Trial Title:
Neoadjuvant Moderately Hypofractionated Radiotherapy Combined with Chemotherapy and Immunotherapy for High-risk LARC
NCT ID:
NCT06599827
Condition:
Rectal Cancer
Conditions: Official terms:
Rectal Neoplasms
Immunomodulating Agents
Conditions: Keywords:
Moderately Hypofractionated Radiotherapy
Immunotherapy
Locally Advanced Rectal Adenocarcinoma
Chemotherapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Patients will receive CapeOx chemotherapy, anti-PD-1 mAb immunotherapy, and moderately
hypofractionated radiotherapy.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
moderately hypofractionated radiotherapy
Description:
35 Gy in 10 fractions to mesorectal and metastatic lymph nodes, and 30 Gy in 10 fractions
to pelvic lymphatic drainage area, weekly over 5 days at 3-3.5 Gy/day.
Arm group label:
Experimental group
Intervention type:
Drug
Intervention name:
chemotherapy
Description:
CapeOx-Capecitabine 1000 mg/m² orally twice daily (days 1-14, every 21 days) +
Oxaliplatin 130 mg/m² IV (day 1, every 21 days).
Arm group label:
Experimental group
Intervention type:
Drug
Intervention name:
immunotherapy
Description:
Serplulimab 300 mg IV infusion on day 1 every 21 days.
Arm group label:
Experimental group
Intervention type:
Procedure
Intervention name:
Total mesorectal excision (TME) surgery
Description:
Total mesorectal excision (TME) surgery assessment post 3 cycles of chemotherapy and
immunotherapy; eligible patients undergo TME surgery.
Arm group label:
Experimental group
Summary:
This study aims to evaluate the effectiveness and safety of combining moderately
hypofractionated radiotherapy with chemotherapy and anti-PD-1 antibodies as a neoadjuvant
treatment for high-risk locally advanced rectal cancer.
Detailed description:
This study investigates a novel treatment approach involving moderately hypofractionated
radiotherapy (3-3.5Gy×10) combined with chemotherapy and immunotherapy for patients with
high-risk locally advanced rectal adenocarcinoma, aiming to optimize treatment efficacy
and patient outcomes.
Neoadjuvant chemoradiotherapy followed by total mesorectal excision (TME) is the standard
of care for locally advanced rectal cancer, improving surgical resection rates, local
control, and sphincter preservation. Conventional long-course radiotherapy is the
standard modality for neoadjuvant therapy, but it has drawbacks such as long treatment
duration, high cost, and prolonged preoperative waiting time. Short-course radiotherapy,
on the other hand, offers shorter treatment duration, lower cost, and shorter
preoperative waiting time, but it is associated with higher rates of local recurrence.
Immunotherapy has demonstrated promising anti-tumor activity in colorectal cancers with
deficient mismatch repair (dMMR) and/or microsatellite instability-high (MSI-H) status,
but its role in proficient mismatch repair (pMMR) and/or microsatellite stable (MSS)
colorectal cancers remains unclear. However, studies have shown that the combination of
chemoradiotherapy and immunotherapy can increase the pathologic complete response rate
compared to chemoradiotherapy alone, suggesting that radiotherapy may serve as a
stimulator of adaptive immunity and synergize with immunotherapy. Therefore, this study
aims to explore the following regimen: neoadjuvant moderately hypofractionated
radiotherapy at a dose of 3.5 Gy × 10 fractions to the tumors and 3 Gy × 10 fractions to
the pelvic lymph node drainage area, combined with chemotherapy (capecitabine and
oxaliplatin) and immunotherapy (Serplulimab).
This prospective, single-center, non-randomized Phase II trial is designed to explore the
efficacy and safety of the treatment regimen. Patients will receive CapeOx chemotherapy,
anti-PD-1 monoclonal antibody immunotherapy, and a course of moderately hypofractionated
radiotherapy. The trial protocol prioritizes safety monitoring and efficacy assessments
through standardized clinical and imaging evaluations.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥18 and ≤75 years.
2. MRI-confirmed rectal adenocarcinoma with the lower edge of the lesion ≤10cm from the
anal verge.
3. Immunohistochemistry confirms proficiency in DNA mismatch repair (pMMR), or genetic
testing confirms microsatellite instability-low (MSI-L) or microsatellite stable
(MSS) status.
4. Pelvic MRI showing one of the following high-risk factors: cT4a/b; N2; extramural
vascular invasion (EMVI+); mesorectal fascia involvement (MRF+); enlarged lateral
lymph nodes.
5. ECOG performance status of 0-1.
6. No prior surgery, radiotherapy, chemotherapy, or targeted therapy.
7. Tolerable to radiotherapy, chemotherapy, and immunotherapy with laboratory results:
WBC ≥4.0 × 10^9/L, platelets ≥100 × 10^9/L, hemoglobin ≥80g/L, ALT <2ULN, TB
<35μmol/L, Scr <1.5ULN or creatinine clearance rate ≥50mL/min, TSH
≤ULN (if abnormal, consider T3 and T4 levels; if T3 and T4 are normal, patients can
still be included).
8. Voluntary participation with signed informed consent.
Exclusion Criteria:
1. Distant metastases.
2. Stage I or II rectal cancer not requiring neoadjuvant therapy.
3. Severe cardiovascular, pulmonary, neurological, renal, gastrointestinal, or systemic
diseases.
4. Untreated chronic hepatitis B carrier with HBV DNA >500 IU/ml, HCV RNA
positive patients, except for inactive hepatitis B surface antigen carriers, stable
hepatitis B (HBV DNA <500 IU/ml), and cured hepatitis C patients.
5. History of active autoimmune diseases or potential relapse of autoimmune diseases.
6. Patients who received corticosteroids (equivalent to prednisone >10mg/day) or
other immunosuppressive therapy within 2 weeks prior to study drug administration.
7. History of thyroid dysfunction.
8. Severe chronic or active infections requiring systemic antifungal or antiviral
therapy, including tuberculosis.
9. Known allergy or hypersensitivity to multiple drugs.
10. History of pelvic radiation.
11. History of inflammatory bowel disease.
12. Unwillingness to participate or sign informed consent.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Zhongshan Hospital, Fudan University
Address:
City:
Shanghai
Zip:
200030
Country:
China
Contact:
Last name:
Genwen Chen, MD, PhD
Phone:
+86-15802123840
Email:
chengenwen@fudan.edu.cn
Start date:
September 20, 2024
Completion date:
September 20, 2029
Lead sponsor:
Agency:
Shanghai Zhongshan Hospital
Agency class:
Other
Source:
Shanghai Zhongshan Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06599827
