TESS: TNT Versus Conventional CRT to Increase the Sphincter Preservation for Distal LARC
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: TNT arm Drug: Neoadjuvant chemotherapy Capeox (Capecitabine + Oxaliplatin), 6 cycles; adjuvant chemotherapy, Capecitabine, 2 cycles or physicians' decision. External beam radiotherapy: Neoadjuvant, 50 Gy, 2 Gy/session; 25 fractions. Procedure: 'Watch and wait strategy' or surgery including local excision, intersphincter resection or total mesorectal excision or other kinds of surgeries. |
Drug: Capecitabine, Oxaliplatin
Drug: Capecitabine, Oxaliplatin
Radiation: External beam radiotherapy
External beam radiotherapy to the primary tumor, regional lymph nodes and clinical target volume
Procedure: Surgery
'Local excision' or 'Intersphincter resection' or 'Total mesorectal excision' or other surgeries
Other: Watch and wait strategy
Watch and wait strategy recommendation and discussion for cCR patients
|
Outcome Measures
Primary Outcome Measures
- Rate of clinical complete response [1.5 year after diagnosis]
Rate of clinical complete response
Secondary Outcome Measures
- 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.
- 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
- 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
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Rectal adenocarcinoma
-
cT3-4aNany or cTanyN+
-
Location ≤5 cm from the anal verge
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No distant metastasis
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No gastrointestinal obstruction or relieved obstruction
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No previous surgery of the rectum, no previous chemotherapy, no previous pelvic radiation, no previous biotherapy
-
ECOG 0-1
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Expected survival length ≥ 2 years
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Age 18-70
-
Sufficient bone marrow, kidney and liver function
-
Effective contraception during the study
-
Patient and doctor have signed informed consent
Exclusion Criteria:
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Distant metastasis
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Chronic intestinal inflammation and/or bowel obstruction
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Contra indication for chemotherapy and/or radiotherapy
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Previous pelvic radiotherapy or chemotherapy
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Severe renal, hepatic insufficiency (serum creatinine<30ml/min)
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Peripheral neuropathy > grade 1
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Pregnant or breast-feeding woman
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Certain or suspicious allergy to research drug
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Cachexia, organ dysfunction
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Active severe infection
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Multiple primary cancers
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Epileptic seizures
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Malignant history within 5 years, except cervical carcinoma in situ or cutaneous basal cell carcinoma
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Severe arrhythmia, cardiac dysfunction (NYHA grade III or IV )
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Uncontollable severe hypertesion
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Persons deprived of liberty or under guardianship
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Impossibility for compliance to follow-up
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sun Yat-sen University Cancer Center | Guangzhou | Guangdong | China | 510060 |
Sponsors and Collaborators
- Sun Yat-sen University
Investigators
- Principal Investigator: WeiWei Xiao, Sun Yat-sen University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2018-FXY-149
- 5010-2018-04