Clinical trial NCT05965531: Treating Locally Advanced Rectal Cancer With TAS-102 Chemotherapy Plus Neoadjuvant Radiotherapy
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: rectal cancer
Trifluridine/Tipiracil
radiotherapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2023-07-28
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This phase 2 trial is an open-label, single-arm, non-comparative trial, in which all enrolled patients will receive neoadjuvant single-agent TAS-102 chemotherapy plus intensity-modulated radiotherapy, before surgery.
Primary purpose: TREATMENT

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.

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.

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 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

Primary outcomes:
measure: Objective response rate
timeFrame: One week after surgery
Secondary outcomes:
measure: Pathological complete response rate
timeFrame: One week after surgery
measure: The incidence of grade 3/4 toxicities
timeFrame: Once a week during the period of neoadjuvant treatment
measure: The incidence of grade 3/4 complications
timeFrame: The period from the date of radical surgery to the 90th day after surgery
measure: Disease-free survival
timeFrame: When all the patients are followed-up for 1, 2 and 5 years
measure: Overall survival
timeFrame: When all the patients are followed-up for 1, 2 and 5 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Cancer Center, Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Hui Chang, MD
role: PRINCIPAL_INVESTIGATOR
References: