Colon Cancer, Neoadjuvant Therapy
Conditions
Keywords
colon cancer, camrelizumab, neoadjuvant therapy, chemotherapy, apatinib
Brief summary
To determine the Efficacy and Safety of camrelizumab and apatinib combined with chemotherapy (mFOLFOX6) for MSS/pMMR locally advanced colon cancer.
Detailed description
To determine the rate of tumor regression grade 2-4 at time of radical resection of MSS/pMMR colon cancer following neoadjuvant treatment.To determine the pathologic downstage rates at time of radical resection of colon cancer following neoadjuvant treatment, pathologic complete response (pCR) rates, R0 resection rate, 2 year Disease free survival, OS(overall survival) and adverse events, including perioperative complication and mortality rate. To determine the pathologic downstage rates and pCR rate of radical resection of MSI/dMMR colon cancer.
Interventions
DRUGCamrelizumab , apatinib and chemotherapy
Camrelizumab 200 mg, IV infusion on Days 1 each 14-day cycle Apatinib 250mg oral administration once a day, for two months mFOLFOX6 oxaliplatin 85 mg/m\^2 IV infusion on Day 1 of each14-day cycle. Fluorouracil: 400 mg/m2 as a bolus injection given after a two-hour leucovorin infusion at a dose of 400 mg/m2. The loading dose is then followed by a 46-hour 5-fluorouracil infusion of 2,400 mg/m2 via a pump programmed to provide a constant drug infusion rate.
Sponsors
Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
MSS/pMMR:Participants received 5 preoperative cycles of PD1 inhibitor and chemotherapy (mFOLFOX6), 2 months of apatinib, followed by surgery. Apatinib,PD1 inhibitor and chemotherapy needed to be stopped for 4-6 months before operation. 1 month after surgery, 7 cycles of mFOLFOX6 combined with PD-1 monoclonal antibody were performed as adjuvant therapy. MSI/dMMR:Participants received 5 preoperative cycles of PD1 inhibitor and 2 months of apatinib, followed by surgery. Apatinib,PD1 inhibitor needed to be stopped for 4-6 months before operation. 1 month after surgery, 7 cycles of PD-1 monoclonal antibody and apatinib were performed as adjuvant therapy.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years, ≤75 years 2. Histologically confirmed colon cancer ( tumor penetrated of muscularis propria depth ≥5mm of T3 , T4, N0-2, M0) without distant metastasis (AJCC 8th). 3. ECOG 0-1 4. Surgical treatment is planned after completion of neoadjuvant therapy 5. Patients can swallow pills normally 6. Expected overall survival ≥12 months 7. Blood routine: no blood transfusion or blood products usage within 14 days, G-CSF or other hematopoietic stimulator was not used. WBC counts \> 3000/µl，Absolute neutrophil count (ANC) ≥ 1500 cells/µl，Platelet count ≥ 100,000/µl，Hemoglobin ≥ 9.0 g/dL. 8. AST, ALT and alkaline phosphatase ≤ 2.5 times the upper limit of normal (ULN)，Serum bilirubin ≤ 1.5 x ULN，creatinine\<ULN 9. Prothrombin time (PT), international standard ratio (INR) ≤1.5 × ULN 10. Patients who have not received systemic chemotherapy or immunotherapy 11. Women of childbearing age must be willing to use adequate contraceptives during the study period of drug treatment; 12. Informed consent has been signed.
Exclusion criteria
1. Patients have received any prior systemic antitumor therapy; 2. Active bleeding within 3 months; Occurrence of arterial/venous thrombosis within 6 months; Hereditary or acquired bleeding (e.g., clotting dysfunction) or thrombotic tendencies; Full dose oral or injectable anticoagulants or thrombolytic drugs for therapeutic purposes are currently being used or have been used recently (10 days prior to the commencement of study treatment); Surgery (except for biopsy) was performed within 4 weeks prior to the study or the surgical incision was not fully healed; Aspirin (\> 325 mg/ day) or dipyridamole, ticlopidine, clopidogrel, and silotazole are currently being used or have recently been used (10 days prior to the study). 3. Systemic corticosteroids or other systemic immunosuppressive drugs were used within 2 weeks prior to treatment. Immunosuppressive drugs were started or expected to be used during the trial. Inhaled corticosteroids, physiologic replacement doses of glucocorticoids are allowed. 4. Certain or suspected distant metastases. 5. The patient has a history of autoimmune disease. 6. Serious uncontrolled systemic diseases, such as severe active infections; 7. A person is known to be infected with the immunodeficiency virus (HIV) or known to be HIV-positive; 8. Patients have suffered from other malignancies in the past 5 years except cervical carcinoma in situ or basal cell carcinoma of the skin 9. Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers (HBV DNA \>500 IU/mL) or active HCV carriers with HCV RNA can be detected. Remarks: Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B patients (HBV DNA \< 500 IU/mL) may be enrolled 10. Anti-infective therapy was not discontinued 14 days before the study; 11. A prior history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonia, and symptomatic interstitial lung disease or the presence of active pneumonia on a chest CT scan within 4 weeks prior to the study. 