TNT to Increase the Clinical Complete Response Rate for Distal LARC

Phase 2

Active, not recruiting

• Conditions: Rectal Cancer; Rectal Cancer Stage II; Rectal Cancer Stage III; Chemoradiation
• Interventions: Drug: Capecitabine, Oxaliplatin; Radiation: External beam radiotherapy; Procedure: Surgery; Other: Watch and wait strategy

• Registration Number: NCT03840239
• Lead Sponsor: Sun Yat-sen University

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.

Study Timeline

• Study Start: 2018-12-25
• Study First Submitted: 2019-01-28
• Study First Submitted QC: 2019-02-12
• Study First Posted: 2019-02-15
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-24
• Last Update Posted: 2023-10-25
• Primary Completion: 2023-12-30
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 98

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TNT arm	Surgery	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.
TNT arm	External beam radiotherapy	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.
TNT arm	Watch and wait strategy	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.
TNT arm	Capecitabine, Oxaliplatin	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.

Primary Outcome Measures

Name	Time	Method
Rate of clinical complete response	1.5 year after diagnosis	Rate of clinical complete response

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China