Preoperative Sequential Short-course Radiation Therapy and FOLFOX for Locally Advanced Rectal Cancer
- Conditions
- Rectal Cancer
- Interventions
- Radiation: short-course radiotherapyRadiation: ChemoradiotherapyDrug: mFOLFOX6Procedure: TME surgery
- Registration Number
- NCT05673772
- Lead Sponsor
- Kyungpook National University Hospital
- Brief Summary
The treatment protocol proposed in this study is to perform short-term radiation therapy and 4 cycles of FOLFOX chemotherapy for neoadjuvant treatment of locally advanced rectal cancer. Compared to conventional chemoradiation therapy, the preoperative radiotherapy period is shortened, and the cure rate of rectal cancer patients can be improved by early treatment of micrometastasis using systemic chemotherapy. The patients who are assigned to the study group will received the short-course radiotherapy and 4 cycles of FOLFOX and patients in the control will received conventional chemoradiotherapy for preoperative treatment. All patients are recommended to receive total mesorectal excision (TME) after neoadjuvant treatment and adjuvant chemotherapy will be given according to the pathological stage.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 364
- Asian
- ECOG (Eastern Cooperative Oncology Group) performance status 0-2
- Pathologically confirmed rectal cancer (rectal cancer located 10 cm or low from the anal verge in pelvis MRI)
- Histologic type: adenocarcinoma, mucinous carcinoma, and signet ring cell carcinoma
- Locally advanced rectal cancer with one or more of the following factors based on pelvis MRI: cTanyN1-2, cT3-4N0, or presence of extramural vascular invasion
- MRI findings such as pelvic lymph node metastasis, anal sphincter invasion, and T4b are not included in the exclusion criteria, which cases will be enrolled by the researcher's discretion
- Patients with appropriate organ (bone marrow, kidney, liver) function
- A person who understands the study and willing to provide informed consent
(one of the following criteria)
- Colon cancer or rectal cancer located more than 10 cm from the anal verge
- Stage I rectal cancer (clinical stage cT1-2N0)
- Clinically or pathologically diagnosed distant metastasis (cTanyNanyM1)
- Familial adenomatous polyposis
- Hereditary nonpolyposis colorectal cancer
- History of chemotherapy or radiotherapy within 6 months
- History of colorectal cancer or other type of malignancy within 5 years (except for cured nonmelanoma skin or in situ cervical cancer)
- Comorbidities that make it difficult to undergo chemotherapy or radiotherapy
- Bone marrow suppression with neutrophil count <2 ×109/L or platelet count <100 ×109/L prior to the first chemotherapy
- Peripheral sensory neuropathy with functional impairment (grade 2 or higher)
- Severe renal dysfunction (GFR ≤30ml/min by Wright or Cockroft formula)
- Severe hepatic dysfunction
- Genetic problems such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
- Taking tegafur, gimeracil, and oteracil potassium complex and those within 7 days of discontinuation
- Taking sorivudine or brivudine
- Significant heart disease or myocardial infarction within the last 6 months
- Hereditary diseases or history of coagulopathy
- Central nervous system disorders with disability or mental disorders
- Pregnant or lactating women
- Currently participating in other clinical trials or receiving research medication
- Unhealed wounds, fractures, peptic ulcer, abscesses in the abdominal cavity
- Active gastrointestinal bleeding
- Active infections requiring antibiotics for injection
- Emergency Surgery
- History of hypersensitivity to the drugs in study protocol
- Patients with non-malignant tumor diseases
- Dihydropyrimidine dehydrogenase deficiency
- Not willing to participate
