Condition category
Cancer
Date applied
05/07/2016
Date assigned
25/07/2016
Last edited
22/07/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Rectal cancer is a type of cancer that develops in the large bowel. I’ts called rectal cancer because of its position within the length of the bowel. Patients that have been diagnosed with locally advanced rectal cancer (that is, cancer that has grown through the wall of the rectum but not yet spread to the lymph nodes) are often treated with both chemotherapy and radiation (chemoradiation) before they considered for surgery. This study is investigating the success of a particular treatment; namely a high-dose of a drug called tegafur-uracil together with another one called leucovorin in addition to radiation therapy for patients before they undergo surgery for locally advanced rectal cancer.

Who can participate?
Adults with locally advanced rectal cancer that have not yet been treated with chemotherapy.

What does the study involve?
All participants are given radiotherapy plus chemotherapy treatment with tegafur-uracil (400mg/m2/day) and leucovorin (90mg/day). The drugs are given to each patient throughout their radiation treatment. All participants are then followed up to see whether their cancer has responded to the treatment, whether they suffered any ill effects from the treatment, how long it is before the cancer reoccurs. Overall survival rate data is also collected. Participants are also asked to give blood samples for pharmacogenetic analysis to see whether people with certain genetic profiles are more likely to be successfully treated than others.

What are the possible benefits and risks of participating?
Participants are given the treatment without change for the duration of the study. There could be some adverse effects from taking the high dose of tegafur-uracil.

Where is the study run from?
National Cancer Center, Goyang (South Korea)

When is the study starting and how long is it expected to run for?
October 2008 to November 2012

Who is funding the study?
National Cancer Center, Goyang (South Korea)

Who is the main contact?
Ms Hyun Mi Kim
ncccolonco@hanmail.net

Trial website

Contact information

Type

Scientific

Primary contact

Ms Hyun Mi Kim

ORCID ID

Contact details

323 Ilsan-ro
Ilsandong-gu
Goyang
10408
Korea
South
82-31-920-1145
ncccolonco@hanmail.net

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

NCC-CTS-08-358

Study information

Scientific title

A phase II study of preoperative chemoradiation with UFT-E plus leucovorin and the translational research for detection of predictive markers in the patients with locally advanced resectable rectal cancer

Acronym

Study hypothesis

Pathologic complete response rate with enteric coated tegafur-uracil(UFT-E) and leucovorin for locally advanced rectal cancer (cT3-4NxM0) would be more than 20%

Ethics approval

Institutional Review Boards of National Cancer Center, Korea, 20/10/2008, ref: NCCCTS-08-358

Study design

Single-arm phase II study

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

No participant information sheet available

Condition

Locally advanced rectal cancer (cT3-4, Nx, M0)

Intervention

This is a single-arm, phase II study of preoperative radiotherapy (RT) with enteric-coated tegafur-uracil (UFT-E) and leucovorin.
1. Radiotherapy (RT): started within 14 days after screening and obtaining informed consent. RT to whole pelvis at a dose of 45 Gy in 25 fractions, followed by 5.4 Gy in a three-fraction boost to the primary tumor.
2. Enteric-coated tegafur-uracil (UFT-E) : 400 mg/m2 of tegafur divided into three daily doses without drug holidays during RT. - Since each package of UFT-E contains 500 mg of granules that correspons to 100 mg of tegafur, the recommended dosing schedule according to body surface area (BSA) are as follows:
2.1. BSA ≤ 1.37 m2: 2, 2, and 1 packages an hour after breakfast, lunch and dinner, respectively
2.2. BSA 1.38 m2 – 1.62 m2: 2, 2, and 2 packages; BSA 1.63 m2 – 1.87 m2: 3, 2, and 2 packages
2.3. BSA ³ 1.88 m2: 3, 3, and 2 packages
3. Leucovorin: 30mg (2 tablets) p.o. With each UFF-E dose, corresponding to a total daily dose of 90 mg
4. Surgery: planned within 6 ± 2 weeks of the completion of RT. Total mesorectal excision is the first-choice surgical treatment

Intervention type

Drug

Phase

Phase II

Drug names

1. Enteric-coated tefagur-uracil
2. Leucovorin

Primary outcome measures

Pathologic complete response by Dworak’s classification, assessed with surgical specimen (including primary tumor and regional lymph nodes) derived from total mesorectal excision.

Dworak’s classification:
Grade 0 no regression
Grade 1 dominant tumor mass with obvious fibrosis and/or vasculopathy Grade 2 dominantly fibrotic changes with few tumor cells or groups (easy to find)
Grade 3 very few (difficult to find microscopically) tumor cells in fibrotic tissue with or without mucous substance
Grade 4 no tumor cells, only fibrotic mass (total regression or response)

Secondary outcome measures

1. Safety: measured with National Cancer Institute Common Terminology Criteria (NCI-CTC) scale, version 3.0
2. Relapse-free survival : the time from the date of starting CRT to the date on which either of recurrence, progression, or death was first observed, or the date of last follow-up
3. Overall survival: the time from the date of starting CRT to the date of death from any cause or last follow-up
4. Pharmacogenetic analysis: genomic DNA from peripheral blood will be analyzed for the following polymorphism: CYP2A6*4 (whole deletion of CYP2A6), CYP2A6*7 (6558T>G, rs5031016), CYP2A6*9 (-48T>G, rs28399433), CYP2A6*10 (6558T>C and 6600G>T, rs28399468), UMPS 638G>C (rs1801019), ABCB1 3545 C>T (rs1045642), ABCB1 1236 C>T (rs1128503), and ABCB1 2677 G>T/A (rs2032582)

Overall trial start date

20/10/2008

Overall trial end date

30/11/2012

Reason abandoned

Eligibility

Participant inclusion criteria

1. Histologically diagnosed adenocarcinoma of rectum
2. Located within 8cm from anal verge
3. cT3/4 by rectal MRI+/- endorectal ultrasound
4. 18 years old or more
5. ECOG performance status <=2
6. No previous chemotherapy
7. No previous radiotherapy to pelvis
8. Adequate bone marrow, hepatic, and renal function

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

121

Participant exclusion criteria

1. Rectal cancer of histology other than adenocarcinoma
2. Adenocarcinoma developed from inflammatory bowel disease
3. Presence of distant metastases
4. Existence of unresected synchronous colon cancer
5. Unresolved bowel obstruction
6. Clinically unresectable disease
7. Uncontrolled cardiovascular disease
8. Uncontrolled active infection
9. History of other malignancies within 5 years from screening
10. History of organ transplantation that necessitates immunosuppressive treatment
11. Uncontrolled epileptic disease or psychiatric disease
12. Pregnant or breastfeeding women, or women with child-bearing potential who are not compliant to 13. Contraception policy of this study

Recruitment start date

09/01/2009

Recruitment end date

28/08/2012

Locations

Countries of recruitment

Korea, South

Trial participating centre

National Cancer Center
323 Ilsan=ro, Ilsandong-gu
Goyang
10408
Korea, South

Sponsor information

Organisation

National Cancer Center

Sponsor details

323 Ilsan-ro
Ilsandong-gu
Goyang
10408
Korea
South

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Not defined

Funder name

National Cancer Center

Alternative name(s)

NCC

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Korea, South

Results and Publications

Publication and dissemination plan

Intention to publish date

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes