Raltitrexed-based Chemotherapy Plus Bevacizumab in Retreated Patients With Advanced Colorectal Cancer

Study Overview
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Brief Summary
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The objective is to investigate the efficacy and safety of raltitrexed-based chemotherapy plus bevacizumab in the treatment of advanced colorectal cancer

Official Title
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A Phase II Study of Raltitrexed-based Chemotherapy Plus Bevacizumab in Retreated Patients With Advanced Colorectal Cancer

Conditions
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Advanced Colorectal Cancer

Intervention / Treatment
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* Drug: Raltitrexed
* Drug: Irinotecan
* Drug: Oxaliplatin
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-70 years; histological and/or cytological confirmation of ACC; disease progression while on first-line palliative fluoropyrimidine-based chemotherapy or relapse within 6 months after adjuvant chemotherapy; at least one measurable objective tumor lesion by spiral CT examination, the maximum diameter ≥ 1cm（according to RECIST 1.1） ECOG performance status 0-1 life expectancy of at least 3 months satisfactory main organ function，laboratory test must meet the following criteria: hemoglobin (HGB) ≥90g/L, neutrophil count（ANC） ≥1.5×109/L, platelet count（PLT） ≥80×109/L, Serum creatinine（CR）≤1.5 upper normal limitation (UNL)，total bilirubin (TBil) ≤1.5 upper normal limitation (UNL), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 UNL (For patients with liver metastasis, the AST/ALT must be ≤5.0 UNL), Alkaline phosphatase（ALP）≤3 UNL(For patients with liver metastasis, the ALP must be ≤5.0 UNL); written informed consent Exclusion Criteria: prior exposure to raltitrexed; Clinically significant cardiovascular disease, for example symptomatic coronary artery disease, myocardial infarction (<=6 months before treatment start),congestive heart failure （New York Heart Association ，NYHA>= grade 3）,stroke or transient ischemic attack Accept kidney dialysis treatment now chronic enteropathy on unresolved bowel obstruction; previous malignant disease other than carcinoma in situ of the cervix or basal cell carcinoma of the skin; the UGT1A1 *28（7/7）*6（A/A） gene type; pregnant or lactated women; Unsuitable for the study or other chemotherapy determined by investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Raltitrexed and Irinotecan（RALIRI） plus Bevacizumab(AVASTIN)<br>Irinotecan:250mg/m2 iv,90min,d1, Raltitrexed:3.0mg/m2,iv,15min,d1, Bevacizumab:7.5mg/kg iv,30min,d1,q3w. Maintenance: Raltitrexed(3.0mg/m2,iv,15min,d1,q3w)+Bevacizumab(7.5 mg/kg q3w) | Drug: Raltitrexed<br>* Raltitrexed:3mg/m2,iv 15min,d1,q3w.<br>Drug: Irinotecan<br>* Irinotecan:250mg/m2,iv 90min,d1,q3w.<br>Drug: Bevacizumab<br>* Bevacizumab:75mg/kg,iv 30min,d1,q3w.<br>* Other names: Avastin;|
| Experimental: Raltitrexed and Oxaliplatin（RALOX） plus Bevacizumab(AVASTIN)<br>Oxaliplatin:130mg/m2 iv,120min,d1, Raltitrexed:3.0mg/m2,iv,15min,d1, Bevacizumab:7.5mg/kg iv,30min,d1,q3w. Maintenance: Raltitrexed(3.0mg/m2,iv,15min,d1,q3w)+Bevacizumab(7.5 mg/kg q3w) | Drug: Raltitrexed<br>* Raltitrexed:3mg/m2,iv 15min,d1,q3w.<br>Drug: Oxaliplatin<br>* Oxaliplatin:130mg/m2,iv 120min,d1,q3w.<br>Drug: Bevacizumab<br>* Bevacizumab:75mg/kg,iv 30min,d1,q3w.<br>* Other names: Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Progression Free Survival | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | Overall Survival | 15 months | 
| ORR | Objective Response Rate | 36 months | 
| DCR | Disease Control Rate | 36 months | 
| AEs | Percentage of participants experiencing grade 3-5 adverse events | 36 months |