Trial Title:
Node-Sparing Short-Course Radiation with CAPOX and Sintilimab for MSS Locally Advanced Colon Cancer: a Randomized, Prospective, Multicenter Study
NCT ID:
NCT06594692
Condition:
Microsatellite Stable (MSS) Colon Cancer
Locally Advanced Colon Cancer
Conditions: Official terms:
Colonic Neoplasms
Conditions: Keywords:
Locally Advanced Colon Cancer
Microsatellite Stable (MSS) Colon Cancer
Node-Sparing Radiotherapy
Short-Course Radiotherapy
Sintilimab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Node-Sparing Short-Course Radiotherapy Combined with CAPOX and Sintilimab
Description:
Radiotherapy Protocol:
Short-course radiotherapy using three-dimensional conformal or intensity-modulated
radiation therapy techniques. The radiation field will be limited to the tumor bed of the
primary colon lesion, excluding surrounding draining lymph nodes and enlarged lymph
nodes. The dose is fractionated as 5Gy per fraction, for a total of 25Gy over 5
fractions. Titanium clips will be placed on the proximal and distal ends of the colonic
lesion via colonoscopy to guide radiation therapy positioning.
Chemotherapy Protocol (CAPOX Regimen):
1. Oxaliplatin: 130 mg/m², administered intravenously (ivgtt), on day 1 (d1).
2. Capecitabine: 1000 mg/m², orally (po), twice daily (bid), from day 1 to day 14
(d1-14).
Immunotherapy Protocol:
During preoperative treatment, Sintilimab (immune checkpoint inhibitor) will be
administered concurrently with each chemotherapy cycle.
Arm group label:
Node-Sparing Short-Course Radiotherapy Combined with CAPOX and Sintilimab
Intervention type:
Drug
Intervention name:
CAPOX Chemotherapy
Description:
Participants will receive 4 cycles of CAPOX chemotherapy followed by radical total
mesorectal excision surgery, and then 4 additional cycles of postoperative CAPOX
chemotherapy.
Arm group label:
Preoperative CAPOX Regimen as Neoadjuvant Therapy
Summary:
This study aims to evaluate the use of node-sparing short-course radiotherapy combined
with chemotherapy and Sintilimab, or chemotherapy alone, as neoadjuvant therapy for
MSS-type locally advanced colon cancer. The goal is to explore the efficacy and safety of
combining node-sparing short-course radiotherapy with chemotherapy and immunotherapy in
the neoadjuvant setting for MSS-type locally advanced colon cancer, while also
investigating the specific role of regional lymph nodes in tumor immunotherapy.
Detailed description:
Colorectal cancer is currently one of the most common malignant tumors in China.
According to the latest data released by the National Cancer Center, it ranks second in
incidence and fourth in mortality among all cancer types. Statistics indicate that
approximately 50% of colon cancer patients in China are in stages II-III. Currently,
adjuvant chemotherapy regimens containing oxaliplatin and 5-fluorouracil are the standard
treatment for stage III and high-risk stage II colon cancer patients. However, under
standard treatment protocols, the 5-year disease-free survival (DFS) rate for stage III
colon cancer is less than 64%, with a recurrence rate exceeding 20%. Patients with higher
T and N stages face a significantly increased risk of recurrence, severely impacting
survival rates and imposing a substantial burden on both the healthcare system and
society.
Neoadjuvant chemotherapy, which is administered before surgery, offers several
theoretical advantages, including shrinking the primary tumor to improve surgical
resection rates, reducing intraoperative tumor cell spread, and eliminating
micrometastases and subclinical lesions to lower the risk of postoperative metastasis.
However, data on neoadjuvant chemotherapy for locally advanced colon cancer remains
limited. The FOxTROT study found that preoperative neoadjuvant chemotherapy significantly
reduced the 2-year recurrence rate for locally advanced colon cancer, achieved tumor
downstaging, and provided a 4% pathological complete response (pCR) rate. This study also
demonstrated a strong correlation between pathological response to neoadjuvant therapy
and recurrence risk, with patients achieving pCR or major pathological response (mPR)
having significantly lower recurrence rates.
Recent studies have shown that combining immunotherapy with radiotherapy has a
synergistic effect, even in MSS-type colorectal cancer patients. Radiotherapy can induce
immunogenic cell death, releasing tumor-associated antigens and enhancing the function of
dendritic cells, thereby increasing T-cell infiltration. Moreover, chemotherapy can alter
the tumor microenvironment, promote angiogenesis, and improve oxygen distribution,
further enhancing the efficacy of radiotherapy. One prospective phase II clinical trial
involving locally advanced rectal cancer patients showed promising results, with a pCR
rate of 46.2% in patients with proficient mismatch repair (pMMR), suggesting a favorable
response to neoadjuvant therapy.
Lymph nodes, as secondary lymphoid organs, play a crucial role in tumor diagnosis and
treatment. Recent preclinical studies have shown that tumor-draining lymph nodes (TDLNs)
are essential in antigen activation and effector T-cell differentiation. On the other
hand, tertiary lymphoid structures (TLS), which are organized immune cell aggregates
formed in non-lymphoid tissues, have been associated with improved prognosis in cancer
patients. However, the role of TDLNs in immunotherapy remains underexplored.
