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

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

NCT ID: NCT05965531

Condition: Rectal Cancer

Conditions: Official terms:
Rectal Neoplasms
Trifluridine

Conditions: Keywords:
rectal cancer
Trifluridine/Tipiracil
radiotherapy

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

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.

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Trifluridine/Tipiracil
Description: 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.
Arm group label: Neoadjuvant chemo-radiotherapy with TAS-102

Other name: TAS-102

Intervention type: Radiation
Intervention name: intensity-modulated radiotherapy
Description: intensity-modulated radiotherapy
Arm group label: Neoadjuvant chemo-radiotherapy with TAS-102

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.

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.

Criteria for eligibility:
Criteria:
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

Gender: All

Minimum age: 18 Years

Maximum age: 70 Years

Healthy volunteers: No

Locations:

Facility:
Name: Cancer Center, Sun Yat-sen University

Address:
City: Guangzhou
Zip: 510060
Country: China

Contact:
Last name: Hui Chang, MD

Phone: +86-020-87343374
Email: changhui@sysucc.org.cn

Contact backup:
Last name: Qiao-xuan Wang, MD
Email: wangqx@sysucc.org.cn

Start date: November 1, 2023

Completion date: December 31, 2028

Lead sponsor:
Agency: Sun Yat-sen University
Agency class: Other

Source: Sun Yat-sen University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05965531