Clinical trial NCT06204094: Node-sparing Radiotherapy Combined with Total Neoadjuvant CAPOX and Sintilimab for MSS Middle and Low Rectal Cancer
Official title: Total Neoadjuvant CAPOX and PD-1 Inhibitor（Sintilimab） Combined with Node-sparing Short-course Radiotherapy for MSS Locally Advanced of Middle and Low Rectal Cancer(CASINOs): an Open Label, Single-arm, Prospective Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Locally Advanced Rectal Cancer
Keywords: rectal cancer
microsatellite stability
node-sparing
CAPOX
radiotherapy
sintilimab
immunotherapy
neoadjuvant
Lead sponsor: Jinhua Central Hospital
Sponsor class: OTHER
First posted: 2024-01-12
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Radiation: node-sparing short-course radiotherapy (5Gy\*5d) Drug: PD-1 antibody (Sintilimab) Drug: Capecitabine Drug: Oxaliplatin
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Complete response
timeFrame: within 10 days after TNT therapy or surgery
Secondary outcomes:
measure: Tumor regression grade
timeFrame: within 10 days after surgery
measure: Local recurrence rate(LRR)
timeFrame: 3 years after sugery
measure: Disease free survival(DFS)
timeFrame: 3 years after treatment
measure: Overall survival(OS)
timeFrame: 3 years after enrollment
measure: Adverse effects rate
timeFrame: From date of initiation of treatment until the date of death from any cause, assessed up to 5 years
measure: Rectal specific quality of life assessment via QLQ-CR29
timeFrame: Baseline and months 3, 6, 12, 24, 36, 60 after the TNT treatment or surgery
measure: Quality of life assessment via QLQ-C30
timeFrame: Baseline and months 3, 6, 12, 24, 36, 60 after the TNT treatment or surgery
measure: Validation of the Wexner score
timeFrame: Months 3, 6, 12, 24, 36, 60 after the TNT treatment or surgery
Other outcomes:
Locations:
city: Jinhua
country: China
facility: Zhejiang University Affiliated Jinhua Hospital
state: Zhejiang
Study officials:
References: