TNT to Increase the Clinical Complete Response Rate for Distal LARC

NCT ID: NCT03840239

Last Updated: 2023-10-25

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-25
• Study Completion Date: 2027-06-30

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.

Conditions

Rectal Cancer; Rectal Cancer Stage II; Rectal Cancer Stage III; Chemoradiation

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Capecitabine, Oxaliplatin

Intervention Type: DRUG

Drug: Capecitabine, Oxaliplatin

External beam radiotherapy

Intervention Type: RADIATION

External beam radiotherapy to the primary tumor, regional lymph nodes and clinical target volume

Surgery

Intervention Type: PROCEDURE

'Local excision' or 'Intersphincter resection' or 'Total mesorectal excision' or other surgeries

Watch and wait strategy

Intervention Type: OTHER

Watch and wait strategy recommendation and discussion for cCR patients

Interventions

Capecitabine, Oxaliplatin

Drug: Capecitabine, Oxaliplatin

Intervention Type: DRUG

External beam radiotherapy

External beam radiotherapy to the primary tumor, regional lymph nodes and clinical target volume

Intervention Type: RADIATION

Surgery

'Local excision' or 'Intersphincter resection' or 'Total mesorectal excision' or other surgeries

Intervention Type: PROCEDURE

Watch and wait strategy

Watch and wait strategy recommendation and discussion for cCR patients

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

WeiWei Xiao

Associate professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

WeiWei Xiao

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Countries

China

Other Identifiers

5010-2018-04

Identifier Type: OTHER

Identifier Source: secondary_id

2018-FXY-149

Identifier Type: -

Identifier Source: org_study_id