A phase II trial of lenvatinib in patients with metastatic colorectal cancer after standard chemotherapy
- Conditions
- metastatic colorectal cancer
- Registration Number
- JPRN-jRCT1091220261
- Lead Sponsor
- ational Cancer Center HospitalDepartment of Gastrointestinal Medical OncologySatoru Iwasa
- Brief Summary
Two recent international phase 3 studies reported that regorafenib or trifluridine/tipiracil provided significant improvements in DCR, PFS and OS, compared with placebo, in patients with metastatic colorectal cancer after failure of standard chemotherapies (DCR; 41%, median PFS; 1.9 months, median OS; 6.4 months in the CORRECT study, and DCR; 44%, median PFS; 2.0 months, median OS; 7.1 months in the RECOURSE study). Interestingly, the present single-arm phase 2 study of lenvatinib revealed favorable DCR and median PFS values in patients with metastatic colorectal cancer, compared with those in the regorafenib or trifluridine/tipiracil study. The most common adverse events were hypertension, proteinuria, thrombocytopenia, and fatigue, while the most case of grade 2 or 3 hypertension and proteinuria required treatment interruption and dose reduction. Most patients with metastatic colorectal cancer in the salvage-line setting had grade 1 or 2 proteinuria and hypertension at baseline because of the long-term prior treatment with anti-VEGF/VEGFR treatment. Therefore, it was suggested that those adverse events and dose reductions were higher than those of trials for the other cancer. Although palmar-plantar erythrodysesthesia is a not life-threatening toxicity, these adverse events have a significant impact on treatment schedules and quality of life in treated patients. More than Grade 3 palmar-plantar erythrodysesthesia has been observed in 0% of patients treated with lenvatinib in this study, while 28% in patients treated with regorafenib in the CORRECT Japanese population. To date, the clear mechanism of palmar-plantar erythrodysesthesia by VEGF receptor tyrosine kinase inhibitors is not known, but it has been reproduced that palmar-plantar erythrodysesthesia by lenvatinib is well tolerated. Overall, it is suggested that lenvatinib might be a favorable treatment option in terms of toxicities.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 30
1)Pathologically proven colorectal adenocarcinoma
2)Unresectable metastatic colorectal cancer (except for appendiceal and anal canal cancer)
3)Refractory or intolerable to all of the following standard chemotherapy
a.Fluoropyrimidines,oxaliplatin,irinotecan and bevacizumab
b.Cetuximab or panitumumab in patients with RAS wild-type
c.TAS-102
4)No symptomatic brain metastasis and carcinomatous meningitis
5)Oral intake
6)Aged 20 to 79 years
7)Performance Status 0 or 1
8)One or more measurable lesions confirmed by contrast enhanced CT
9)No prior treatment of lenvatinib and regorafenib
10)Not received anti-cancer therapy within 14days before registration
11)Adequately controlled blood pressure
12)Not having any of the following histories/complications
a.History of hypertensive crisis or hypertensive encephalopathy
b.History of total gastrectomy
c.History of surgery under general anesthesia or laparotomy biopsy within 28days before registration
d.Unrecovered wound,active gastrointestinal ulcer or bleeding from the primary lesion
e.History of congenital hemorrhagic diathesis or coagulation disorder
f.Cardiovascular diseases requiring more than 325mg of aspirin daily
13)Adequate organ functions defined as below within 14days before registration
a.Neutrophil count >=1500/mm3
b.Platelet count >=100000/mm3
c.Hemoglobin >=8.5g/dL
d.Total bilirubin <=1.8mg/dL
e.AST(GOT)<=100U/L (<=150U/L with liver metastases)
f.ALT(GPT)<=100U/L (<=150U/L with liver metastases)
g.Creatinine <=1.5mg/dL
h.PT-INR <=1.5(<=3.0 in patients receiving any prophylactic anticoagulant agents)
i.Adequate proteinuria value defined
i)Negative or 1+ on urine dipstick testing
ii)When >2+ on urine dipstick testing, <=1g/24hr by 24hr urine collection
14)Given consent to contraception
15)Written informed consent
1)Active double cancer; synchronous or metachronous within 5years. Patients with carcinoma in situ are eligible
2)Infections requiring systemic therapy
3)Fever of >=38 degrees Celsius at the time of registration
4)Grade >=2 adverse reactions caused by prior therapy except any grade of alopecia and grade 2 peripheral neurotoxicity
5)Pregnant or breast-feeding women,or women suspected of being pregnant
6)Mental disease interfering taking part in the trial
7)Taking continuous systemic steroids and/or other immunosuppressive drugs(orally or intravenously)
8)HIV antibody positive
9)Interstitial pneumonia and/or pulmonary fibrosis and/or severe pulmonary emphysema diagnosed by chest CT imaging
10)History of any of the followings; unstable angina within 6 months before registration,heart attack,pulmonary embolism,deep vein thrombosis,brain bleeding,cerebral infarction,transient ischemic attacks within 6 months before registration and arterial thromboembolism
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Disease control rate
- Secondary Outcome Measures
Name Time Method 1) Adverse events, 2) Overall response rate, 3) Progression-free survival, 4) Overall survival