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

Sun Yat-sen University

Status and phase: Enrolling; Phase 2

Conditions: Rectal Cancer

Treatments: Drug: Trifluridine/Tipiracil; Radiation: intensity-modulated radiotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT05965531

2023-FXY-087

Details and patient eligibility

About

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.

Full 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.

Enrollment: 65 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No 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 75 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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65 participants in 1 patient group

Neoadjuvant chemo-radiotherapy with TAS-102

Experimental group

Description:

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.

Treatment:

Radiation: intensity-modulated radiotherapy

Drug: Trifluridine/Tipiracil