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

Total Neoadjuvant trEatment to Increase the Clinical Complete reSponse Rate for diStal Locally Advanced Rectal Cancer (TESS)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Chemoradiation; Rectal Cancer; Rectal Cancer Stage II; Rectal Cancer Stage III
• Intervention / Treatment: Drug: Capecitabine, Oxaliplatin; Radiation: External beam radiotherapy; Procedure: Surgery; Other: Watch and wait strategy

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 Type: Interventional
• Enrollment (Estimated): 98
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: WeiWei xiao; Phone Number: 8613710390520 8613710390520; Email: xiaoww@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of clinical complete response	Rate of clinical complete response	1.5 year after diagnosis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ratio of sphincter preservation strategy	Number of patients with sphincter preservation through Watch and wait strategy, or local excision, or intersphincter resection, or low anterior resection, etc.	1.5 year after diagnosis
Rate of pathological complete response and tumor regression grade distribution	Rate of pathological complete response and tumor regression grade distribution	1.5 year after diagnosis
Acute toxicity	Acute toxicity according to CTCAE 5.0	Within the first course of anti-tumor treatment
Rate of surgical complications	Rate of surgical complications	1.5 year after diagnosis
Long-term anal function	Long-term anal function according to Wexner Continence Grading Scale	1.5 year after diagnosis
Long-term toxicity grading	Long-term toxicity grading according to CTCAE 5.0	3 year after the end of the first course of anti-tumor treatment
ECOG standard score	ECOG standard score	1.5 year after diagnosis
3 year disease free survival	3 year disease free survival	3 year after the end of the first course of anti-tumor treatment
5 year overall survival	5 year overall survival	5 year after the end of the first course of anti-tumor treatment

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Weiwei Xiao, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): December 25, 2018
• Primary Completion (Estimated): December 30, 2023
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: January 28, 2019
• First Submitted That Met QC Criteria: February 12, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Actual): October 25, 2023
• Last Update Submitted That Met QC Criteria: October 24, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: rectal cancer; chemoradiation; total neoadjuvant treatment
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine; Oxaliplatin
• Other Study ID Numbers: 2018-FXY-149; 5010-2018-04 (Other Identifier: Sun Yat-sen University Cancer Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No