Clinical trial NCT03840239: TNT to Increase the Clinical Complete Response Rate for Distal LARC
Official title: Total Neoadjuvant trEatment to Increase the Clinical Complete reSponse Rate for diStal Locally Advanced Rectal Cancer (TESS)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Rectal Cancer
Rectal Cancer Stage II
Rectal Cancer Stage III
Chemoradiation
Keywords: rectal cancer
chemoradiation
total neoadjuvant treatment
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2019-02-15
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of clinical complete response
timeFrame: 1.5 year after diagnosis
Secondary outcomes:
measure: Ratio of sphincter preservation strategy
timeFrame: 1.5 year after diagnosis
measure: Rate of pathological complete response and tumor regression grade distribution
timeFrame: 1.5 year after diagnosis
measure: Acute toxicity
timeFrame: Within the first course of anti-tumor treatment
measure: Rate of surgical complications
timeFrame: 1.5 year after diagnosis
measure: Long-term anal function
timeFrame: 1.5 year after diagnosis
measure: Long-term toxicity grading
timeFrame: 3 year after the end of the first course of anti-tumor treatment
measure: ECOG standard score
timeFrame: 1.5 year after diagnosis
measure: 3 year disease free survival
timeFrame: 3 year after the end of the first course of anti-tumor treatment
measure: 5 year overall survival
timeFrame: 5 year after the end of the first course of anti-tumor treatment
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: WeiWei Xiao
role: PRINCIPAL_INVESTIGATOR
References: