Overview

This trial is active, not recruiting.

Conditions rectal neoplasms, adenocarcinoma
Treatments capecitabine oxaliplatin, pelvic radiation capecitabine 5-fluorouracil
Phase phase 2
Sponsor National Cancer Center, Korea
Collaborator Korean Cancer Study Group
Start date June 2014
End date December 2016
Trial size 110 participants
Trial identifier NCT01952951, KCSG CO14-03

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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)
capecitabine oxaliplatin Xeloda
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.
pelvic radiation capecitabine 5-fluorouracil preoperative chemoradiation
50.4Gy of pelvic radiation with capecitabine or 5-fluorouracil
(Active Comparator)
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)
pelvic radiation capecitabine 5-fluorouracil preoperative chemoradiation
50.4Gy of pelvic radiation with capecitabine or 5-fluorouracil

Primary Outcomes

Measure
downstaging rate
time frame: expected average of 15 weeks after start of study treatment

Secondary Outcomes

Measure
pathologic response
time frame: 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
toxicity profile
time frame: expected average of 35 weeks after start of study treatment
pattern of failure
time frame: 3 years after surgery
local control rate
time frame: 3 years after surgery
relapse-free survival
time frame: 3 years after surgery
Disease-free survival
time frame: 3 years after surgery
overall survival
time frame: 3 years after surgery
quality of life
time frame: before study treatment, 7 weeks after completion of chemoradiation, and at 4 weeks after surgery

Eligibility Criteria

Male or female participants at least 20 years old.

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

Additional Information

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)
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.
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by National Cancer Center, Korea.