Neoadjuvant Therapy for Locally Advanced Colon Cancer

Sponsor

Zhejiang University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04625803

Collaborator

(none)

Enrollment

Location

Arm

58.8

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Colon Cancer Neoadjuvant Therapy	Drug: Camrelizumab , apatinib and chemotherapy	Phase 2

Detailed Description

To determine the rate of tumor regression grade 2-4 at time of radical resection of 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

64 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

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.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.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 4, 2021

Anticipated Primary Completion Date :

Nov 30, 2022

Anticipated Study Completion Date :

Nov 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: chemotherapy, PD-1 inhibitor and Apatinib 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.	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.

Arm

Intervention/Treatment

Experimental: chemotherapy, PD-1 inhibitor and Apatinib

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.

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.

Outcome Measures

Primary Outcome Measures

Tumor regression rate [3 months]
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)

Secondary Outcome Measures

pathologic complete response (pCR) rates [3 months]
Percentage of patients with pathological complete response assessed based on Dworak criteria
R0 resection rate [2 years]
R0 resection accounted for the percentage of all surgical patients
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.
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;
perioperative complication rate [3 months]
The complication rate of all patients during the period around the time of a surgical operation
mortality rate [6 months]
the ratio between deaths and all patients in the study during treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years, ≤75 years
Histologically confirmed colon cancer (cT4N0-2M0) without distant metastasis (AJCC 8th).
ECOG 0-1
Surgical treatment is planned after completion of neoadjuvant therapy
Right colon cancer (including ileocecal area, ascending colon, transverse colon to splenic flexion)
Patients can swallow pills normally
Expected overall survival ≥12 months
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.
AST, ALT and alkaline phosphatase ≤ 2.5 times the upper limit of normal (ULN)，Serum bilirubin ≤ 1.5 x ULN，creatinine<ULN
Prothrombin time (PT), international standard ratio (INR) ≤1.5 × ULN
Patients who have not received systemic chemotherapy or immunotherapy
Women of childbearing age must be willing to use adequate contraceptives during the study period of drug treatment;
Informed consent has been signed.

Exclusion Criteria:

Patients have received any prior systemic antitumor therapy;
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).
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.
Certain or suspected distant metastases.
The patient has a history of autoimmune disease.
Serious uncontrolled systemic diseases, such as severe active infections;
A person is known to be infected with the immunodeficiency virus (HIV) or known to be HIV-positive;
Patients have suffered from other malignancies in the past 5 years except cervical carcinoma in situ or basal cell carcinoma of the skin
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

Anti-infective therapy was not discontinued 14 days before the study;
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.
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.
Patients have non-resectable factors, including surgical contraindications
Patients Have high blood pressure that cannot be well controlled by antihypertensive medication (systolic ≥140 mmHg or diastolic ≥90 mmHg)
Urine routine indicated urinary protein ≥++ and confirmed 24-hour urinary protein

1.0g;

Known to be allergic to any study drug;
Patients have participated in other drug clinical studies within 4 weeks before enrollment;
Lactating women
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.