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

Phase 2

• Conditions: Advanced Colorectal Cancer
• Interventions: Drug: Raltitrexed; Drug: Irinotecan; Drug: Oxaliplatin; Drug: Bevacizumab

• Registration Number: NCT03126071
• Lead Sponsor: Jiangsu Cancer Institute & Hospital

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2017-02-15
• Study First Submitted: 2017-04-20
• Study First Submitted QC: 2017-04-20
• Study First Posted: 2017-04-24
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-27
• Last Update Posted: 2021-08-30
• Primary Completion: 2022-08-15
• Study Completion: 2023-02-15

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Raltitrexed and Irinotecan（RALIRI） plus Bevacizumab(AVASTIN)	Raltitrexed	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)
Raltitrexed and Irinotecan（RALIRI） plus Bevacizumab(AVASTIN)	Irinotecan	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)
Raltitrexed and Oxaliplatin（RALOX） plus Bevacizumab(AVASTIN)	Raltitrexed	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)
Raltitrexed and Irinotecan（RALIRI） plus Bevacizumab(AVASTIN)	Bevacizumab	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)
Raltitrexed and Oxaliplatin（RALOX） plus Bevacizumab(AVASTIN)	Oxaliplatin	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)
Raltitrexed and Oxaliplatin（RALOX） plus Bevacizumab(AVASTIN)	Bevacizumab	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)

Primary Outcome Measures

Name	Time	Method
PFS	6 months	Progression Free Survival

Secondary Outcome Measures

Name	Time	Method
OS	15 months	Overall Survival
ORR	36 months	Objective Response Rate
DCR	36 months	Disease Control Rate
AEs	36 months	Percentage of participants experiencing grade 3-5 adverse events

Trial Locations

Locations (4)

Nantong Tumor Hospital; 🇨🇳 Nantong, Jiangsu, China

The First Affiliated Hospital of Soochow University; 🇨🇳 Suzhou, Jiangsu, China

Jiangsu Cancer Institute & Hospital; 🇨🇳 Nanjing, Jiangsu, China

Rui Jin Hospital Shanghai Jiao Tong University School of Medicine; 🇨🇳 Shanghai, Shanghai, China