Neoadjuvant Therapy for Locally Advanced Colon Cancer

Colon Cancer Clinical Trial

Official title:

Camrelizumab and Apatinib Combined With Chemotherapy (mFOLFOX6) in Neoadjuvant Therapy for Locally Advanced Colon Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04625803
• Other study ID #: AMBITION
• Status: Recruiting
• Phase: Phase 2
• Start date: January 4, 2021
• Est. completion date: November 30, 2025

Study information

• Verified date: July 2023
• Source: Zhejiang University
• Contact: Weijia Fang
• Phone: +86-571-87235147
• Email: weijiafang[@]zju.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To determine the Efficacy and Safety of camrelizumab and apatinib combined with chemotherapy (mFOLFOX6) for MSS/pMMR locally advanced colon cancer.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: November 30, 2025
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Colon Cancer
• Colonic Neoplasms
• Neoadjuvant Therapy

Intervention

Drug:
• Camrelizumab , 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.

Locations

Country	Name	City	State
China	First affiliated hospital, Zhejiang University	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor regression rate of MSS/pMMR patients	Tumor regression rate (TRG) was evaluated by pathologist, using Dworak criteria. The percentage of TRG 2,3,4 to all person will be evaluated at time of radical resection of colon cancer following neoadjuvant treatment. Grade 0: no regression, Grade 1: dominant tumor mass with obvious fibrosis and/or vasculopathy; Grade 2: dominantly fibrotic changes with few tumor cells or groups (easy to find); Grade 3: very few (difficult to find microscopically) tumor cells in fibrotic tissue with or without mucous substance; Grade 4: no tumor cells, only fibrotic mass (total regression or response)	3 months
Secondary	pathologic complete response (pCR) rates	Percentage of patients with pathological complete response assessed based on Dworak criteria	3 months
Secondary	R0 resection rate	R0 resection accounted for the percentage of all surgical patients	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.	2 years
Secondary	overall survival (OS)	Refers to the time of death from enrollment to any cause	2 years
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;	2 years
Secondary	perioperative complication rate	The complication rate of all patients during the period around the time of a surgical operation	3 months
Secondary	mortality rate	the ratio between deaths and all patients in the study during treatment	6 months