Preoperative Sequential Short-course Radiation Therapy and FOLFOX for Locally Advanced Rectal Cancer

Phase 2Active Not RecruitingNCT05673772

Kyungpook National University Hospital364 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

364

Conditions

Rectal Cancer

Interventions

Eligibility

Sex: ALLMin age: 20 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (9)

Gyu seog Choi

Daegu, South Korea

Chungnam National University Hospital

Daejeon, South Korea

Chonnam National University Hwasun Hospital

Gwangju, South Korea

Catholic University of Korea Incheon St. Mary's Hospital

Incheon, South Korea

Jeonbuk National University Hospital

Jeonju, South Korea

Asan Medical Center

Seoul, South Korea

, Korea University Anam Hospital

Seoul, South Korea

Gangnam Severance Hospital

Seoul, South Korea

Seoul National University Bundang Hospital

Seoul, South Korea

Outcomes

Primary Outcomes

3-year disease-free survival

To compare the 3-year disease-free survival between the experimental arm and the control arm

Time frame: 3 years

Secondary Outcomes

pCR rate

CR (complete regression), no tumor cells and only fibrotic mass or acellular mucin pools

Time frame: within 30 days after TME

Toxicity of neoadjuvant radiotherapy and chemotherapy

Neoadjuvant treatment associated toxicity (Common Terminology Criteria for Adverse Events version v5.0)

Time frame: 6 months

R0 resection

Rate of R0 resection of TME

Time frame: within 30 days after TME

TRG

Pathological tumor regression grade (TRG) (Dworak/Mandard/AJCC TRG classification)

Time frame: within 30 days after TME

Surgical complications

Surgical complications classified according to the Clavien-Dindo classification

Time frame: within 60 days after TME

Incidence of peripheral neuropathy

Incidence of oxaliplatin-induced peripheral neuopathy

Time frame: 3 years

European Organization for Research and Treatment of Cancer Quality of Life C30

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

Time frame: 2 year after surgery

European Organization for Research and Treatment of Cancer Quality of Life CR29

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.

Time frame: 2 year after surgery

Low Anterior Resection Syndrome score

Low anterior resection syndrome (LARS) score ; 0 to 20 (no LARS), 21 to 29 (minor LARS ) and 30 to 42 (Major LARS )

Time frame: 2 year after surgery

The International Index of Erectile Function-5 score, retrograde ejaculation

Quality of life IIEF-5, retrograde ejaculation

Time frame: 2 year after surgery

5-year disease-free survival

To compare the 5-year disease-free survival between the experimental arm and the control arm

Time frame: 5 years

3-year overall survival

To compare the 3-year overall survival between the experimental arm and the control arm

Time frame: 3 years

5-year overall survival

To compare the 5-year overall survival between the experimental arm and the control arm

Time frame: 5 years

Loco-regional recurrence

To compare the 3 year and 5-year loco-regional recurrence between the experimental arm and the control arm

Time frame: 5 years

Distant metastasis

To compare the 3 year and 5-year distant metastasis between the experimental arm and the control arm

Time frame: 5 years