A Trial of Hypofractionation Radiotherapy in Combination With Sintilimab，GM-CSF and Fruquintinib in Patients With MSS Metastatic Colorectal Carcinoma (mCRC)
Overview
- Phase
- Phase 2
- Intervention
- hypofractionation Radiotherapy
- Conditions
- Colorectal Neoplasms
- Sponsor
- The First Affiliated Hospital of Xiamen University
- Enrollment
- 71
- Locations
- 1
- Primary Endpoint
- Progression-free survival (PFS)
- Last Updated
- 4 years ago
Overview
Brief Summary
To evaluate the clinical efficacy and safety of hypofractionation radiotherapy combined with sintilimab，GM-CSF and Fruquintinib in Patients With MSS Metastatic Colorectal Carcinoma (mCRC)
Detailed Description
Condition or disease:MSS Metastatic Colorectal Carcinoma (mCRC) Phase:Phase 2 Intervention/treatment: Radiation: hypofractionation radiotherapy Drug: sintilimab, GM-CSF , Fruquintinib
Investigators
Eligibility Criteria
Inclusion Criteria
- •Assigned informed consent
- •Age: 18-80 years
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-3
- •Histological or cytological documentation of adenocarcinoma of the colon or rectum MSS metastatic colorectal cancer(CRC) checked by IHC or PCR.
- •Patients must have failed at least two lines of prior treatment
- •Patients must have not previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody, anti-cytotoxic T lymphocyte-associated antigen 4 (cytotoxic T-lymphocyte-associated Protein 4, CTLA-4) antibody or other drug/antibody that acts on T cell costimulation or checkpoint pathways.
- •Patients must have not previously received Fruquintinib.
- •Life expectancy of at least 3 months
- •At least 1 measurable disease according to Response Evaluation Criteria in Solid --Tumors (RECIST) criteria, version 1.1.is necessary.
- •Controlled hypertension.
Exclusion Criteria
- •Patients with MSI-H / dMMR metastatic colorectal cancer(CRC);
- •Uncontrollable malignant pleural effusion, ascites or pericardial effusion (defined as ineffectively controlled by diuresis or puncture drainage judged by investigators);
- •Clinically significant abnormal electrolyte abnormality as judged by investigators;
- •Clinically significant liver disease, including active viral hepatitis \[HBsAg and/or HbcAb is positive and HBV (hepatitis B virus) DNA \> 10000 copies/ mL or \> 2000 IU/mL; HCV (hepatitis C virus) antibody positive and HCV RNA \> 1000 copies/ mL\], or other active hepatitis, clinically significant moderate to severe cirrhosis;
- •Central nervous system (CNS) metastasis in previous or screening is excluded ,except CNS without clinical symptom or stable period ≥4 weeks after treatment ;
- •Patients with evidence or history of propensity to hemorrhage within 3 months prior to first dosing, regardless of severity(such as melena, hematemesis, hemoptysis, bloody stools）；
- •History of arterial thrombosis within 6 months; Patients with history of deep vein thrombosis (DVT) are eligible as long as they have received or are receiving appropriate anticoagulation therapy.
- •Uncontrolled hypertension. (Systolic blood pressure 150 mmHg or diastolic pressure 90 mmHg despite optimal medical management).
- •Radical radiotherapy within 4 weeks prior to first dosing;
- •Patients have dysphagia;
Arms & Interventions
Experimental Group
hypofractionation radiotherapy combined with sintilimab,GM-CSF and Fruquintinib in the third-line or above treatment of MSS Metastatic Colorectal Carcinoma(mCRC)
Intervention: hypofractionation Radiotherapy
Experimental Group
hypofractionation radiotherapy combined with sintilimab,GM-CSF and Fruquintinib in the third-line or above treatment of MSS Metastatic Colorectal Carcinoma(mCRC)
Intervention: sintilimab
Experimental Group
hypofractionation radiotherapy combined with sintilimab,GM-CSF and Fruquintinib in the third-line or above treatment of MSS Metastatic Colorectal Carcinoma(mCRC)
Intervention: GM-CSF
Experimental Group
hypofractionation radiotherapy combined with sintilimab,GM-CSF and Fruquintinib in the third-line or above treatment of MSS Metastatic Colorectal Carcinoma(mCRC)
Intervention: Fruquintinib
Outcomes
Primary Outcomes
Progression-free survival (PFS)
Time Frame: 2 years
Defined as the time from the date of the first dose of treatment to the date of the first documentation of disease progression or death, whichever occurs first. Progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumours (RECIST) version. 1.1, and immune-related (ir) RECIST
Secondary Outcomes
- Duration of Response(DOR)(1 year)
- Overall survival (OS)(2 years)
- Safety:Percentage of Participants With Adverse Events (AEs)(Up to 30 days after the last cycle of per-protocol treatment and 90 days after last dose of treatment)
- Objective response rate(1 year)
- Disease Control Rate（DCR）(1 year)