DMMR Colorectal Cancer, Anti PD-1, Immunotherapy
Conditions
Keywords
CRC
Brief summary
According to the cancer statistics in 2020, colorectal cancer (CRC) remains a major public health issue worldwide, representing the third common cancer (10%) and second leading cause of death (9.4%) with 5-year survival rate approaching 65%. Meanwhile, 28.8% of the newly diagnosed cases and 30.3% of the CRC-related death occurs in China. Among all the CRC, stage I-III account for 75%. For the standard management for non-late stage(stage I-III) CRC patients, surgery including the primary site and local lymph nodes dissection has been the most important one. But for the high-risk stage II and locally-advanced stage III CRC, neoadjuvant or adjuvant therapy such as chemotherapy and radiotherapy plays a vital role in preventing the residual cancer cells to relapse and spread to distant sites after surgery. For the past decades, immunotherapy like anti-PD-1 and anti-CTLA4 checkpoint inhibitor achieves great process in solid tumor treatment especially for late-stage CRC. And Pembrolizumab and Nivolumab has been proved for dMMR/MSI-H late-stage-CRC by FDA. Combination of Ipilimumab and Nivolumab has achieved great success among the early-stage-CRC in NICHE study. The investigators here to carry out a phase II clinical trial to explore the safety and effect of single anti-PD-1 (Tisleizumab-BGB-A317 ) neoadjuvant treatment for non-late stage CRC patients.
Interventions
200mg i.v. q3w
Sponsors
Sun Yat-sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Able to provide consents and agree to follow the trial requirement and assessment; * Age \>=18 * ECOG score: 0 or1 * Biopsy pathological diagnosis as MSI-H/dMMR( both IHC and PCR method required) * Measurable and assessible primary tumor sites according to RECIST 1.1 * Able to provide 22ml peripheral blood for assessment for ctDNA * With all organ function sufficient * No bowel obstruction or fistula * No previous chemotherapy, radiotherapy and immunotherapy accepted history * Distant metastasis excluded before surgery by CT scan * Contraception required for women for the whole enrollment time until 3 months after last dose of immunotherapy
Exclusion criteria
* self-autoimmune diseases history such as SLE * People who using the immune suppressor * Severe allergy to other mono-clone antibody * Cerebral metastasis which hasn't be managed yet * Hypertension(SBP\>140mmHg，DBP\>90mmHg) * Uncontrolled diabetes(FBG\>10mmol/L) * Accepted anti-PD-1 or anti-PD-L1 immunotherapy in the past * Uncontrolled heart diseases such as NYHA II heart failure, unstable angina , cardiac infarction in 1 year and arrhythmia * Systemic inflammation which needs whole body treatment * Urine routine: protein \>=++ or 24hr urine protein\>=1g * Innate or acquired immune deficiency like HIV and HBV * Enrolled in other clinical trial already * Confirmed as metastasis before the surgery * Other malignancies has been diagnosed before * Tuberculosis * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pathological complete regression rate | From enrollment to 1 year after surgery | Patients without noninvasive or focal-invasive residues or involved lymph nodes should be considered as having achieved pCR. The rate is these patients over the whole group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CR rate | From enrollment to 1 year after surgery | Patients with non-invasive or focal-invasive or involved lymph nodes which persists for 4 weeks after neoadjuvant immunotherapy. The rate of these patients over the whole group. |
| Major Pathological Response rate | From enrollment to 1 year after surgery | Rate of the patients who had focal invasive and residue tumor site which less than 10% both in primary tumors and all lymph nodes. |
| Disease free survival | From enrollment to 1 year after surgery | The time interval between the enrollment to the events such as relapse, distant metastasis and progressed occured. |
Countries
China
Contacts
Primary ContactGong Chen, Prof
Backup ContactRong-xin Zhang, Prof
Outcome results
None listed