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

Sponsor

Sun Yat-sen University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05965531

Collaborator

(none)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Rectal Cancer	Drug: Trifluridine/Tipiracil Radiation: intensity-modulated radiotherapy	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

65 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This study adopts the Simon's optimal two-stage design and uses the objective response rate (ORR) as the primary endpoint. The first stage will enroll 19 eligible patients. If the observed ORR > 70%, the study will enter the second stage and continue to enroll 40 eligible patients. The final sample size is 65 when a drop-out rate of 10% is considered.This study adopts the Simon's optimal two-stage design and uses the objective response rate (ORR) as the primary endpoint. The first stage will enroll 19 eligible patients. If the observed ORR > 70%, the study will enter the second stage and continue to enroll 40 eligible patients. The final sample size is 65 when a drop-out rate of 10% is considered.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Dec 31, 2028

Anticipated Study Completion Date :

Dec 31, 2028

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Objective response rate [One week after surgery]
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

Secondary Outcome Measures

Pathological complete response rate [One week after surgery]
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
The incidence of grade 3/4 toxicities [Once a week during the period of neoadjuvant treatment]
The percentage of the patients undergo any grade 3/4 toxicity during neoadjuvant treatment, based on the Common Terminology Criteria for Adverse Events
The incidence of grade 3/4 complications [The period from the date of radical surgery to the 90th day after surgery]
The percentage of the patients undergo any grade 3/4 surgery-related complication, based on the Clavien-Dindo classification.
Disease-free survival [When all the patients are followed-up for 1, 2 and 5 years]
The percentage of the patients survive without local recurrence or distant metastasis after a time period, from pathological diagnosis
Overall survival [When all the patients are followed-up for 1, 2 and 5 years]
The percentage of the patients survive after a time period, from pathological diagnosis

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Sun Yat-sen University

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hui Chang, Professor, Sun Yat-sen University

ClinicalTrials.gov Identifier:

NCT05965531

Other Study ID Numbers:

2023-FXY-087

First Posted:

Jul 28, 2023

Last Update Posted:

Jul 28, 2023

Last Verified:

Jul 1, 2023

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Hui Chang, Professor, Sun Yat-sen University

rectal cancer

Trifluridine/Tipiracil

radiotherapy

Additional relevant MeSH terms:

Rectal Neoplasms

Trifluridine

Study Results

No Results Posted as of Jul 28, 2023