Trial Title:
Total Neoadjuvant Chemoradiotherapy Plus Anti-PD-1 in Subperitoneal Patients With Locally Advanced Rectal CancerPatients With Locally Advanced Rectal Cancer: A Prospective, Single Arm, Exploratory Study
NCT ID:
NCT05998122
Condition:
Locally Advanced Rectal Cancer
Total Neoadjuvant Treatment
Anti-PD-1
Conditions: Official terms:
Rectal Neoplasms
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Other
Intervention name:
nCRT → (CapeOX+Sintilimab)×6 → Surgery/W&W
Description:
Radiation: Long-course chemoradiotherapy is delivered in 50 Gy/25 fractions with
concurrent Capecitabine (825mg/m2, P.O. Bid, 5d/w).
Drug: CapeOX (Capecitabine 1000mg/m2, P.O. Bid, d1-d14, q3w; Oxaliplatin 130mg/m2, i.v.,
d1, q3w), and Sintilimab (200mg, i.v. , d1).
Surgical Approach: TME surgery, The surgical approach can be open, laparoscopic or
robotic depending on the patient.
Arm group label:
Experimental
Summary:
Previously, preliminary results, from a subgroup analysis of STARS-RC03 (NCT04906044)
conducted by our research team, showed that the 6-cycles consolidation chemotherapy
combining with anti-PD-1 therapy had a better tumor regression advantage with a
restricted safety profile contrasted with 3-cycle counterparts. Herein, we designed this
study to further evaluate the short-term efficacy (such as pCR rate, R0 resection rate,
etc.) and long-term survival (including DFS, OS, etc.) of 6-cycles consolidation therapy.
Detailed description:
The combination of total neoadjuvant treatment (TNT) and immunotherapy has shown a
significant improvement in the pCR rate compared to the standard of care (SOC) or TNT
alone for pMMR LARC. On this basis, we believe that this treatment mode will offers the
opportunity of organ preservation for subperitoneal "Bad" or "Advanced" patients with
LARC, who are initially assessed as unresectable or difficult to obtain R0 resection.
Previously, preliminary results, from a subgroup analysis of STARS-RC03 (NCT04906044)
conducted by our research team, showed that the 6-cycles consolidation chemotherapy
combining with anti-PD-1 therapy had a better tumor regression advantage with a
restricted safety profile contrasted with 3-cycle counterparts. Herein, we designed this
study to further evaluate the short-term efficacy (such as pCR rate, R0 resection rate,
etc.) and long-term survival (including DFS, OS, etc.) of 6-cycles consolidation therapy.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. The patients and their families are able to understand and are willing to
participate in this clinical study, and sign an informed consent form.
2. Age: 18~75 years old, no gender limit;
3. Pathologically diagnosed rectal adenocarcinoma: differentiated into Grade 1-3, that
is, high, medium, and poorly differentiated tubular adenocarcinoma; classified as
pMMR/MSS.
4. The initial TNM risk category (from Rectal cancer: ESMO Clinical Practice
Guidelines, 2017 edition) is as follows: 1) "Bad": cT3c/d or very low localisation
levators threatened, MRF clear; cT3c/d mid-rectum, cN1-N2 (extranodal), EMVI+,
limited cT4aN0; 2) "Advanced": cT3 with any MRF involved, any cT4a/b, lateral node+.
5. The lower edge of the tumor is located below the peritoneal reflex;
6. No distant transfer;
7. ECOG PS score 0-1 within 7 days before the first medication;
8. Hepatitis B Surface Antigen (HBsAg) (-) and Hepatitis B Core Antibody (HBcAb) (-).
If HBsAg (+) or HBcAb (+), hepatitis B virus deoxyribonucleic acid (HBV-DNA) must be
less than 1000 copies/mL or 200 IU/mL before entering the group.
9. HCV antibody (-)
10. The main organ function is normal.
11. No history of pelvic radiotherapy;
12. No history of rectal cancer surgery or chemotherapy;
13. Not accompanied by systemic infections requiring antibiotic treatment;
14. Heart, lung, liver, and kidney functions can tolerate surgery;
15. Others, based on the results of previous medical history, vital signs, physical
examination or laboratory examination, the research doctor judges that you are
suitable for participating in this clinical study.
Exclusion Criteria:
1. Recurrent rectal cancer;
2. Patients who are planning to undergo or have previously received organ or bone
marrow transplantation;
3. Myocardial infarction or poorly controlled arrhythmia (including QTc interval ≥ 450
ms for males and ≥ 470 ms for females) occurred within 6 months before the first
medication (QTc interval is calculated by Fridericia formula);
4. Existence of NYHA standard grade III to IV cardiac insufficiency or color Doppler
ultrasound examination: LVEF (left ventricular ejection fraction) <50%;
5. Human immunodeficiency virus (HIV) infection;
6. Suffer from active tuberculosis;
7. Past and present patients with interstitial pneumonia, pneumoconiosis, radiation
pneumonia, drug-related pneumonia, severely impaired lung function, etc., which may
interfere with the detection and treatment of suspected drug-related lung toxicity;
8. Patients with active or suspicious autoimmune disease, or with a history of that;
9. Received treatment with live vaccines within 28 days before the first
administration; except for inactivated viral vaccines for seasonal influenza;
10. Have received other antibody/drug treatments against immune checkpoints in the past,
such as PD-1, PD-L1, CTLA4, etc.;
11. Known to have a history of severe allergies to any monoclonal antibody or research
drug excipients;
12. In the past 5 years, patients have suffered from malignant tumors whose survival
rate is significantly lower than the historical data of our rectal cancer survival
rate (properly treated basal cell carcinoma, skin squamous cell carcinoma, small
kidney cancer, breast cancer, and papillary thyroid carcinoma are not included here.
range);
13. The patient has had arterial embolism diseases in the past 6 months, such as angina
pectoris, MI, TIA, CVA, etc.;
14. Have received other types of anti-tumor or experimental treatments;
15. The patient is a female during pregnancy or lactation;
16. The patient has other diseases or abnormal mental states, which may affect the
patient's participation in this study;
17. There are patients who may increase the risk of participating in research and
research medication, or other severe, acute and chronic diseases, who are not
suitable for clinical research based on the judgment of the investigator.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
First Hospital of Jilin University
Address:
City:
Changchun
Country:
China
Start date:
September 1, 2023
Completion date:
December 31, 2028
Lead sponsor:
Agency:
The First Hospital of Jilin University
Agency class:
Other
Source:
The First Hospital of Jilin University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05998122
