Locally Advanced Rectal Cancer
Conditions
Keywords
pMMR/MSS, locally Advanced Rectal Cancer, PD-1, neoadjuvant, chemoradiation, Thymalfasin
Brief summary
This is an open, prospective, multi-center, single-arm phase II clinical study assessing the efficacy and safety of neoadjuvant chemoradiotherapy combined with PD-1 inhibitor and thymalfasin in patients with pMMR/MSS locally advanced middle and low rectal cancer.
Detailed description
This study is an open, prospective, multi-center, single-arm phase II clinical study. In this study, patients with pMMR/MSS locally advanced middle and low rectal cancer were selected as the subjects and treated with neoadjuvant treatment protocol of long-course concurrent chemoradiotherapy combined with PD-1 monoclonal antibody and thymalfasin. The primary endpoint of the study was complete response (CR) rate. The secondary end points included treatment-related adverse events (TRAEs) rate, 30-day incidence of postoperative complications, objective response rate (ORR), 3-year disease-free survival (DFS) rate, Neoadjuvant rectal cancer (NAR) score, R0 resection rate, and anal preservation rate.
Interventions
DRUGcapecitabine
825-1000mg/m2,po,bid
DRUGtislelizumab
200mg,iv.gtt,q3w
DRUGthymalfasin
4.8mg,sc,biw
RADIATIONlong-term radiotherapy
50 Gy/25 f, 2 Gy/day
Sponsors
Peking Union Medical College Hospital
Beijing Friendship Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
neoadjuvant chemoradiotherapy combined with PD-1 monoclonal antibody and thymalfasin
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patients who were fully informed of the study and voluntarily signed the informed consent form; 2. Patients with rectal cancers must satisfied all the following conditions: 1\) Stage II/III LARC (cT3-4aN0M0 and cT1-4aN1-2M0); 2) Tumor distal located ≤ 10 cm from anal verge (MRI diagnosed); 3) pMMR or MSS confirmed by immunohistochemistry or genetic test. 3.Patients regardless of gender with aged ≥18 years and ECOG score of 0 or 1; 4. Physical and viscera function of patients can withstand major abdominal surgery; 5.Patients are willing and able to follow the study protocol during the study 6.Patients give consent to the use of pathological specimens for study 7.Within 28 days prior to enrolment, we must confirm a negative serological pregnancy test for child-bearing age women and they agree to use effective contraception for the duration of drug use and for 60 days after the last dose.
Exclusion criteria
1. Patients have a present or previous active malignancy except the diagnosis of rectal cancer this time; 2. Patients underwent major surgery within 4 weeks prior to study treatment; 3. Patients have any condition affects the absorption of capecitabine through gastrointestinal tract; 4. Patients have severe uncontrolled recurrent infections, or other severe uncontrolled concomitant diseases; 5. Patients who are allergic to any of the ingredients under study; 6. Patients with severe concomitant diseases with estimated survival ≤ 5 years; 7. Patients with present or previous moderate or severe liver and kidney damage presently or previously; 8. Patients have received other study medications or any immunotherapy currently or in the past; 9. Patients preparing for or previously received organ or bone marrow transplant; 10. Patients who received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to the initiation of study therapy; 11. Patients with congenital or acquired immune deficiency (such as HIV infection); 12. If patients with a history of uncontrolled epilepsy, central nervous system disease or mental disorder, the investigator will determine whether the clinical severity prevents the signing of informed consent or affects the patient's oral medication compliance; 13. Patients with other factors that may affect the study results or cause the study to be terminated midway, such as alcoholism, drug abuse, other serious diseases (including mental illness) requiring combined treatment and severe laboratory examination abnormalities. 14. Pregnant or lactating women Criteria for Withdrawal: 1. The subject withdraws informed consent; 2. The subject requests to withdraw from the study, or loses follow-up; 3. The subject demonstrates poor compliance and is unable to participate in the treatment and visits as required by the study protocol; 4. The subject experiences intolerable adverse events, and the investigator determines that continuing the study may be detrimental to the subject; 5. Other reasons, where the investigator determines it is not suitable for the subject to continue in the study. Criteria for Study Termination: 1. There are major errors in the study protocol; 2. The study involves significant risks and is terminated following review by the ethics committee; 3. Termination requested by the sponsor or regulatory authorities.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CR rate | from preoperative to 10 days postoperative | complete response rate, If patients achieved cCR after neoadjuvant therapy or were confirmed pCR after TME, they were considered as complete response (CR). pCR was defined as no residual tumor cells on the histologic examination of surgical specimens according to AJCC 8th edition. cCR was defined according to the Memorial Sloan Kettering Cancer Center (MSKCC) standard. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 30-day incidence of postoperative complications | within 30 days after surgery | incidence of surgical complications within 30 days after surgery |
| ORR | before surgery | objective response rate; The ORR rate is the result of complete response (CR) rate plus partial response (PR) rate. |
| 3-y DFS rate | 3 years | 3-year disease free survival rate |
| NAR score | within 10 days after surgery | neoadjuvant rectal score |
| R0 resection rate | within 10 days after surgery | rate of R0 resection |
| anal preservation rate | instantly after surgery | proportion of patients with preserved anal sphincter |
| TRAE | from commencing of treatment to the 30th day after surgery | incidence of treatment-related adverse event |
Other
| Measure | Time frame | Description |
|---|---|---|
| The expression of CD163 | up to 3 months after surgery | The density, H-score of each marker in paraffin-embedded tissue sections detected by mIHC |
| The expression of CD4 | up to 3 months after surgery | The density, H-score of each marker in paraffin-embedded tissue sections detected by mIHC |
| The expression of CD8 | up to 3 months after surgery | The density, H-score of each marker in paraffin-embedded tissue sections detected by mIHC |
| The expression of CD86 | up to 3 months after surgery | The density, H-score of each marker in paraffin-embedded tissue sections detected by mIHC |
| The expression of CD68 | up to 3 months after surgery | The density, H-score of each marker in paraffin-embedded tissue sections detected by mIHC |
Countries
China
Outcome results
None listed