Locally Advanced Rectal Cancer
Conditions
Keywords
rectal cancer, microsatellite stability, node-sparing, CAPOX, radiotherapy, sintilimab, immunotherapy, neoadjuvant
Brief summary
phase II clinical trial to evaluate node-sparing short-course radiation combined with total neoadjuvant CAPOX and Sintilimab for MSS locally advanced rectal cancers.
Detailed description
This is an open-label, prospective, single-center phase II clinical trial to evaluate node-sparing short-course radiation (Radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) combined with total neoadjuvant CAPOX and PD-1 Inhibitor (Sintilimab) for patients with MSS locally advanced of middle and low rectal cancer. A total of 47 patients will be enrolled in this trial. The primary endpoint is the complete response(CR) rate, which includes cCR and pCR. The organ preservation rate, tumor regression grade, 3-year DFS, 3-year OS, and adverse effects will also be analyzed.
Interventions
RADIATIONnode-sparing short-course radiotherapy
5Gy\*5d, radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes
DRUGSintilimab
200mg intravenous infusion d1 of each cycle\*8cycles
DRUGCapecitabine
1000mg/m2, PO, BID, d1-14 of each cycle\*8cycles
DRUGOxaliplatin
130mg/m2, intravenous infusion,d1 of each cycle\*8cycles
PROCEDURETME surgery
laparoscopic or robotic TME surgery for non-cCR patients
PROCEDUREwatch and wait
WW for cCR patients
Sponsors
Jinhua Central Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Radiation: node-sparing short-course radiotherapy (5Gy\*5d) Drug: PD-1 antibody (Sintilimab) Drug: Capecitabine Drug: Oxaliplatin
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients who have a strong willingness to preserve the anus and are willing to receive neoadjuvant therapy. * Male or Female aged 18-75. * Patients diagnosed with low rectal cancer within 10 cm from the lower edge of the tumor to the anal verge by pelvic MRI and anorectoscopy, the clinical stage is cT2N+M0/cT3-4aN0/+M0, the lymph nodes are limited to the mesorectum, the circumferential resection margin is negative. * Histologically confirmed rectal adenocarcinoma; Genetic testing suggests MSI-L or MSS, or tumor biopsy immunohistochemistry reveals pMMR, that is, MSH1, MSH2, MSH6, and PMS2 are all positive. * Eastern Cooperative Oncology Group (ECOG) 0-1. * No previous treatment(including anti-tumor therapy、immunotherapy or pelvic radiation). * Adequate hematologic, hepatic, renal, thyroid and cardiac function: white blood cells ≥3500/mm3, neutrophils ≥1800/mm3, platelets ≥100,000/mm3, hemoglobin ≥100 g/L; activated partial thromboplastin time, prothrombin time and international normalized ratio ≤1.5 × ULN; aspartate aminotransferase and alanine aminotransferase ≤3.0 × upper limit of normal (ULN), bilirubin ≤1.25 × ULN, serum albumin ≥28 g/L. creatinine clearance ≥50 mL/mi, creatinine ≤1.5 × ULN; * Informed consent form signed.
Exclusion criteria
* Patients with a previous history of malignant tumors besides rectal cancer. * Patients with distant metastases before enrollment. * Patients with positive internal or external iliac lymph nodes are assessed by MRI or CT. * Patients with obstruction, perforation, or bleeding that require emergency surgery. * Patients with severe concomitant diseases and estimated survival time ≤ 5 years. * Allergic to any component of the therapy. * Patients with poorly differentiated adenocarcinoma, signet ring cell carcinoma, or mucinous adenocarcinoma. * Patients who received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to the initiation of therapy. * Patients who have received any other experimental drug (including immunotherapy) or participated in another interventional clinical trial within 30 days before screening. * Factors leading to study termination, such as alcoholism, drug abuse, other serious illnesses (including psychiatric disorders) requiring combination therapy, and patients with severe laboratory abnormalities. * Patients with congenital or acquired immune deficiency (such as HIV infection). * Vulnerable groups, including mentally ill, cognitively impaired, critically ill patients, minors, pregnant or lactating women, illiterate, etc. Other conditions that investigators consider not suitable for this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete response | within 10 days after TNT therapy or surgery | Pathological complete response (pCR) ：absence of residual tumour on resected specimen. Clinical complete response（cCR）: no residual tumour visible on imaging or colonoscopy and biopsy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tumor regression grade | within 10 days after surgery | TRG is evaluated according to the AJCC system. TRG0-1 is defined as good response, TRG2 as moderate response, and TRG3 as poor response. |
| Local recurrence rate(LRR) | 3 years after sugery | Presence of adenocarcinoma within the rectal wall or within the mesorectum confirmed by pathology. |
| Disease free survival(DFS) | 3 years after treatment | the time from randomization to recurrence of tumor or death |
| Adverse effects rate | From date of initiation of treatment until the date of death from any cause, assessed up to 5 years | Rate of radiotherapy, chemotherapy and immunotherapy related adverse events |
| Rectal specific quality of life assessment via QLQ-CR29 | Baseline and months 3, 6, 12, 24, 36, 60 after the TNT treatment or surgery | Rectal specific quality of life according to European Organization for Research and Treatment of Cancer ( EORTC) Quality of life questionnaire QLQ-CR29. scale from 0 to 100, A higher scale represents better function and a higher quality of life. |
| Quality of life assessment via QLQ-C30 | Baseline and months 3, 6, 12, 24, 36, 60 after the TNT treatment or surgery | Quality of life according to EORTC Quality of life Questionnaire QLQ-C30 version 3.0. Score range from 0 to 100 points. A higher score represents better function and a higher quality of life. |
| Validation of the Wexner score | Months 3, 6, 12, 24, 36, 60 after the TNT treatment or surgery | The change of severity of fecal incontinence assessment according to Wexner score. a score from 0-20, where 0 is perfect continence and 20 is complete incontinence. |
| Overall survival(OS) | 3 years after enrollment | the time from randomization to death |
Countries
China
Contacts
Primary Contactjinlin du, master
Backup Contactcheng cai, master
Outcome results
None listed