Colorectal Neoplasms
Conditions
Keywords
Colorectal Neoplasms, Programmed Cell Death 1 Receptor, Neoadjuvant Therapy
Brief summary
Long course radiotherapy plus neoadjuvant chemotherapy followed by resection total mesorecta excision has accepted widespread recognized in the treatment of locally advanced rectal cancer (LARC). Tislelizumab, an anti-PD1(programmed death 1) humanized IgG4 (Immunoglomin G4) monoclonal antibody, has been demonstrated with clinical activity and is approved for treating recurrent/refractory classical Hodgkin lymphoma and locally advanced/metastatic urothelial carcinoma in China. The aim of This NCRT-PD-1-LARC trial is to evaluate the efficacy and safety of long course neoadjuvant chemoradiotherapy plus tislelizumab followed by total mesorecta excision for LARC. This NCRT-PD-1-LARC trial will be a prospective, multicenter and phase Ⅱ clinical trial designed to evaluate the safety and efficacy of LARC patients treated with long course neoadjuvant chemoradiotherapy plus tislelizumab followed by total mesorecta excision. It will consecutively enroll 50 stage II/III LARC patients (cT3N0M0 and cT1-3N1-2M0) with the tumor distal location ≤ 10cm from anal verge at 7 centers in China. The enrolled patients will receive long course radiotherapy (50 Gy/25 f, 2 Gy/f, 5 days/week) and three 21-day cycles capecitabine (1000 mg/m2, bid, po, day1-14) plus three 21-day cycles tislelizumab (200 mg, iv.gtt, day8), followed by total mesorecta excision 6-12 week after the end of radiotherapy. The primary efficacy endpoint will be the pathological complete response (pCR) rate, which is defined as absence of viable tumor cells in the primary tumor and lymph nodes.
Interventions
COMBINATION_PRODUCTlong course radiotherapy + capecitabine + PD-1 monoclonal antibody treatment combinations
long course radiotherapy + capecitabine + PD-1 monoclonal antibody treatment combinations in patients with locally advanced rectal cancer
Sponsors
Hangzhou New Horizon Health Technology Co., Ltd.
BeOne Medicines
Beijing Chao Yang Hospital
Xuanwu Hospital, Beijing
Tianjin Medical University General Hospital
People's Hospital of Tianjin
Tianjin Medical University Cancer Institute and Hospital
Beijing Friendship Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The enrolled patients in this NCRT-PD-1-LARC trial will receive long course radiotherapy (50 Gy/25 f, 2 Gy/f, 5 days/week) and three 21-day cycles capecitabine (1000 mg/m2, bid, po, day1-14) plus three 21-day cycles tislelizumab (200 mg, iv.gtt, day8), followed by total mesorecta excision 6-8 week after the end of radiotherapy.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients have been fully aware of the content of this study and signed the informed consent voluntarily; * Patients with rectal cancers must satisfied all the following conditions: Stage II/III LARC (cT1-3N1-2M0)；Tumor distal location ≤10 cm from anal verge (MRI diagnosed); * Patients regardless of gender with aged ≥18 years and ECOG score of 0 or 1; * Physical and viscera function of patients can withstand major abdominal surgery; * Patients are willing and able to follow the study protocol during the study; * Patients give consent to the use of blood and pathological specimens for study; * Within 28 days prior to enrolment, we must confirm a negative serological pregnancy test for child-bearing age women and they agree to use effective contraception for the duration of drug use and for 60 days after the last dose.
Exclusion criteria
* Patients have a present or previous active malignancy except the diagnosis of rectal cancer this time; * Patients underwent major surgery within 4 weeks prior to study treatment; * Patients have any condition affects the absorption of capecitabine through gastrointestinal tract; * Patients have severe uncontrolled recurrent infections, or other severe uncontrolled concomitant diseases; * Patients who are allergic to any of the ingredients under study; * Patients with severe concomitant diseases with estimated survival ≤ 5 years; * Patients with present or previous moderate or severe liver and kidney damage presently or previously; * Patients have received other study medications or any immunotherapy currently or in the past; * Patients preparing for or previously received organ or bone marrow transplant; * Patients who received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to the initiation of study therapy; * Patients with congenital or acquired immune deficiency (such as HIV infection); * If patients with a history of uncontrolled epilepsy, central nervous system disease or mental disorder, the investigator will determine whether the clinical severity prevents the signing of informed consent or affects the patient's oral medication compliance; * Patients with other factors that may affect the study results or cause the study to be terminated midway, such as alcoholism, drug abuse, other serious diseases (including mental illness) requiring combined treatment and severe laboratory examination abnormalities. * Pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pathologic complete response（pCR） | 1 year | All the enrolled patients will receive total mesorectal excision (TME) 7-9 weeks after the end of long course radiotherapy. The rectal specimens will be evaluated by the pathologists who are experienced on the rectal cancer diagnosis according to the 1997 Dworak grading system. The rectal cancer will be classified into 5 grades. Grade 0-3 will be considered as non-pCR while grade 4 represent pCR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| objective response rate (ORR) | 1 year | ORR is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The ORR rate is the sum of complete response (CR) and partial response (PR) |
| R0 resection rate | 1 year | During the surgical process, the surgeon will evaluate the level of cancer resection. It will be classified as R0, R1, R2 resection. Therefore, we can calculate R0 resection rate. |
| anal preservation rate | 1 year | the surgeon will decide whether the anal can be preserved on the basis of the rectal cancer and intraoperative situation. anal preservation rate is the percentage of patients who achieve anal preservation. |
| neoadjuvant rectal (NAR) score | 1 year | The neoadjuvant rectal (NAR) score is a promising indicator of survival after preoperative chemoradiotherapy for rectal cancer. The NAR score was calculated according to the following formula: NAR score = \[5pN - 3(cT - pT) + 12\]2∕9.61. (clinical tumor (cT) stage, pathologic tumor (pT) stage, pathologic nodal (pN) stage) |
| 3-year disease free survival (DFS) | 3 year | During the 3-year follow-up, the percentage of the patients who is disease free. |
| 3-year overall survival (OS) | 3 year | During the 3-year follow-up, the percentage of the patients who is sill survival at the end of follow-up. |
| 3-year local recurrence rate (LRR) | 3 year | During the 3-year follow-up, the percentage of local recurrence. |
Countries
China
Contacts
Primary ContactHongwei Yao, Dr.
Outcome results
None listed