Chemoradiation, Rectal Cancer, Rectal Cancer Stage II, Rectal Cancer Stage III
Conditions
Keywords
rectal cancer, chemoradiation, total neoadjuvant treatment
Brief summary
This is a open-label, single-arm study to investigate the safety and efficacy of total neoadjuvant treatment (TNT) in patients with locally advanced resectable rectal cancer.
Detailed description
Standard treatment of rectal cancer is neoadjuvant capecitabine chemotherapy with radiotherapy, followed by total mesorectal excision. A new concept suggests organ preservation as an alternative to rectal excision in good responders after neoadjuvant radiochemotherapy to decrease surgical morbidity and increase quality of life. The rational is the fact that 15%-20% of patients have sterilized tumours after chemoradiotherpay for locally advanced rectal cancer. As compared to capecitabine alone, oxaliplatin and more intensified chemotherapy have been shown to increase tumor regression in the neoadjuvant chemoradiation setting. Meanwhile, prolong of time interval from the end of radiotherapy to assessment of tumor response could further increase pathologic complete response rate and complete clinical response rate. The objective of this trial is to increase the rate of clinical complete response for distal rectal cancer patients by optimizing tumour response. The investigators expect to increase chance of clinical complete response by using total neoadjuvant treatment regimen as compared to conventional chemoradiotherapy alone.
Interventions
Drug: Capecitabine, Oxaliplatin
RADIATIONExternal beam radiotherapy
External beam radiotherapy to the primary tumor, regional lymph nodes and clinical target volume
PROCEDURESurgery
'Local excision' or 'Intersphincter resection' or 'Total mesorectal excision' or other surgeries
Watch and wait strategy recommendation and discussion for cCR patients
Sponsors
Sun Yat-sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Rectal adenocarcinoma * cT3-4aNany or cTanyN+ * Location ≤5 cm from the anal verge * No distant metastasis * No gastrointestinal obstruction or relieved obstruction * No previous surgery of the rectum, no previous chemotherapy, no previous pelvic radiation, no previous biotherapy * ECOG 0-1 * Expected survival length ≥ 2 years * Age 18-70 * Sufficient bone marrow, kidney and liver function * Effective contraception during the study * Patient and doctor have signed informed consent
Exclusion criteria
* Distant metastasis * Chronic intestinal inflammation and/or bowel obstruction * Contra indication for chemotherapy and/or radiotherapy * Previous pelvic radiotherapy or chemotherapy * Severe renal, hepatic insufficiency (serum creatinine\<30ml/min) * Peripheral neuropathy \> grade 1 * Pregnant or breast-feeding woman * Certain or suspicious allergy to research drug * Cachexia, organ dysfunction * Active severe infection * Multiple primary cancers * Epileptic seizures * Malignant history within 5 years, except cervical carcinoma in situ or cutaneous basal cell carcinoma * Severe arrhythmia, cardiac dysfunction (NYHA grade III or IV ) * Uncontollable severe hypertesion * Persons deprived of liberty or under guardianship * Impossibility for compliance to follow-up
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of clinical complete response | 1.5 year after diagnosis | Rate of clinical complete response |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of pathological complete response and tumor regression grade distribution | 1.5 year after diagnosis | Rate of pathological complete response and tumor regression grade distribution |
| Acute toxicity | Within the first course of anti-tumor treatment | Acute toxicity according to CTCAE 5.0 |
| Rate of surgical complications | 1.5 year after diagnosis | Rate of surgical complications |
| Long-term anal function | 1.5 year after diagnosis | Long-term anal function according to Wexner Continence Grading Scale |
| Ratio of sphincter preservation strategy | 1.5 year after diagnosis | Number of patients with sphincter preservation through Watch and wait strategy, or local excision, or intersphincter resection, or low anterior resection, etc. |
| ECOG standard score | 1.5 year after diagnosis | ECOG standard score |
| 3 year disease free survival | 3 year after the end of the first course of anti-tumor treatment | 3 year disease free survival |
| 5 year overall survival | 5 year after the end of the first course of anti-tumor treatment | 5 year overall survival |
| Long-term toxicity grading | 3 year after the end of the first course of anti-tumor treatment | Long-term toxicity grading according to CTCAE 5.0 |
Countries
China
Outcome results
None listed