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Study group mFOLFOX6 Short-course radiotherapy and 4 cycles of mFOLFOX6 followed by TME. Adjuvant chemotherapy will be given according to the pathological stage (CR\~pStageI: 6 cycles of capecitabine or 4 cycles of 5-FU with leucovorin, pStageII-III: 8 cycles of mFOLFOX6) Study group short-course radiotherapy Short-course radiotherapy and 4 cycles of mFOLFOX6 followed by TME. Adjuvant chemotherapy will be given according to the pathological stage (CR\~pStageI: 6 cycles of capecitabine or 4 cycles of 5-FU with leucovorin, pStageII-III: 8 cycles of mFOLFOX6) Control group TME surgery Conventional chemoradiotherapy followed by TME. Adjuvant chemotherapy will be given according to the pathological stage (CR\~pStageI: 6 cycles of capecitabine or 4 cycles of 5-FU with leucovorin, pStageII-III: 8 cycles of mFOLFOX6) Study group TME surgery Short-course radiotherapy and 4 cycles of mFOLFOX6 followed by TME. Adjuvant chemotherapy will be given according to the pathological stage (CR\~pStageI: 6 cycles of capecitabine or 4 cycles of 5-FU with leucovorin, pStageII-III: 8 cycles of mFOLFOX6) Control group Chemoradiotherapy Conventional chemoradiotherapy followed by TME. Adjuvant chemotherapy will be given according to the pathological stage (CR\~pStageI: 6 cycles of capecitabine or 4 cycles of 5-FU with leucovorin, pStageII-III: 8 cycles of mFOLFOX6)
- Primary Outcome Measures
Name Time Method 5-year disease-free survival 3 years To compare the 3-year disease-free survival between the experimental arm and the control arm
- Secondary Outcome Measures
Name Time Method R0 resection within 30 days after TME Rate of R0 resection of TME
Incidence of peripheral neuropathy 3 years Incidence of oxaliplatin-induced peripheral neuopathy
Loco-regional recurrence 5 years To compare the 3 year and 5-year loco-regional recurrence between the experimental arm and the control arm
pCR rate within 30 days after TME CR (complete regression), no tumor cells and only fibrotic mass or acellular mucin pools
Toxicity of neoadjuvant radiotherapy and chemotherapy 6 months Neoadjuvant treatment associated toxicity (Common Terminology Criteria for Adverse Events version v5.0)
Surgical complications within 60 days after TME Surgical complications classified according to the Clavien-Dindo classification
European Organization for Research and Treatment of Cancer Quality of Life CR29 2 year after surgery The QLQ-CR29 has five functional and 18 symptom scales. It contains four subscales (urinary frequency (UF), blood and mucus in stool (BMS), stool frequency (SF), and body image (BI)) and 19 single items (urinary incontinence, dysuria, abdominal pain, buttock pain, bloating, dry mouth, hair loss, taste, anxiety, weight, flatulence, fecal incontinence, sore skin, embarrassment, stoma care problems, sexual interest (men), impotence, sexual interest (women), and dyspareunia) \[11\]. Patients are asked to indicate their symptoms during the past week(s). Scores can be linearly transformed to provide a score from 0 to 100. Higher scores represent better functioning on the functional scales and a higher level of symptoms on the symptom scales.
5-year overall survival 5 years To compare the 5-year overall survival between the experimental arm and the control arm
Distant metastasis 5 years To compare the 3 year and 5-year distant metastasis between the experimental arm and the control arm
European Organization for Research and Treatment of Cancer Quality of Life C30 2 year after surgery The EORTC Core Questionnaire (QLQ-C30) includes six clearly distinguishable functioning scales that have been thoroughly tested and validated on an international level and that are available in 110 different language versions
The International Index of Erectile Function-5 score, retrograde ejaculation 2 year after surgery Quality of life IIEF-5, retrograde ejaculation
3-year overall survival 3 years To compare the 3-year overall survival between the experimental arm and the control arm
TRG within 30 days after TME Pathological tumor regression grade (TRG) (Dworak/Mandard/AJCC TRG classification)
Low Anterior Resection Syndrome score 2 year after surgery Low anterior resection syndrome (LARS) score ; 0 to 20 (no LARS), 21 to 29 (minor LARS ) and 30 to 42 (Major LARS )
5-year disease-free survival 5 years To compare the 5-year disease-free survival between the experimental arm and the control arm
Trial Locations
- Locations (9)
Chungnam National University Hospital
🇰🇷Daejeon, Korea, Republic of
Jeonbuk National University Hospital
🇰🇷Jeonju, Korea, Republic of
Gyu seog Choi
🇰🇷Daegu, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Gwangju, Korea, Republic of
Catholic University of Korea Incheon St. Mary's Hospital
🇰🇷Incheon, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Gangnam Severance Hospital
🇰🇷Seoul, Korea, Republic of
, Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seoul, Korea, Republic of