12. Patients have a history of intestinal obstruction within six months. Patients with incomplete obstruction syndrome of ileus at the time of initial diagnosis may be enrolled in the study if they have received definitive (surgical) treatment to resolve the symptoms, as assessed by the investigator. 13. Patients have non-resectable factors, including surgical contraindications 14. Patients Have high blood pressure that cannot be well controlled by antihypertensive medication (systolic ≥140 mmHg or diastolic ≥90 mmHg) 15. Urine routine indicated urinary protein ≥++ and confirmed 24-hour urinary protein \>1.0g; 16. Known to be allergic to any study drug; 17. Patients have participated in other drug clinical studies within 4 weeks before enrollment; 18. Lactating women 19. According to the judgment of the researcher, the patient may have other factors that may affect the results of the study or cause the study to be terminated, such as alcohol abuse, drug abuse, other serious diseases (including mental diseases) requiring combined treatment. Patients have severe laboratory abnormalities, which will affect the safety of the patient.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Regression Rate of MSS/pMMR Patients | 2 years | the percentage of tumor regression rate (2-4) in pMMR patients |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| R0 Resection Rate | 2 years | R0 resection accounted for the percentage of all surgical patients=100% |
| The Rate of 2 Year Disease Free Survival (DFS) | 2 years | Disease-free survival (DFS) is defined as the time from operation to recurrence of tumor or death. We will evaluate 2 year DFS is 100% |
| Overall Survival (OS) | 2 years | Refers to the time of death from enrollment to any cause |
| Pathologic Complete Response (pCR) Rates | 2 years | Percentage of patients with pathological complete response |
| Perioperative Complication Rate | 3 months | The complication rate of all patients during the period around the time of a surgical operation |
| Mortality Rate | 2 years | the ratio between deaths and all patients in the study during treatment |
| Event Free Survival (EFS) | 2 years | The period from the beginning of neoadjuvant therapy to the occurrence of any of the following events, whichever occurs first: tumor progression as assessed by RECIST 1.1; Tumor recurrence, including local recurrence or distant metastasis; Death from any cause; EFS=100% |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chemotherapy, PD-1 Inhibitor and Apatinib From January 2021 to September 2022, 12 patients were enrolled. Most (10 \[83.3%\] of 12) patients were female. There were 10 patients (83.3%) with right-sided colon cancer. 7(58.3%) had cT4 stage tumors, and all patients had positive lymph nodes on baseline radiographic assessment. 10 (83.3%) completed the planned cycles of neoadjuvant therapy. 1 patient received 3 cycles of neoadjuvant therapy as a serious adverse event and 1 patient received 2 cycles of neoadjuvant therapy as tumor perforation . Of the 12 patients, 11 underwent surgery, of whom R0 resection was performed and 1 refused | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Chemotherapy, PD-1 Inhibitor and Apatinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Clinical N stage cN0 | 0 Participants |
| Clinical N stage cN1 | 5 Participants |
| Clinical N stage cN2 | 7 Participants |
| Clinical T stage cT3 | 5 Participants |
| Clinical T stage cT4a | 5 Participants |
| Clinical T stage cT4b | 2 Participants |
| ECOG performance status 0 | 8 Participants |
| ECOG performance status 1 | 3 Participants |
| ECOG performance status 2 | 1 Participants |
| MMR status dMMR | 4 Participants |
| MMR status pMMR | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 8 / 12 |
| serious Total, serious adverse events | 10 / 12 |
Outcome results
Primary
Tumor Regression Rate of MSS/pMMR Patients
the percentage of tumor regression rate (2-4) in pMMR patients
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tumor Regression Grade Rate of pMMR Patients | Tumor Regression Rate of MSS/pMMR Patients | 7 Participants |
Secondary
Event Free Survival (EFS)
The period from the beginning of neoadjuvant therapy to the occurrence of any of the following events, whichever occurs first: tumor progression as assessed by RECIST 1.1; Tumor recurrence, including local recurrence or distant metastasis; Death from any cause; EFS=100%
Time frame: 2 years
Secondary
Mortality Rate
the ratio between deaths and all patients in the study during treatment
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tumor Regression Grade Rate of pMMR Patients | Mortality Rate | 0 Participants |
Secondary
Overall Survival (OS)
Refers to the time of death from enrollment to any cause
Time frame: 2 years
Secondary
Pathologic Complete Response (pCR) Rates
Percentage of patients with pathological complete response
Time frame: 2 years
Secondary
Perioperative Complication Rate
The complication rate of all patients during the period around the time of a surgical operation
Time frame: 3 months
Secondary
R0 Resection Rate
R0 resection accounted for the percentage of all surgical patients=100%
Time frame: 2 years
Secondary
The Rate of 2 Year Disease Free Survival (DFS)
Disease-free survival (DFS) is defined as the time from operation to recurrence of tumor or death. We will evaluate 2 year DFS is 100%
Time frame: 2 years