TNT to Increase the Clinical Complete Response Rate for Distal LARC (TESS)

Sun Yat-sen University

Status and phase: Active, not recruiting; Phase 2

Conditions: Chemoradiation; Rectal Cancer Stage III; Rectal Cancer Stage II; Rectal Cancer

Treatments: Drug: Capecitabine, Oxaliplatin; Radiation: External beam radiotherapy; Other: Watch and wait strategy; Procedure: Surgery

Study type: Interventional

Funder types: Other

Identifiers

NCT03840239

2018-FXY-149

5010-2018-04 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 98 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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98 participants in 1 patient group

TNT arm

Experimental group

Description:

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.

Treatment:

Radiation: External beam radiotherapy

Drug: Capecitabine, Oxaliplatin

Other: Watch and wait strategy

Procedure: Surgery