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

Rectal Cancer Clinical Trial

— SOLAR  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05673772
• Other study ID #: KNUHCRC007
• Status: Recruiting
• Phase: Phase 2
• Start date: October 23, 2020
• Est. completion date: December 31, 2029

Study information

• Verified date: July 2023
• Source: Kyungpook National University Hospital
• Contact: Soo Yeun Park, M.D.
• Phone: +82-53-200-3867
• Email: psy-flower[@]daum.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 364
• Est. completion date: December 31, 2029
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

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

Radiation:
• Chemoradiotherapy
45~50.4 Gy/25fr with concurrent use of either capecitabine or 5-FU+leucovorin(or levoleucovorin or leucosodium)

Procedure:
• TME surgery
TME surgery

Locations

Country	Name	City	State
Korea, Republic of	Gyu seog Choi	Daegu
Korea, Republic of	Chungnam National University Hospital	Daejeon
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	Jeonbuk National University Hospital	Jeonju
Korea, Republic of	, Korea University Anam Hospital	Seoul
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Seoul National University Bundang Hospital	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Kyungpook National University Hospital	National Cancer Center, Korea

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

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