Based on these findings, the research team hypothesizes that tumor-draining lymph nodes
play a positive role in immunotherapy response, and sparing these nodes during
radiotherapy may enhance the efficacy of immunotherapy for MSS-type colorectal cancer.
The team previously conducted a phase II clinical study (NCT04503694) investigating the
safety and efficacy of node-sparing short-course radiotherapy combined with CAPOX
chemotherapy and PD-1 inhibitors in MSS-type locally advanced rectal cancer. Results
showed a 100% response rate to neoadjuvant therapy, with a pCR rate of 78.8% and a major
pathological response (mPR) rate of 91%, while maintaining a high rate of organ
preservation.
Given the high recurrence rates and treatment challenges associated with locally advanced
colon cancer, and building on the promising results of previous studies, the research
team intends to conduct the mRCAT-C study. This study aims to explore the clinical
efficacy and safety of a node-sparing short-course radiotherapy combined with
immunotherapy as a neoadjuvant treatment for MSS-type locally advanced colon cancer.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
-
1. Patients willing to undergo neoadjuvant treatment. 2. Age ≥ 18 years. 3. Tumor
confirmed by colonoscopy and enhanced abdominal CT to be ≥ 12 cm from the anal
verge.
4. Histologically diagnosed adenocarcinoma; genetic testing indicates MSI-L or
MSS, or immunohistochemistry from tumor biopsy shows pMMR (all four
proteins-MSH1, MSH2, MSH6, and PMS2-are positive).
5. Clinical staging by enhanced abdominal CT evaluates as cT3-4N0-2M0. 6. ECOG
performance status score of 0-1. 7. No prior treatment with anti-tumor,
immunotherapy, or abdominal radiation therapy before enrollment.
8. Blood test results (without transfusion within 14 days and no use of
granulocyte colony-stimulating factor or other hematopoietic stimulators within
7 days before the lab test):
1. White blood cell count ≥ 3.5 × 10^9/L, absolute neutrophil count ≥ 1.5 ×
10^9/L, platelet count ≥ 100 × 10^9/L, hemoglobin concentration ≥ 9 g/dL;
2. Liver function tests (bilirubin ≤ 1.5 × ULN; AST and ALT ≤ 5 × ULN);
3. Renal function (serum creatinine ≤ 1.5 × ULN or creatinine clearance (CCr) ≥ 50
mL/min);
4. Coagulation (INR ≤ 1.5 × ULN, PT and APTT ≤ 1.5 × ULN);
5. Thyroid function: TSH ≤ upper limit of normal (ULN); if abnormal, FT3 and FT4
levels must be evaluated, and if FT3 and FT4 are normal, the patient is
eligible.
9. Voluntary participation with a signed informed consent form.
Exclusion Criteria:
-
1. History of other malignancies within the past 5 years. 2. Patients with
metastases in other locations (stage IV). 3. Patients with MSI-H or dMMR. 4.
Patients with conditions such as bowel obstruction, perforation, or bleeding
requiring emergency surgery.
5. Known allergy to the study drug or any of its excipients. 6. Patients with any
unstable systemic diseases, including but not limited to severe infections,
uncontrolled diabetes, uncontrolled hypertension, unstable angina,
cerebrovascular accidents or transient ischemic attacks, myocardial infarction,
congestive heart failure, or severe illnesses requiring medication (such as
arrhythmias, liver, kidney, or metabolic diseases) that are life-threatening.
7. History of active autoimmune diseases requiring systemic treatment (e.g.,
disease-modifying drugs, corticosteroids, or immunosuppressants) within the
last 2 years. Replacement therapies (e.g., thyroid hormone, insulin, or
physiological corticosteroid replacement for adrenal or pituitary
insufficiency) are not considered systemic treatments.
8. Known history of HIV infection or acquired immunodeficiency syndrome (AIDS). 9.
Receipt of any investigational drug (including immunotherapy) or participation
in another interventional clinical study within 30 days before screening.
10. Pregnant or breastfeeding women, or women planning to become pregnant or
breastfeed during the study; men or women unwilling to use effective
contraception during the study.
11. Vulnerable populations, including those with mental illness, cognitive
impairment, or critically ill patients.
12. Any other conditions deemed inappropriate for participation by the
investigator.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Sir Run Run Shaw Hospital, Zhejiang University
Address:
City:
Hangzhou
Zip:
310016
Country:
China
Contact:
Email:
chenengeng@zju.edu.cn
Facility:
Name:
Sir Run Run Shaw Hospital, Zhejiang University
Address:
City:
Hangzhou
Zip:
310016
Country:
China
Contact:
Last name:
Zhangfa Song, Ph.D.;M.D.
Phone:
+86 13867421652
Email:
songzhangfa@zju.edu.cn
Start date:
October 2024
Completion date:
September 30, 2026
Lead sponsor:
Agency:
Sir Run Run Shaw Hospital
Agency class:
Other
Source:
Sir Run Run Shaw Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06594692
