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
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Enrollment
- 65
- Locations
- 1
- Primary Endpoint
- Objective response rate
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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.
Intervention: Trifluridine/Tipiracil (Drug)
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.
Intervention: intensity-modulated radiotherapy (Radiation)
Outcomes
Primary Outcomes
Objective response rate
Time Frame: 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 Outcomes
- The incidence of grade 3/4 complications(The period from the date of radical surgery to the 90th day after surgery)
- Pathological complete response rate(One week after surgery)
- Overall survival(When all the patients are followed-up for 1, 2 and 5 years)
- The incidence of grade 3/4 toxicities(Once a week during the period of neoadjuvant treatment)
- Disease-free survival(When all the patients are followed-up for 1, 2 and 5 years)
Investigators
Hui Chang
Professor
Sun Yat-sen University