Clinical trial NCT01952951: Preoperative Chemoradiation Followed by Chemotherapy for Locally Advanced Rectal Cancer
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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Rectal Neoplasms
Adenocarcinoma
Keywords: rectal neoplasms
radiotherapy
Antineoplastic Agents
Lead sponsor: National Cancer Center, Korea
Sponsor class: OTHER_GOV
Collaborators: name: Korean Cancer Study Group
First posted: 2013-09-30
Enrollment: 110
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: downstaging rate
timeFrame: expected average of 15 weeks after start of study treatment
Secondary outcomes:
measure: pathologic response
timeFrame: expected average of 15 weeks after start of study treatment
measure: radiologic response rate
timeFrame: expected average of 14 weeks after start of study treatment
measure: toxicity profile
timeFrame: expected average of 35 weeks after start of study treatment
measure: pattern of failure
timeFrame: 3 years after surgery
measure: local control rate
timeFrame: 3 years after surgery
measure: relapse-free survival
timeFrame: 3 years after surgery
measure: Disease-free survival
timeFrame: 3 years after surgery
measure: overall survival
timeFrame: 3 years after surgery
measure: quality of life
timeFrame: before study treatment, 7 weeks after completion of chemoradiation, and at 4 weeks after surgery
Other outcomes:
Locations:
city: Goyang
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Anyang
country: Korea, Republic of
facility: Hallym University Sacred Heart Hospital
city: Gangneung
country: Korea, Republic of
facility: Gangneung Asan Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Chung-Ang University Hospital
Study officials:
affiliation: Asan Medical Center
name: Sun Young Kim, MD
role: STUDY_CHAIR
References:
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.