SOLAR: Preoperative Sequential Short-course Radiation Therapy and FOLFOX for Locally Advanced Rectal Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| 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) |
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
|
Outcome Measures
Primary Outcome Measures
- Disease-free survival [3 years]
To compare the 3-year disease-free survival between the experimental arm and the control arm
Secondary Outcome Measures
- 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)
- R0 resection [within 30 days after TME]
Rate of R0 resection of TME
- TRG [within 30 days after TME]
Pathological tumor regression grade (TRG) (Dworak/Mandard/AJCC TRG classification)
- Surgical complications [within 60 days after TME]
Surgical complications classified according to the Clavien-Dindo classification
- Incidence of peripheral neuropathy [3 years]
Incidence of oxaliplatin-induced peripheral neuopathy
- 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
- 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.
- 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 )
- The International Index of Erectile Function-5 score, retrograde ejaculation [2 year after surgery]
Quality of life IIEF-5, retrograde ejaculation
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Asian
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ECOG (Eastern Cooperative Oncology Group) performance status 0-2
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Histologically proven rectal cancer (the lowest border of the tumor located ≤ 10 cm from the anal verge)
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Histological type: adenocarcinoma, mucinous carcinoma, or signet ring cell carcinoma
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at least one of the following criteria on pelvic MRI (cTanyN1-2, cT3-4N0, TanymrEMVI (+))
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MRI scan findings such as pelvic lymph node metastases, sphincter i involvement, (mesorectal fascia) (MRF) (+), and T4b are not exclusion criteria, and are at the discretion of the researcher.
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Adequate hematologic/renal/hepatic function WBC > 3.0×109/L, Platelet>100×109/L / direct bilirubin<0.4mg/dl / GFR>50ml/min by Wright or Cockroft formula /
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Patients who listen to and understand the explanation of the study and sign the consent form
Exclusion Criteria: (one of the following criteria)
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Colon cancer or rectal cancer located at above the anal verge 10 cm
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cT1-2N0 on pelvis MRI (magnetic Resonance Imaging)
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Distant metastasis
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Familial Adenomatous polyposis
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Hereditary non-polyposis colorectal cancer
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Systemic chemotherapy or radiotherapy within 6 months
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History of colorectal cancer
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or other type of malignancy within 5 years (Exceptions are made for cured non-melanoma skin cancer or in situ neck cancer.)
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Patients who are is judged that it is difficult to receive chemotherapy or radiotherapy due to an underlying disease or systemic condition
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Patients with bone marrow suppression with neutrophil count < 2 x 109/L and/or platelet count < 100 x 109/L prior to the first chemotherapy administration cycle
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Patients with peripheral sensory neuropathy with functional impairment prior to the first administration cycle (grade 2 or higher) (peripheral nerve symptoms may worsen)
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Severe renal dysfunction (GFR ≤30ml/min by Wright or Cockroft formula)
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Severe hepatic dysfunction
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Patients with genetic problems such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
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Patients receiving Tegafur, Gimeracil, and Oteracil potassium combination drugs and those within 7 days of discontinuation
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Patients receiving sorivudine or brivudine
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Patients with a history of another malignant disease within the last 5 years
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Patients with clinically significant heart disease or myocardial infarction within the past 6 months
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A history of hereditary diseases or hemocoagulopathy that pose a risk of bleeding
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Patients with central nervous system disorders or a history of mental disorders and patients with evidence of central nervous system metastases
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Pregnant or lactating women
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Patients currently participating in other clinical trials or receiving investigational drugs
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Unhealed wounds, fractures, peptic ulcer, abscesses in the abdominal cavity
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Active gastrointestinal bleeding
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Active infections requiring antibiotics for injection
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Emergency Surgery
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Patients with a history of hypersensitivity reactions to the components of the investigational drug
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Patients with non-malignant tumor diseases
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Patients known to have dihydropyrimidine dehydrogenase deficiency
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Patients who do not wish to participate in this study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Gyu seog Choi | Daegu | Korea, Republic of | 702-210 | |
| 2 | Chungnam National University Hospital | Daejeon | Korea, Republic of | ||
| 3 | Chonnam National University Hwasun Hospital | Gwangju | Korea, Republic of | ||
| 4 | Catholic University of Korea Incheon St. Mary's Hospital | Incheon | Korea, Republic of | ||
| 5 | Jeonbuk National University Hospital | Jeonju | Korea, Republic of | ||
| 6 | Asan Medical Center | Seoul | Korea, Republic of | 05505 | |
| 7 | , Korea University Anam Hospital | Seoul | Korea, Republic of | ||
| 8 | Gangnam Severance Hospital | Seoul | Korea, Republic of | ||
| 9 | Seoul National University Bundang Hospital | Seoul | Korea, Republic of |
Sponsors and Collaborators
- Kyungpook National University Hospital
- National Cancer Center, Korea
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- KNUHCRC007