Neoadjuvant Therapy for Locally Advanced Colon Cancer

Phase 2

Completed

• Conditions: Colon Cancer; Neoadjuvant Therapy
• Interventions: Drug: Camrelizumab , apatinib and chemotherapy

• Registration Number: NCT04625803
• Lead Sponsor: Zhejiang University

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.

Study Timeline

• Study First Submitted: 2020-11-04
• Study First Submitted QC: 2020-11-09
• Study First Posted: 2020-11-12
• Study Start: 2021-01-04
• Primary Completion: 2023-09-30
• Study Completion: 2023-09-30
• Results First Submitted: 2024-10-26
• Status Verified: 2025-05
• Results First Submitted QC: 2025-05-30
• Last Update Submitted: 2025-05-30
• Results First Posted: 2025-06-17
• Last Update Posted: 2025-06-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 64

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
chemotherapy, PD-1 inhibitor and Apatinib	Camrelizumab , apatinib and chemotherapy	Participants received 5 preoperative cycles of PD-1 inhibitor and chemotherapy (mFOLFOX6), 2 months of apatinib, followed by surgery. Apatinib,PD-1 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.

Primary Outcome Measures

Name	Time	Method
Tumor Regression Rate of MSS/pMMR Patients	2 years	the percentage of tumor regression rate (2-4) in pMMR patients

Secondary Outcome Measures

Name	Time	Method
Pathologic Complete Response (pCR) Rates	2 years	Percentage of patients with pathological complete response
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
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%
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

Trial Locations

Locations (1)

First affiliated hospital, Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China