Clinical trial NCT05673772: Preoperative Sequential Short-course Radiation Therapy and FOLFOX for Locally Advanced Rectal Cancer
Official title: A Multicenter, Randomized Controlled Trial of Preoperative Sequential Short-course Radiation Therapy and Oxaliplatin-based Consolidation Chemotherapy for Locally Advanced Rectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: Rectal cancer
Neoadjuvant treatment
short-course radiotherapy
Consolidation chemotherapy
Lead sponsor: Kyungpook National University Hospital
Sponsor class: OTHER
Collaborators: name: National Cancer Center, Korea
First posted: 2023-01-06
Enrollment: 364
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria: (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

Primary outcomes:
measure: 5-year disease-free survival
timeFrame: 3 years
Secondary outcomes:
measure: pCR rate
timeFrame: within 30 days after TME
measure: Toxicity of neoadjuvant radiotherapy and chemotherapy
timeFrame: 6 months
measure: R0 resection
timeFrame: within 30 days after TME
measure: TRG
timeFrame: within 30 days after TME
measure: Surgical complications
timeFrame: within 60 days after TME
measure: Incidence of peripheral neuropathy
timeFrame: 3 years
measure: European Organization for Research and Treatment of Cancer Quality of Life C30
timeFrame: 2 year after surgery
measure: European Organization for Research and Treatment of Cancer Quality of Life CR29
timeFrame: 2 year after surgery
measure: Low Anterior Resection Syndrome score
timeFrame: 2 year after surgery
measure: The International Index of Erectile Function-5 score, retrograde ejaculation
timeFrame: 2 year after surgery
measure: 5-year disease-free survival
timeFrame: 5 years
measure: 3-year overall survival
timeFrame: 3 years
measure: 5-year overall survival
timeFrame: 5 years
measure: Loco-regional recurrence
timeFrame: 5 years
measure: Distant metastasis
timeFrame: 5 years
Other outcomes:
Locations:
city: Daegu
country: Korea, Republic of
facility: Gyu seog Choi
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Incheon
country: Korea, Republic of
facility: Catholic University of Korea Incheon St. Mary's Hospital
city: Jeonju
country: Korea, Republic of
facility: Jeonbuk National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: , Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
Study officials:
References: