A Phase Ⅰb/Ⅱ Study of Fruquintinib Combined With Capecitabine in the First-line Maintenance Treatment of RAS/BRAF Wild-type Metastatic Colorectal Cancer
Overview
- Phase
- Phase 1
- Intervention
- fruquintinib plus capecitabine
- Conditions
- Metastatic Colorectal Cancer
- Sponsor
- Chinese Academy of Medical Sciences
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- recommended phase 2 dose (RP2D)
- Last Updated
- 3 years ago
Overview
Brief Summary
This phase I/II study was designed to evaluate the efficacy and safety of fruquintinib combination with capecitabine in maintenance treatment after first-line chemotherapy combined with cetuximab.
Detailed Description
At present, most studies use chemotherapy combined with cetuximab or cetuximab alone as the maintenance treatment scheme after the first-line regimen containing cetuximab. However, the skin reaction caused by cetuximab and frequent infusion treatment will bring inconvenience to patients. MACBETH study compared the maintenance of bevacizumab with cetuximab, although there was no significant difference in PFS between them, the Bev group seemed to convey a longer median OS. Fruquintinib is a highly selective anti angiogenesis TKI. This study aims to explore the efficacy and safety of fruquintinib combined with capecitabine in maintenance treatment after first-line chemotherapy combined with cetuximab. Both fruquintinib and capecitabine are orally given, so this regimen may provide a maintenance treatment option that is more manageable for patients in clinical practice.
Investigators
Lin Yang
Professor
Chinese Academy of Medical Sciences
Eligibility Criteria
Inclusion Criteria
- •Patients with histologically confirmed metastatic colorectal adenocarcinoma;
- •18-75 years old;
- •Eastern Cooperation Oncology Group (ECOG) performance score 0-1;
- •At least one evaluable lesion for disease assessment according to RECIST version 1.1;
- •Able to take oral medications;
- •Patient have achieved CR, PR or SD after up to 8 cycles of first-line standard FOLFOX / - FOLFIRI / XELOX / xeliri + cetuximab treatment, and remained unresectable;
- •If radiotherapy has been performed before enrollment, at least one lesion should be located outside the radiation field;
- •Adequate organ functions as assessed by the following laboratory requirements: Leukocytes≥3.0x10\^9/L, absolute neutrophil count≥1.5x10\^9/L, platelet count≥100x10\^9/L, hemoglobin≥9g/dL; serum bilirubin≤1.5x the upper limit of normal(ULN);Alanine aminotransferase(ALT) and aspartate aminotransferase(AST)≤2.5x ULN; serum creatinine≤1.5x ULN.
- •An expected survival of at least 12 weeks;
- •Fertile male or female patients volunteered to use effective contraceptive methods during the study period and within 6 months after the end of treatment;
Exclusion Criteria
- •Patients who have received fruquintinib;
- •Patients who have received TACE within 6 weeks before enrollment;
- •Participated in other unapproved or unlisted drug clinical trials in China within 4 weeks before enrollment, and received corresponding experimental drug treatment;
- •Patients with dysphagia, active peptic ulcer, intestinal obstruction, active gastrointestinal bleeding, peptic perforation, malabsorption syndrome or uncontrolled intestinal inflammatory diseases;
- •International normalized ratio (INR) \> 1.5 or partially activated prothrombin time (APTT) \> 1.5 × ULN；
- •The researchers judged clinically significant electrolyte abnormalities;
- •At present, the patient has hypertension that cannot be controlled by drugs, which is specified as: systolic blood pressure ≥ 140 mmHg and / or diastolic blood pressure ≥ 90 mmHg;
- •Patients currently have poorly controlled diabetes (fasting glucose level is greater than CTCAE grade 2 after regular treatment);
- •Have received any surgery or invasive treatment or operation within 4 weeks before enrollment (except venous catheterization, puncture and drainage, etc.);
- •Active or uncontrolled severe infection ≥ grade 2 according to National Cancer Institute Common Toxicity (NCI-CTC) criteria;
Arms & Interventions
Experimental
fruquintinib plus capecitabine
Intervention: fruquintinib plus capecitabine
Outcomes
Primary Outcomes
recommended phase 2 dose (RP2D)
Time Frame: up to 1 year
RP2D is determined according to DLT and MTD in the phase 1 study
progression-free survival (PFS)
Time Frame: up to 3 years
PFS is defined as the time from the start of maintenance treatment to the earliest evidence of disease progression (per RECIST v1.1), or death from any cause
Secondary Outcomes
- Adverse events (AEs)(up to 3 years)
- disease control rate (DCR)(up to 3 years)
- objective response rate (ORR)(up to 3 years)
- overall survival (OS)(up to 3 years)