Rectal Cancer
Conditions
Keywords
rectal cancer, Trifluridine/Tipiracil, radiotherapy
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.
Interventions
DRUGTrifluridine/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.
RADIATIONintensity-modulated radiotherapy
intensity-modulated radiotherapy
Sponsors
Sun Yat-sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
China
Contacts
Primary ContactHui Chang, MD
Backup ContactQiao-xuan Wang, MD
Outcome results
None listed