Treating Locally Advanced Rectal Cancer With TAS-102 Chemotherapy Plus Neoadjuvant Radiotherapy (TASLARC)

A Single-arm, Phase II Clinical Trial to Treat Locally Advanced, pMMR Rectal Cancer With Single-agent Trifluridine/Tipiracil Chemotherapy Plus Neoadjuvant Intensity-modulated Radiotherapy

The goal of this Phase 2 trial is to evaluate a neoadjuvant treatment mode for locally advanced rectal cancer (LARC), consisting of radiotherapy and concurrent Trifluridine/Tipiracil (TAS-102). The main questions it aims to answer are: (i) whether TAS-102 is effective in treating LARC, when combined with radiotherapy; (ii) whether TAS-102 is safe in combination with radiotherapy. Participants will receive one cycle of TAS-102 chemotherapy and neoadjuvant radiotherapy based on intensity-modulated technique. Then the ones with a possibility of R0 resection will receive radical surgery followed by 6 cycles of adjuvant XELOX (capecitabine plus oxaliplatin) chemotherapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: Trifluridine/Tipiracil; Radiation: intensity-modulated radiotherapy

Detailed Description

The standard management recommended by the National Comprehensive Cancer Network for locally advanced rectal cancer (LARC) is neoadjuvant chemo-radiotherapy followed by surgery plus adjuvant chemotherapy or not. Currently, the regimens of neoadjuvant chemotherapy are based on fluorouracil or capecitabine. The therapeutic effects of these regimens are satisfactory, with a pathological complete response (pCR) and 3-year disease-free survival (DFS) rate of 14% and 68%. Addition of oxaliplatin has been proven to further improve the pCR and DFS rates, by the CAO/ARO/AIO-04, FOWARC and ADORE trials. However, the acute toxicities of fluorouracil and capecitabine remain as a concern. It was reported that the incidence of the grade 3/4 symptomatic toxicities brought by these two agents was nearly 15%. When combined with oxaliplatin, the incidence could rise to 25%. A special toxicity, hand-foot syndrome, was seen in 43-71% of the patients receiving capecitabine. It included blister, ulceration, numbness, pain and paresthesia, and seriously influenced the daily work and life of the patients. Trifluridine/Tipiracil (TAS-102) is a new generation of cytotoxic agent whose therapeutic effects in metastatic colorectal cancer have been confirmed by a series of large-scale, multicenter, randomized controlled trials. And the latest TASCO1 trial reported that TAS-102 exhibited a trend to improve overall survival, compared to capecitabine. Moreover, it could be well tolerated, with an incidence of grade 3/4 symptomatic toxicities of merely 1.5%. Until now, there was few study focusing on combination of TAS-102 and radiotherapy. This phase 2 trial intended to evaluate the therapeutic and adverse effects of TAS-102 concurrently with neoadjuvant radiotherapy, in a small patient cohort with LARC. The results might provide an effective and low-toxic choice which improves patients' experience of chemo-radiotherapy.

• Study Type: Interventional
• Enrollment (Estimated): 65
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hui Chang, MD; Phone Number: +86-020-87343374; Email: changhui@sysucc.org.cn
• Study Contact Backup: Name: Qiao-xuan Wang, MD; Phone Number: +86-020-87343374; Email: wangqx@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Cancer Center, Sun Yat-sen University
      • Contact: Hui Chang, MD; Phone Number: +86-020-87343374; Email: changhui@sysucc.org.cn
      • Contact: Qiao-xuan Wang, MD; Email: wangqx@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pathologically diagnosed rectal adenocarcinoma via biopsy
• Pretreatment clinical TNM stage as T3-4N0M0 or T1-4N1-2M0 (UICC TNM staging classification, version 8)
• Tumor with proficient DNA mismatch repair confirmed by immunohistochemical analysis
• Age between 18 and 70 years old
• Karnofsky performance score ≥ 70
• Distance from tumor lower margin to anal verge < 12 cm

Exclusion Criteria:

• Inguinal lymph node metastasis
• Multiple primary colorectal cancer
• Complete obstruction or perforation
• Uncontrolled tuberculosis, AIDS or mental diseases
• Severe cardiac, renal, hepatic or hematopoietic dysfunctions unsuitable for chemotherapy or radiotherapy
• Prior history of other malignancies with 5 years, except cured cervical carcinoma in situ and skin basal cell carcinoma
• Prior history of rectal surgery, pelvic radiotherapy or chemotherapy
• Pregnant or lactating women
• Other situations for which the investigators consider a patient inappropriate to participate

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: Neoadjuvant chemo-radiotherapy with TAS-102; The patients in this group will all receive neoadjuvant treatment consisting of intensity-modulated radiotherapy and concurrent Trifluridine/Tipiracil (TAS-102). Then the ones evaluated to have a possibility of R0 resection will receive radical surgery, followed by 6 cycles of adjuvant XELOX (capecitabine plus oxaliplatin) chemotherapy.	Drug: Trifluridine/Tipiracil; TAS-102 is given in a dose of 35 mg/m2, twice daily on the 1st to 5th and 8th to 12th days of the period of neoadjuvant radiotherapy.; Other Names: TAS-102; Radiation: intensity-modulated radiotherapy; intensity-modulated radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	The percentage of the patients complete R0 resection and attain a tumor regression grade of 1-4 (Mandard's 5-tier standard) in postsurgical pathologic examination	One week after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response rate	The percentage of the patients complete R0 resection and attain a complete remission of both primary tumor and regional lymph nodes in postsurgical pathologic examination	One week after surgery
The incidence of grade 3/4 toxicities	The percentage of the patients undergo any grade 3/4 toxicity during neoadjuvant treatment, based on the Common Terminology Criteria for Adverse Events	Once a week during the period of neoadjuvant treatment
The incidence of grade 3/4 complications	The percentage of the patients undergo any grade 3/4 surgery-related complication, based on the Clavien-Dindo classification.	The period from the date of radical surgery to the 90th day after surgery
Disease-free survival	The percentage of the patients survive without local recurrence or distant metastasis after a time period, from pathological diagnosis	When all the patients are followed-up for 1, 2 and 5 years
Overall survival	The percentage of the patients survive after a time period, from pathological diagnosis	When all the patients are followed-up for 1, 2 and 5 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Hui Chang, MD, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2023
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: July 14, 2023
• First Submitted That Met QC Criteria: July 27, 2023
• First Posted (Actual): July 28, 2023

Study Record Updates

• Last Update Posted (Actual): October 31, 2023
• Last Update Submitted That Met QC Criteria: October 29, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: radiotherapy; rectal cancer; Trifluridine/Tipiracil
• 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; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Trifluridine
• Other Study ID Numbers: 2023-FXY-087

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No