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

A Multicenter, Randomized Controlled Trial of Preoperative Sequential Short-course Radiation Therapy and Oxaliplatin-based Consolidation Chemotherapy for Locally Advanced Rectal Cancer

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 Overview

• Status: Active, not recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Radiation: short-course radiotherapy; Drug: mFOLFOX6; Procedure: TME surgery; Radiation: Chemoradiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 364
• Phase: Phase 2

Contacts and Locations

Study Locations

• South Korea
  • Daegu, South Korea, 702-210
    • Gyu seog Choi
  • Daejeon, South Korea
    • Chungnam National University Hospital
  • Gwangju, South Korea
    • Chonnam National University Hwasun Hospital
  • Incheon, South Korea
    • Catholic university of Korea Incheon St. Mary's Hospital
  • Jeonju, South Korea
    • Jeonbuk National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea
    • Gangnam Severance Hospital
  • Seoul, South Korea
    • Seoul National University Bundang Hospital
  • Seoul, South Korea
    • , Korea University Anam Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study group; 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)	Radiation: short-course radiotherapy; 25 Gy in 5 fractions for 5 days; Drug: mFOLFOX6; Oxaliplatin 85 mg/m2, Levoleucovorin 200mg (or Leucovroin, Leucosodium 400mg)/m2, 5- FU 400 mg/m2, and continuous 5- FU 2,400 mg/m2 for 46 hours; Procedure: TME surgery; TME surgery
Active Comparator: Control group; 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)	Procedure: TME surgery; TME surgery; Radiation: Chemoradiotherapy; 45~50.4 Gy/25fr with concurrent use of either capecitabine or 5-FU+leucovorin(or levoleucovorin or leucosodium)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year disease-free survival	To compare the 3-year disease-free survival between the experimental arm and the control arm	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR rate	CR (complete regression), no tumor cells and only fibrotic mass or acellular mucin pools	within 30 days after TME
Toxicity of neoadjuvant radiotherapy and chemotherapy	Neoadjuvant treatment associated toxicity (Common Terminology Criteria for Adverse Events version v5.0)	6 months
R0 resection	Rate of R0 resection of TME	within 30 days after TME
TRG	Pathological tumor regression grade (TRG) (Dworak/Mandard/AJCC TRG classification)	within 30 days after TME
Surgical complications	Surgical complications classified according to the Clavien-Dindo classification	within 60 days after TME
Incidence of peripheral neuropathy	Incidence of oxaliplatin-induced peripheral neuopathy	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	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.	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 )	2 year after surgery
The International Index of Erectile Function-5 score, retrograde ejaculation	Quality of life IIEF-5, retrograde ejaculation	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	5 years
3-year overall survival	To compare the 3-year overall survival between the experimental arm and the control arm	3 years
5-year overall survival	To compare the 5-year overall survival between the experimental arm and the control arm	5 years
Loco-regional recurrence	To compare the 3 year and 5-year loco-regional recurrence between the experimental arm and the control arm	5 years
Distant metastasis	To compare the 3 year and 5-year distant metastasis between the experimental arm and the control arm	5 years

Collaborators and Investigators

• Sponsor: Kyungpook National University Hospital
• Collaborators: National Cancer Center, Korea

Publications and helpful links

General Publications

• Kang MK, Park SY, Park JS, Kim HJ, Kim JG, Kang BW, Baek JH, Cho SH, Seo AN, Kim DW, Kim J, Baek SJ, Kim JH, Kim JY, Ha GW, Park EJ, Park IJ, Kim CH, Kang H, Choi GS. Preoperative sequential short-course radiation therapy and FOLFOX chemotherapy versus long-course chemoradiotherapy for locally advanced rectal cancer: a multicenter, randomized controlled trial (SOLAR trial). BMC Cancer. 2023 Nov 3;23(1):1059. doi: 10.1186/s12885-023-11363-7.

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2020
• Primary Completion (Estimated): December 28, 2028
• Study Completion (Estimated): December 28, 2031

Study Registration Dates

• First Submitted: December 21, 2022
• First Submitted That Met QC Criteria: December 21, 2022
• First Posted (Actual): January 6, 2023

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Consolidation chemotherapy; Rectal cancer; Neoadjuvant treatment; short-course radiotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms; Therapeutics; Drug Therapy; Radiotherapy; Combined Modality Therapy; Chemoradiotherapy
• Other Study ID Numbers: KNUHCRC007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No