUnknownLiver Metastasis | HER-2 Positive Gastric CancerChina
-
University of Southern CaliforniaBristol-Myers Squibb; Sanofi; Roche Global DevelopmentUnknownGastric Cancer | Esophageal CancerUnited States
-
Royal Marsden NHS Foundation TrustCompletedColorectal CancerUnited Kingdom